The Instituto Gulbenkian de Ciência (IGC) is an international biomedical research and graduate training institute, founded and supported by the Calouste Gulbenkian Foundation, in Portugal. This Annual Report covers the Instituto Gulbenkian de Ciência’s financial year, from 1st January to 31st December 2010.
COVER IMAGE Scanning electron microscope Image of a Drosophila erecta egg, showing the two appendages, with flat ends
BARBARA VREEDE (Evolutin and Development Group)
CONTENTS 05 06 12 14
ORGANISATION 82 83 84
ORGANISATION THE DIRECTOR'S INTRODUCTION THE IGC AT A GLANCE RESEARCH GROUPS 15 16 17 18 19 21 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 50 51 52 54 55 56 57
Protein-Nucleic Acids Interactions − ALEKOS ATHANASIADIS Plant Stress Signalling - ELENA BAENA GONZÁLEZ Meiosis and Development − VÍTOR BARBOSA Epigenetics and Soma - VASCO BARRETO Variation: Development and Selection − PATRÍCIA BELDADE Cell Cycle Regulation - MÓNICA BETTENCOURT DIAS Quantitative Organism Biology − JORGE CARNEIRO Molecular Neurobiology - DIOGO CASTRO Population and Conservation Genetics - LOUNÈS CHIKHI Neurobiology of Action - RUI COSTA Lymphocyte Physiology - JOCELYNE DEMENGEOT Plant Molecular Biology - PAULA DUQUE Plant Development - JOSÉ FEIJÓ Yeast Stress - LISETE FERNANDES Telomeres and Genome Stability - MIGUEL GODINHO FERREIRA Collective Dynamics - GABRIELA GOMES Evolutionary Biology - ISABEL GORDO Actin Dynamics - FLORENCE JANODY Epigenetic Mechanisms - LARS JANSEN Tissue Morphogenesis - MATHIAS KOEPPEN Organogenesis - JOAQUÍN RODRÍGUEZ LÉON Systems Neuroscience - ZACHARY MAINEN Patterning and Morphogenesis - MOISES MALLO Early Fly Development - RUI GONÇALO MARTINHO Development, Evolution and the Environment - CHRISTEN MIRTH Behavioural Neuroscience - MARTA MOITA Animal Behaviour - RUI OLIVEIRA Infection and Immunity - MICHAEL PARKHOUSE Disease Genetics - CARLOS PENHA GONÇALVES Computational Genomics - JOSÉ PEREIRA LEAL Behaviour and Metabolism - CARLOS RIBEIRO Complex Adaptive Systems and Computational Biology - LUÍS ROCHA Membrane Traffic in Disease and Novel Therapies - MIGUEL SEABRA Inflammation - MIGUEL SOARES Evolution and Development - ÉLIO SUCENA Host-microorganism Interactions - LUÍS TEIXEIRA Evolutionary Genetics - HENRIQUE TEOTÓNIO Innate Behaviour - MARIA LUÍSA VASCONCELOS Bacterial Signalling - KARINA XAVIER
58 RESEARCH FELLOWS 59 61 62 63 64 65 66 68
Plant Genomics - JÖRG BECKER Network Modelling - CLAUDINE CHAOUYIA Lupus and Autoreactive Immune Repertoire - CONSTANTIN FESEL Neuronal Structure and Function - INBAL ISRAELY Neuroethology Laboratory - SUSANA LIMA Antigen presentation and T cell activation - ELISABETTA PADOVAN Dopamine in Action Learning - JOSEPH PATON Cardiac Regeneration - LUIS ROSÁRIO
69 EXTERNAL GROUPS 70 FACILITIES AND SERVICES 71 73 74 75 76 78 79 80 81
Animal Facilities Transgenics Facility Plant Facility Cell Imaging Unit Genotyping and Sequencing Unit Gene Expression Unit Histology Unit Ion Dynamics Facility Bioinformatics and Computational Biology Unit
85 86
87 92 104 106 107
Portuguese Bioinformatics Centre Research Funding Affairs Innovation and Technology Office Informatics Library Equipment Purchasing and Maintenance Ethics Committee Administration and Accounts
RESEARCH STRUCTURES PUBLICATIONS AWARDS AND HONOURS MAJOR FUNDING SOURCES GRADUATE TRAINING AND EDUCATION
108 110 111 113 115
PhD Programme in Integrative Biomedical Sciences (PIBS) PhD Programme in Computational Biology (PDBC) Gulbenkian/Champalimaud International Neuroscience Doctoral Programme (INDP) Programme for Advanced Medical Research - Doctoral Programme for Physicians GTPB – The Gulbenkian Training Programme in Bioinformatics
117 THESES 119 SEMINARS, WORKSHOPS AND MEETINGS 149 PUBLIC ENGAGEMENT IN SCIENCE 150 155
Science Communication and Outreach Fundraising
CALOUSTE GULBENKIAN FOUNDATION The Calouste Gulbenkian Foundation is a Portuguese private institution of general public utility established by a clause in Calouste Sarkis Gulbenkian's will, in 1953. The purposes of the Foundation are charitable, artistic, educational and scientific. BOARD OF TRUSTEES EMÍLIO RUI VILAR Chairman MIKHAEL ESSAYAN Honoraray Chairman DIOGO DE LUCENA Trustee EDUARDO MARÇAL GRILO Trustee ISABEL MOTA Trustee MARTIN ESSAYAN Trustee TERESA GOUVEIA Trustee ANDRÉ GONÇALVES PEREIRA Non-executive Trustee ARTUR SANTOS SILVA Non-executive Trustee EDUARDO LOURENÇO Non-executive Trustee
158 ACKNOWLEDGEMENTS
INSTITUTO GULBENKIAN DE CIÊNCIA SCIENTIFIC ADVISORY BOARD The Scientific Advisory Board of the IGC oversees the scientific progress, graduate programmes, recruitment and overall performance of staff and research groups. The Scientific Advisory Board also advises the Board of the Calouste Gulbenkian Foundation on all matters of relevance to the mission of the Institute. SYDNEY BRENNER (The Salk Institute, USA) Chairman JONATHAN HOWARD (University of Cologne, Germany) MARTIN RAFF (University College London, UK) GINÉS MORATA (Universidad Autónoma de Madrid, Spain) NICOLE LE DOUARIN (Academie des Sciences, France) DAVID SABATINI (New York University, USA) KAI SIMONS (Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany) SUSUMU TONEGAWA (Massachusetts Institute of Technology, USA) RICHARD AXEL (Columbia University, USA) JEAN−PIERRE CHANGEUX (Pasteur Institute, France) TERRENCE SEJNOWSKY (The Salk Institute, USA) IGC DIRECTOR ANTÓNIO COUTINHO IGC DEPUTY DIRECTOR JOSÉ MÁRIO LEITE DEPUTY TO THE DIRECTOR JOCELYNE DEMENGEOT
THE DIRECTOR'S INTRODUCTION of “science” and “fellowships” “must be intimate and constant”, concluding that “the Foundation must choose to give its fellowships with the principal goal of preparing and improving [its own Institute’s] personnel”. On the basis of the Scientific Council report, the Foundation’s Board underlines the wish that “the IGC maintains - just like the Foundation, of which it represents the scientific expression - an international character, attracting to Portugal foreign investigators and stimulating young Portuguese scientists by confronting them with those”. Justifying the decision to create the IGC, the President writes “the creation of scientific institutions with an international character constitutes, by itself, the highest contribution to establish in Portugal the necessary conditions for an authentic scientific life, and thus contribute to its development.” While commenting on the Council’s reports, the Science Sector of the Foundation adds interesting perspectives, cited in the President’s report. It defends “fundamental research”, arguing that “all new knowledge has, sooner or later, practical applications, and fundamental research contributes the dominant part for progress in industrial production”, and suggesting the principle of “creating research laboratories around investigators, rather than predefined programmes”.
This year (2011) the Instituto Gulbenkian de Ciência (IGC) celebrates 50 years since its foundation by the Board of Administration of the Fundação Calouste Gulbenkian (FCG) on July 19, 1961. For us, scientists, this is a fitting date to celebrate, as the Institute has been the principal instrument for the Foundation’s intervention in science, one of its four statutory goals. It seems appropriate that this Introduction, rather than referring to the past year at the Institute, should contemplate its foundations and summarise what the Foundation has achieved with the IGC in this half a century.
With the decision of starting the IGC, the Foundation’s Board of Administration defined that it should “foster scientific research... [and] install [its] practice as a permanent and full-time activity, ensuring the necessary means, equipments and salaries; facilitate the presence at the Institute of university students and graduates, through the attribution of research fellowships; collaborate with Universities and other public organisms, whenever it would be deemed possible and desirable”. This wording provides a rather impressive picture of the state of development (or lack of it) of local scientific research in the 1960’s. On the other hand, it underscores the two major contributions of the IGC to science in Portugal: first, to professionalise research careers; second, to create graduate education in the country. In many ways, though in distinct forms and using alternative approaches, the IGC continues to follow those objectives: to provide scientists with the best working conditions, materially and intellectually, so that they can produce excellent science; to offer graduate students the possibilities to strive in their education with the best conditions worldwide.
A BIT OF IGC HISTORY Recently, on the occasion of the 50th anniversary of the Foundation, Jorge Calado very competently reviewed the history of science at the Foundation, including the IGC. I would not be able to add anything of relevance to it, except a biased personal view. Yet, it is an appropriate occasion to consider how the Institute’s history and evolution relates to its current aims and operation. Surprisingly, perhaps, it is impressive that today’s IGC continues to serve the Foundation’s missions and policies in ways that are very close, almost fully coincidental, to those originally defined, 50 years ago. The first thing to emphasise, as I have done in a previous Annual Report, is the vision, clairvoyance and modernity of the arguments that led to the Board’s decision to create the IGC. The writings of Azeredo Perdigão, the first President of the Foundation, and the reports of the first Scientific Council at the Foundation, are very much worth reviewing. As always, visionary and excellent policies are durable. In the deservedly famous President’s Report from 1959, Perdigão writes: “... [a] scientific and technical programme is a sine qua non condition of our economic and social progress”, and after citing Eisenhower’s sentence that “it is essential to give high priority to fundamental research...”, he points out the “priority of fundamental and uninterested scientific areas” [emphasis in the original], and continues to say that “in science... we must give the greatest freedom to the initiative and the creative power of individuals”.
The vision, clairvoyance and modernity of the arguments that led to the Board’s decision to create the IGC.
IGC ANNUAL REPORT ‘10
The IGC continues to follow those objectives: to provide scientists with the best working conditions, materially and intellectually, so that they can produce excellent science; to offer graduate students the possibilities to strive in their education with the best conditions worldwide.
What local science would have been, would it not have counted on the IGC’s contribution, is a perilous exercise, for it is well known that History is not compatible with “controlled experiments”. Yet, I would think there is general agreement that the achievements have been tremendously relevant: Portuguese biomedical scientists of several generations (who completed a University degree from 1969 to 1985) have been introduced to serious science through the courses of the Oeiras Advanced Studies; for many years, the IGC was essentially the only place in the whole country where fully dedicated scientists conducted research in autonomy, for the sake of science. Moreover, many a science department at various Universities and research institutions in Portugal are now home to scientists who are IGC alumni, let alone the hundreds of those educated under IGC responsibility, now working throughout the country. THE IMPACT OF IGC RESEARCH AND EDUCATION It is pertinent to ask what returns the FCG has had for its investments in the IGC. While other missions enrich the activity of the Institute, it was created to produce science and to promote science education and training. Hence, the corresponding returns may be measured by the number and impact of both its scientific publications and its graduates. The scientific databases list over 1,500 international publications with the IGC address, which have been cited more than 25,000 times in the relevant world literature. Around 1,100 of IGC publications were original articles, describing primary results produced here; on average, each of these has been cited in 20 other publications. In other words, work done at the IGC has significantly contributed to the advancement of science worldwide. As science is a collective enterprise that aims at the full understanding of the world, the Institute has contributed to a most noble cause; in the words of C.G.J. Jacobi, “le but unique de la science est l’honneur de l’esprit humain”.
The 1962 President’s report, written after the Board’s decision to create the IGC, makes abundant use of the advice given to the Foundation by its Scientific Council, notably that “...however numerous and large available resources may be, they should be... concentrated in pursuit of precise objectives that may then be more reproductive... and better correspond to the importance of the Foundation”. The Council defines science as “all forms of rational knowledge” and “scientific research as all the work that makes science progress”, and ascertains that “science is devoted to satisfying the most noble curiosities of the human spirit, a collective enterprise in which all civilised people participate”, defending that “no priorities should be established in any scientific domain, for reasons of the respective technological applications being more evident or short-termed”. While recognising that using science to promote social progress and education is the goal of other sectors at the Foundation, the Council concludes that the “relationships” between the Foundation’s sectors
THE DIRECTOR'S INTRODUCTION
All of us who embody today’s IGC are proud of these beginnings, and will strive to keep the Institute well in line with the initial principles and goals.
Nearly all goals and decisions of the Foundation’s Board were implemented and turned out most appropriate and effective. We, scientists, are deeply indebted to all those who took such decisions. Moreover, all of us who embody today’s IGC are proud of these beginnings, and will strive to keep the Institute well in line with the initial principles and goals.
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The scientific databases list over 1,500 international publications with the IGC address, which have been cited more than 25,000 times in the relevant world literature.
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Education, particularly if science-based, is the safest of all investments for a better world. Also here, the return for the Foundation is clear: already in 1969, the IGC introduced graduate education in Portugal, and generations of students initiated here their commitment to science. In 1993, the IGC launched the Gulbenkian Doctoral Programme in Biology and Medicine, which, incidentally, was the first of all Programmes at the Foundation, and the first 4-year graduate programme in this country. Throughout the last 17 years, the IGC has been responsible for a handful of other graduate programmes that today are known all over the world, and often used as example of innovation and excellence. More importantly, the Institute has since educated over 500 PhD candidates, and the “Gulbenkian students” have gained an exceptional reputation of excellence in many laboratories in Europe and the USA. In doing all this, the Institute has had a unique contribution to increasing the international reputation of the Foundation and to perpetuating the founder’s name.
The Institute has since educated over 500 PhD candidates, and the “Gulbenkian students” have gained an exceptional reputation of excellence in many laboratories in Europe and the USA.
TODAY’S IGC At the time of the celebration of the “round number anniversary”, it is, perhaps, also appropriate to assess current IGC contributions and to evaluate how close they are to the original institutional goals, as they were set 50 years ago. In the last 10 years alone, the Institute has produced more publications and original research articles than in the previous 40 years of its history, with no increased costs for the Foundation. In 2010, the number of other publications worldwide that have cited work done at the IGC reached 3,500, representing nearly 15% of all accumulated citations in its history.
In 2010, the number of other publications worldwide that have cited work done at the IGC reached 3,500, representing nearly 15% of all accumulated citations in its history.
The IGC has contributed to the scientific production in Portugal in a very unique manner, most particularly amongst the top tier journals1. Considering articles reporting primary scientific production (thus excluding opinion papers, reviews, letters to Editors, abstracts and the like) with an address in Portugal, the Institute has over the last 10 and 5 years, respectively, published 17 and 20% of all papers in Nature, and 16 and 23% of those in Science, in all areas of research! Analysing the areas that are well represented at the IGC (Cell Biology, Genetics, Immunology, and Neuroscience), the Institute is responsible for over one third (34 and 36%) of all articles with an address in Portugal in the four respective Nature journals, while these values reach 71 and 50% for publications in Nature Medicine. Though with smaller numbers, IGC contributions over the last 10 years, in other major journals in biomedical sciences, are also impressive: 50% of those in Cell, 36% of those in The Journal of Experimental Medicine, 43% of those in Developmental Cell, and 63% in Development. Moreover, in the majority of cases, the corresponding author of IGC-addressed articles was in Portugal - something rare amongst other publications in such journals, which are often multi-centre. These figures are far above the quantitative weight of the Institute in national science, both in terms of number of investigators and financing, and demonstrate that the excellence of IGC research is second to none in Portugal. CONTRIBUTION OF IGC RESEARCH TO PUBLICATIONS IN THE TOP 1% OF ALL JOURNALS IN THE ISI DATABASES (IN PERCENT OF ALL ARTICLES2 WITH AN ADDRESS IN PORTUGAL)
It is my conviction, however, that beyond publications and doctoral theses, the most important contribution of the IGC to Portuguese science in recent times relates to the new dynamics that the Institute introduced in the local scientific community and institutions. The IGC has been fighting institutional “closure”, “civil serviceness” of scientists, inbreeding, and ownership of individuals; it has promoted turnover and mobility in the community, established full scientific and financial autonomy of young investigators, as well as the responsibilities of institutions in terms of facilities and services. All these crucial aspects have dramatically changed over the last 10 years in Portugal, and I would like to think that the IGC example contributed to that evolution.
Source: Web of Science, March 2011
The most important contribution of the IGC to Portuguese science in recent times relates to the new dynamics that the Institute introduced in the local scientific community and institutions.
In 2011, the IGC was once again ranked by “The Scientist-Faculty of 1,000”, in the “10 Top Places” for young scientists (post-docs) to work outside the USA, for the second consecutive year. The Institute hosts more scientists, technicians and students than ever before, from a diversity of origins, as to their education and background, including geography: currently the IGC community includes people from 30 different countries around the world. We are all indebted to the Board of Administration of the Gulbenkian Foundation for the continued support, financially and otherwise, that the Institute has been privileged to receive. The Foundation provides the IGC with 5 M€/year, which allows the Institute to maintain its basic needs of operation, run facilities and PhD programmes, keep its intellectual life going. The total expenditure at the IGC in 2010, however, reached some 17.5 M€, including 2.5 M€ for the Champalimaud’s Neuroscience Programme at the IGC, 4.3 M€ in external salaries and fellowships, as well as nearly 6 M€ in competitive grants that were attracted thanks to the excellent work
The research groups at the Institute, beyond contributing the scientific and human excellence upon which the Gulbenkian Institute’s reputation is built, also provide a significant fraction of the costs involved in running the IGC, and should be acknowledged for that.
1 The journals with the highest “impact factor” in the Journal Citation Reports database in the Web of Science
(ISI), representing less than 1% of all scientific journals. 2 Excluding
Source: Web of Science, March 2011
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opinion papers, editorials, reviews, letters to editors, abstracts.
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of the Institute’s scientists. As all external grants are “taxed” for “overheads”, the research groups at the Institute, beyond contributing the scientific and human excellence upon which the Gulbenkian Institute’s reputation is built, also provide a significant fraction of the costs involved in running the IGC, and should be acknowledged for that. In short, the current financial situation at the Institute should ensure the Foundation that mercenaries are kept out.
about “self-correction”? Clearly, as seriously discussed by others over the last years, many of these problems arise by the very nature of processes and mechanisms currently used to finance scientific research, particularly from public sources. Hence, the institutional responsibilities of endorsing alternative values, and the critical role of Foundations in contributing to (re)establishing such values, a role that may only find equivalence in the Renaissance princes, who prepared for the Enlightenment and started the long road to a reason-based society, as only science may bring us.
A BIT OF SCIENCE Science is done by individuals, and while a most collective enterprise, it does find much of its interest in the diversity of scientists. Contrary to popular belief, there are as many ways of doing science as there are scientists. In science, there is no authority other than reason and knowledge, making it possible and healthy that the youngest of scientists disagrees with the older and wiser. No truth is final, and even for those that have been “established”, there will always exist better, broader or more profound, simpler and more beautiful versions of that truth. Experience, on the other hand, is usually necessary for wisdom, for it reveals regularities and builds upon “established” truths. Yet, if we want science to progress, “established” truths must be progressively revised, in that inexorable progress towards a better and more complete understanding of the world. This is why young, creative scientists must absolutely be given that possibility, not only of questioning the current truths, but also of contributing new, improved versions of our truths, let alone find new ones all together. The youngest carry the lightest weight of the “establishment” and are thus in the best position to question and revise, but this privileged position will rapidly disappear with experience and age, with the full acceptance of an order of things who are older know it, and have contributed to establish. In other words, there is a critical time in life when younger scientists may contribute novelty, also because they have fewer concerns with science policies and administration, with grant management and group productivity. Hence, it is the primary obligation of institutions and of those in charge of decisions to see to that the youngest do have these possibilities. This is perhaps the most important and difficult duty, but a most pleasant responsibility, for those who are at the helm of a scientific institution: in science at least, empower the youngest! However high the risk may be, however “wasteful” this policy is, it is necessary that some of the youngest succeed, at the risk of being left only with “established” scientists to continue to produce more “established” science. There are perhaps enough “established” scientists to carry on with what clearly has to be done. In contrast, novelty is unpredictable, it may take a specific context and a unique person to bring it about, but it may well open up new solutions to old problems, often in dramatic manners. It follows that the responsibility of institutions and decision-makers in this respect is correspondingly greater. Together with the wisdom that allows for the right balance between “established” and “newcomer” scientists, this is what is required for a productive science institution.
Hence, the institutional responsibilities of endorsing alternative values, and the critical role of Foundations in contributing to (re)establishing such values, a role that may only find equivalence in the Renaissance princes, who prepared for the Enlightenment and started the long road to a reason-based society, as only science may bring us.
ANTÓNIO COUTINHO Director March 2011
Young, creative scientists must absolutely be given that possibility, not only of questioning the current truths, but also of contributing new, improved versions of our truths, let alone find new ones all together.
Speaking about the younger generations of scientists, we must ask what is the “state of science” that we, older generations, leave to them. Many scientists of my age often share the feeling that, irrespective of our generation’s scientific achievements, we did not manage to preserve all aspects of the “right” way of doing science and of being in science. This amounts to expressing our disaffection with some aspects of today’s science practices (e.g., decisions on careers being essentially left to journal editors, who pursue primary objectives of a totally distinct nature; the rule that the best competitors will always be those who have more money and larger groups), but also to recognise that the younger generations inherit a world of science that is not necessarily ideal. In many respects, we hope for the younger generations to succeed where we failed, and correct all we left deteriorating. In other forms of creative human activities, such as the arts or literature, the discontentment with current ways of doing things have recurrently given rise to “movements”, of variable impact and relevance, but always starting from a frontal rejection of the ”establishment”. Strangely, perhaps, these do not arise in science, at least not with the significance that we are used to seeing in other fields. Are we to conclude that scientists are more conservative than artists and writers? Or that the processes that are required in science for individuals to gain recognition are always filtered through the “establishment”? Or that the very nature of science (including the requirement that others reproduce one’s experiments and results) brings
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THE IGC AT A GLANCE The Instituto Gulbenkian de Ciência is an international biomedical research and graduate training institute, dedicated to promoting multidisciplinary science of excellence and a new generation of scientific leaders. The IGC operates as a host institution that provides an entrance hall into Portugal for national and international researchers and clinicians, with a view to setting up and developing research programmes of excellence and strengthening the scientific community, in the country and abroad. The IGC mssions are thus: • To identify, educate and incubate new research leaders, providing stateof-the-art facilities and full financial and intellectual autonomy to pursue research projects; • To export new leaders in biomedical research to research centres and academia in Portugal and internationally; • To provide international graduate teaching and structured training programmes; • To promote a science-based culture and the values of science in society, as well as the active participation of society in scientific research, through engagement with different communities and stakeholders. The IGC was set up by the Calouste Gulbenkian Foundation. The institute is part of the Oeiras Campus, home to several other basic and applied research centres in biology, biotechnology and chemistry, including the ITQB Associated Laboratory, made up of the IGC, the Instituto de Tecnologia Química e Biológica (ITQB) and the Instituto de Biologia Experimental e Tecnológica (IBET). RESEARCH Research at the IGC is organism centred, hypothesis driven, transverse and multidisciplinary in approach. The focus is on the genetic bases of development and evolution of complex systems, spanning the following areas: • Genetics of complex diseases: malaria, diabetes Type I, lupus, • Host pathogens interactions, including malaria • Developmental biology in animals and plants • Cell biology, cell cycle and DNA repair • Behavioural neurobiology • Evolutionary biology • Inflammation, immunity and auto-immune diseases • Theoretical biology • Bioinformatics IGC PEOPLE In 2010: 260 researchers 4 PhD Programmes 47 Research Groups • 2 new research groups • 3 departing research groups 86 Post-docs 83 PhD students 44 Graduate Technical Staff
30 Nationalities working at the IGC 7 1 2 1 10 1 1 1 1 1 6 1 9 11 3
Germany Angola Argentina Australia Brazil Bulgaria Colombia Cuba Denmark Slovaquia Spain Estonia USA France Greece
3 2 7 1 5 3 1 1 1 4 1 281 1 1 1
Netherlands India England Israel Italy Japan Lebanon Lituania Luxemburg Mexico Poland Portugal Romania Serbia Sweden
The town of Oeiras, where the institute is located, is just 20km from Lisbon, on the coast. The IGC is within walking distance from the beach, and there is easy public transport access to Lisbon. The IGC’s parent organisation, the Calouste Gulbenkian Foundation in Lisbon has both a fine arts and a contemporary arts centre, as well as a world class concert season, all of which IGC members have access to.
COMPETITIVE AWARDS SECURED BY IGC RESEARCHERS: 20 Awards and Honours, including: • 1 The Scientist - Faculty of 1000 Best Places for Post-docs Award • 1 Pfizer Award in Basic Research 2010 • 1 Pfizer Award in Clinical Research 2010 • 1 Seeds of Science - Health Sciences 2010 Award • 6 Editorial Board / Scientific Editor nominations • 1 Council Member nomination 62 new research grants, including: • 1 Bill & Melinda Gates Foundation Grand Challenges Exploration • 1 European Research Council (ERC) Advanced Investigator Grant • 3 ERC Starting Grants • 2 Human Frontiers Science Programme Grant (HFSP) • 1 Association for International Cancer Research Grant • 1 FP7 Marie Curie International Reintegration Grant • 46 Fundação para a Ciência e a Tecnologia (Portugal) Research Grants
27 1st Year Doctoral Students
NEW COMPETITIVE GRANTS AWARDED TO THE IGC IN 2010 PER RESEARCH FUNDING BODY
26 Administrative staff 30 Nationalities
FUNDAÇÃO PARA A CIÊNCIA E TECNOLOGIA
46
350 Alumni (since 1993)
EUROPEAN COMMISSION
7 HFSP
SCIENTIFIC COMMUNICATION In the last 5 years: 480 Scientific Publications (Source: Web of Science) In 2010: 132 peer-reviewed publications 6 book chapters 6 PhD Theses 17 MSc Theses
2 EMBO + FCT + FCG
1 BILL & MELINDA GATES FOUNDATION
1
286 International presentations by IGC researchers 186 Seminars at IGC • 128 External speakers 8 Meetings at IGC
EMBO
1 ASSOCIAÇÃO VIVER A CIÊNCIA + CRIOESTAMINAL
1 CÂMARA MUNICIPAL DE OEIRAS
1 ASSOCIAÇÃO PARA O DESENVOLVIMENTO FCUPN
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THE IGC AT A GLANCE
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RESEARCH GROUPS
PROTEIN-NUCLEIC ACIDS INTERACTIONS Head: Alekos Athanasiadis PhD in Structural Biology University of Crete, Greece
Sequence is not fate. Proteins demonstrate a fundamental ability not only to recognise and bind to specific pieces of nucleic acids code but also to alter its information content by catalysing reactions that rearrange its sequence or specifically change one nucleotide for another. We study the molecular details and the fundamental concepts that drive these intimate interactions between the major biological macromolecules. RECOGNITION OF FOREIGN NUCLEIC ACIDS IN INNATE IMMUNITY We are aiming to characterise the protein/nucleic acids interactions involved in this interferon response pathway by means of biochemistry and structural biology. We concluded and published the crystal structure of the ADAR1 Zalpha domains bound to a DNA duplex forming a Z-Z junction at 2.6 Angstroms resolution. The DNA sequence CGCGCGACGCGCGCG comprises of two Z-DNA forming segments interrupted by a single base pair that brings the Z-DNA segments out of phase. The structure demonstrates that Z-domains can bind left handed helices not only in isolation but also in the context of a natural DNA sequence that contains imperfections of the prototypical Pu/Py repeat. It also shows that the junction bases become disordered and exposed to chemical or enzymatic modification, an observation of great significance for the accumulation of DNA damage at genomic sites rich in CpG repeats. The work was published this year in PNAS. A TO I RNA EDITING AND MOLECULAR EVOLUTION We are developing a computational platform that allows agent based evolution of single - few gene organisms in the presence of RNA editing allowing the exploration of wide range evolutionary and editing parameters. Funded by IGC.
GROUP MEMBERS Matteo de Rosa (Post doc) Theokliti Tsigkri (Research Technician) Ana Rita Tome (Research Technician) COLLABORATIONS Maria Arménia Carrondo (ITQB) Alexander Rich (Massachusetts Institute of Technology) Stefan Maas (Lehigh University/NIH) FUNDING Marie Curie International Reintegration Grant, European Commission Instituto Gulbenkian de Ciência
Recognition of DNA CpG repeats by the Z-domain family, a DNA binding domain present in interferon response proteins involved in the recognition of foreign nucleic acids. Zalpha bound to a Z-Z DNA Junction.
A cavity formed at the junction between two CGCGCG segments can become site for intercalating agents. Here a HEPES molecule intercalates in the DNA helix.
COMPUTATIONAL MODELS OF GENE EVOLUTION IN THE PRESENCE OR ABSENCE OF RNA EDITING. Low levels of RNA editing are shown to accelerate evolution rates relative to the no editing controls (dashed yellow line). The plot shows the maximum fitness levels after 5000 generations of simulation under variable parameterisation.
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PLANT STRESS SIGNALING
MEIOSIS AND DEVELOPEMENT
Head: Elena Baena González
Head: Vítor Barbosa
PhD in Plant Physiology and Molecular Biology University of Turku, Finland
PhD in Genetics University of Cambridge, UK
Plant growth is intimately connected to the environment, resulting in striking developmental plasticity that allows the plant to modify its growth pattern according to the changing conditions. Environmental stress (e.g. drought, shading, cold, salinity, pollutants) can have a great impact on the decision to grow, to initiate organogenesis as well as on the characteristics of the newly formed organs. Under stressful conditions energy production through photosynthesis and/or respiration is reduced, causing an energy deficit in the cell and subsequent growth arrest. Work in our laboratory focuses on the SnRK1 signaling cascade that is central to the sensing of stress-triggered energy deprivation and to the subsequent orchestration of gene expression changes and enzyme regulation necessary for recovery and adaptation. Our goal is the dissection of this key pathway and the deeper characterisation of the cellular processes under SnRK1 control as a first step to understand how stress cues are translated into growth and developmental decisions that contribute to stress tolerance and adaptation. We use Arabidopsis thaliana as a model and a combination of cell-based assays, functional genomics, biochemistry, mutant screens and genetics to investigate how SnRK1 is regulated and to identify other upstream and downstream components of this signaling cascade.
GROUP MEMBERS Ana Augusto Confraria (Post-doc) Rafal Butowt (Post-doc; left July 2010) Américo Rodrigues (Visiting scientist; Post-doc) Cláudia Martinho (PhD student) Carlos Elias (Research Technician) Leonor Duarte (Research Technician; left Sept. 2010) COLLABORATIONS Jen Sheen, Mark Borowsky, Brad Chapman (Massachusetts General Hospital, Boston, MA, USA) Ignacio Rubio Somoza, Detlef Weigel (Max Planck Institute for Developmental Biology, Tuebingen) Pedro L. Rodriguez Egea (Universidad Politécnica de Valencia, C.S.I.C.) FUNDING Marie Curie International Reintegration Grant, European Commission European Molecular Biology Organisation (EMBO) Fundação para a Ciência e a Tecnologia (FCT), Portugal Conselho de Reitores das Universidades Portuguesas (CRUP), Portugal
GROUP MEMBERS Raquel Santos (PhD Student) Patrícia Silva (MSc Student) Triin Laos (MSc Student) Ana Bernardo (MSc Student) Carla Morais (Trainee) COLLABORATIONS Caryn Navarro (Boston University School of Medicine, USA) FUNDING Marie Curie International Reintegration Grant, European Comission Fundação para a Ciência e a Tecnologia (FCT), Portugal
dPds5 FOCI DEPEND ON MAINTENANCE OF THE OOCYTE FATE. Expression of dPds5 tagged with GFP under the control of a germ cell-specific promotor nos in stage 7 egg chambers. The wild type chamber shows diffuse localisation of dPds5:GFP on chromatin of 15 polyploid nurse cell nuclei and a unique punctate distribution in the oocyte (arrowhead). In egalitarian mutants where oocyte fate is lost at this stage egg chambers show 16 nuclei with nurse cell-like distribution of dPds5:GFP.
We found further evidence that dPds5 is required in the oocyte to organise meiotic chromatin in higher-order structures required for cell-specific transcription. This includes imunolocalisation of Poly-A-binding protein and active Polymerase II in the oocyte of the wild-type oocyte in contrast to dPds5 mutant oocytes.
ENERGY SIGNALING IN THE STRESS RESPONSE In order to expand our knowledge on the diversity of processes regulated by SnRK1s as well as on the molecular regulatory mechanisms underlying SnRK1 action, this project aims to determine the significance of nuclear localisation, post-translational modification and protein stability for SnRK1 action, and initiate genetic and yeast two-hybrid screens (Y2H) for the identification of novel components of the SnRK1 signaling cascade. We have gained new insights into the nature of SnRK1 post-translational modification and developed tools for functional studies of this modification in the protoplast system and in plants. We have also carried out preliminary identification of putative SnRK1 regulators through functional genomics screen in the protoplast system and of novel SnRK1 interacting partners.
We found a unique localisation of dPds5:TAGs in foci within the oocyte nucleus. These foci co-localised neither with the nuclear envelope nor with the meiotic chromatin condensed into a karyosome. Consistent with a hypothetical role of dPds5 in transcription regulation, we found that these foci co-localise with a promiscuous insulator body component CP190. Such colocalisation follows the same dynamics along oogenesis. Moreover, CP190 localisation is affected in dPds5 mutant oocytes.
dPds5 IS REQUIRED FOR TRANSCRIPTION IN THE OOCYTE. Localisation of the phosphorylated serine 5 residue of the RNA polymerase II carboxi-terminal (pSer5CTD, red) with respect to DNA (blue) in stage 6/7 egg chambers. Absence of nls:GFP (green) marks clones of germ cells homozygous for a dPds5 null mutation. Mutant oocyte shows a decreased amount of pSer5CTD in contrast to the wild-type oocyte (arrowheads) or to other dPds5 mutant germ line cells in the same chamber.
MEIOSIS AND DEVELPMENT We are carrying out screens for piRNA mutants in our maternal mutant collection using stainings against the microtubule-base transport protein BicD as readout. The project also entails screens for deficiencies that genetically interact by synthetic female sterility with previously discovered piRNA mutants montecristo and sancho panza.
Our main goal is to understand how the SnRK1 system integrates metabolic and environmental cues into growth and developmental patterns. To this end a deeper knowledge is required on how SnRK1s are regulated and therefore we are currently undertaking several complementary strategies to dissect and characterise in depth the SnRK1 signaling cascade.
IGC ANNUAL REPORT ‘10
1. Characterise a new DDR to structural defects in the chromatin. We have discovered that an insulator body component is under surveillance specifically in the oocyte; 2. Investigate oocyte-specific transcription. We are focused on the characterisation of the gene pool specifically expressed in the oocyte as well as the set of protein interactions occurring in these oocyte insulator bodies; 3. Study DDR control along oogenesis. Specifically, we want to know how DDR is activated by germline-specific mobilisation of selfish elements at different time points of oogenesis. STUDIES OF CHROMATID COHESION DURING MEIOSIS IN DROSOPHILA MELANOGASTER REVEAL A NOVEL DNA DAMAGE CHECKPOINT PATHWAY ESSENTIAL FOR OOCYTE POLARITY The aims of this project are to characterise the phenotype of dPds5 mutant germ cells in terms of their transcriptional activity using chromatin markers; to describe the localisation of functional tagged dPds5 transgenes in the oocyte with respect to other germ cells and soma; to test the tags: GFP, Venus, Myc and FLAG. Furthermore, we aim to identify earlier components of the checkpoint that monitor the meiotic function of dPds5, and define downstream effectors of the new DDR pathway identified through studies on dPds5 mutants.
THE ROLE OF miRNAs IN PLANT ENERGY SIGNALING The overall aim of this project is to investigate the hypothesis that miRNAs execute part of the SnRK1-mediated stress response in plants. Specifically, we aim to generate and carry out high throughput sequencing of small RNA libraries associated with energy deprivation and SnRK1 activation; investigate the SnRK1-associated stress transcriptome in the absence of functional small RNA pathways; functionally characterize identified miRNAs as well as elucidate and validate their targets. Towards these aims a second set of small RNA libraries associated with energy deprivation have been generated and resolved using high throughput sequencing (HTS). Preliminary analyses of HTS data have uncovered differentially expressed miRNAs in control vs. energy deprivation conditions. Gain- and loss-of-function assays of these miRNAs are currently being developed to address their function and their connection to the SnRK1 signaling pathway.
RESEARCH GROUPS
We study the links between meiosis and oocyte polarity. In Drosophila females, the integrity of the meiotic chromatin is monitored by a checkpoint whose activation affects gamete polarity and viability. Persistent double strand breaks from meiotic recombination activate a conserved DNA damage response (DDR), which causes defects in the dorsal-ventral (DV) polarity of the eggshell. With a panel of germline mutations that cause eggshell "ventralisation" we want to:
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By 2010, 30% of the mutants have been rescreened. One whole candidate complementation group (trinidad) and a singleton line (A43-47) have been identified with abnormal BicD staining typical of piRNA mutants. Two 3rd chromosome deficiencies have been identified.
IGC ANNUAL REPORT ‘10
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TRINIDAD MUTANTS FORM BicD CLUMPS. Stage 7 egg chambers showing the distribution of the microtubule dynein binding cargo linker component Bicaudal D (BicD, green) with respect to DNA (blue). In contrast to wild type, BicD forms cytoplasmic aggregates in trinidad mutant nurse cells, typical of transposon amplification in piRNA mutants.
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EPIGENETICS AND SOMA
VARIATION: DEVELOPMENT AND SELECTION
Head: Vasco Barreto
Head: Patrícia Beldade
PhD in Immunology Université Paris VI, France
PhD in Evolution and Development Leiden University, The Netherlands external website: http://www.beldade.nl
Immunoglobulin genes are remarkable in two ways. Unlike almost any other gene, they undergo a process of somatic editing, rendering each allele from each maturing B cell unique, and producing antibodies of improved affinity over the course of an immune reaction. Unlike most other autosomal genes, immunoglobulin alleles are monoallelically expressed. We study these two phenomena as part of the B cell biology, but our ultimate goal is to address the epigenetic nature of random monoallelic expression and the impact of DNA editing mechanisms in a broader context. We are currently interested in understanding the role of the C-terminus of this molecule in class switch recombination (CSR). We are also producing hyper-active AID mutants and detailing the expression and role of this enzyme in the germline, where it has been found. Finally, since AID is a mutator molecule, we are developing mouse strains to address the impact of the ectopic expression of AID in a cancer model and we started an experiment to evaluate how AID and another DNA editing enzyme affect the signature sequence of genomic translocations. Random monoallelic expression is the ultimate example of epigenetics, since within each cell the two virtually identical molecules will behave in opposite ways - expression or silencing. Here our approach is not centered on a molecule, but on a strategy: we are conducting a clonal analysis, both in vitro and in vivo, to address the epigenetic constraints of this process.
GROUP MEMBERS Catarina Cortesão (Post-doc) Thiago Guzzela (PhD student) Inês Trancoso (PhD student) Clara Pereira (PhD student) Filipa Marta (Research Technician) Daniel Espadinha (Research Technician) COLLABORATIONS Paulo Vieira (Institut Pasteur, France) Maria Vieria da Silva (Instituto Português de Oncologia, Portugal) Paula Gameiro (Instituto Português de Oncologia, Portugal) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal Marie Curie International Reintegration Grant, European Commission Terry Fox Award - Liga Portuguesa Contra o Cancro (LPCC), Portugal Associação Portuguesa Contra a Leucemia (APCL), Portugal
STUDIES ON AID II Our aims are to evaluate the impact of ectopic expression of AID during aberrant processes leading to tumor formation and to generate in vivo data for the expression of AID in the context of chronic inflammation. We have produced a number of strains that are essential for this project and we have started preliminary imaging experiments.
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COLLABORATIONS Anthony Long (University of California at Irvine, USA) Paul Brakefield (Leiden University, The Netherlands) Vassilis Douris (Leiden University, The Netherlands) Suzanne Saenko (Leiden University, The Netherlands) Tom van Dooren (École Normale Supérieure de Paris, France) Christian Peeters (Université Pierre-et-Marie Curie, Paris, France) André Freitas (Universidade Estadual de Campinas, Brazil) Filipa Abreu (Instituto Gulbenkian de Ciência, Portugal) Sara Monteiro (Instituto Superior de Agronomia, Portugal) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal
1. The genetics of multiple pigmentation variants; 2. The genomic sequence around eleven genes expressed in developing wings (involving annotation and comparative analysis); 3. A locus responsible for variation in an evolutionary novelty (butterfly eyespots) and for a shared developmental process (insect embryogenesis); 4. The expression of a number of key eyespot genes in multiple butterfly species.
THE IN VIVO ACTIVATION OF AID IS DETECTED BY THE EXPRESSION OF THE YELLOW FLUORESCENT PROTEIN (YFP) IN MICE (F1) THAT HAVE THE RECOMBINASE CRE IN THE AICDA LOCUS (THE GENE THAT ENCODES AID) AND A YFP REPORTER THAT IS ONLY ACTIVATED AFTER EXPRESSION OF CRE (ROSA 26YFP). A - Splenic B cells were stimulated in vivo with stimuli known to activate AID (LPS+IL4) or not (anti-RP105). B - qRT-PCR data for the expression of AID (the Cre knock-in disrupts Aicda, which explain the absence of the AID transcript). C - Flow cytometrry data of blood cells stained for a B cell marker (CD19). A low percentage of YFP + is only detected in the B cell pool of the F1 animals.
DIRECTED EVOLUTION OF AID Our objective is to isolate mutants of AID with enhanced cytidine deaminase activity in vivo, so that we can study the basic biology of this molecule and produce animal models of cancer. We have performed a complete cycle of selection and we are ready to enter the part of the project in which we will reiterate this step a number of times. AID IN CHRONIC LYMPHOCYTIC LEUKEMIA We plan to determine the physiologic relevance of AID isoforms in CLL. Ultimately, our goal is to develop a mouse model of CLL in which the expression of AID can be followed. Our preliminary results suggest that the isoforms are catalytically inactive, except AID-ivs3. To our knowledge, it is the first time that the isoforms are tested by this assay. We are in the process of confirming these preliminary data.
GROUP MEMBERS Roberto A. Keller (Post-doc) Inês Conceição (Post-doc) Ana Rita Mateus (PhD student) Leila Shirai (PhD student) Maria A. Jerónimo (Laboratory Technician; MSc Student) Ana Marcelino (MSc Student; left November 2010)
EVOLUTIONARY DIVERSIFICATION: GENETIC BASIS AND ADAPTIVE SIGNIFICANCE OF VARIATION IN BUTTERFLY WING PATTERNS This project analyses different types of phenotypic variation (quantitative genetic variation and alleles of large effect) at the ecological (fitness consequences of variant morphologies) and genetic (gene mapping and gene expression analysis) levels. We characterised:
ON THE EPIGENETIC NATURE OF IMMUNOGLOBULIN GENE MONOALLELIC EXPRESSION Our preliminary data support the notion that random autosomal monoallelic expression has unique features, not shared with X- chromosome inactivation. Our immediate goal is to test whether there is an epigenetic imprint that determines which Ig allele recombines first. We have complemented the in vitro data of last year with in vivo experiments. Essentially, we optimised a protocol for single-hematopoietic stem cell reconstitution and we have analysed the hematopoietic system in this reconstituted mice for the expression of the IgH alleles. STUDIES ON AID I Our objective was to clarify the status of the residue S38 in the phylogeny of AID. The next goal is to move from the analysis of AID orthologues to the isolation of DNA mutators from invertebrate species. We have concluded the functional analysis of the shark AID.
My research in evolutionary developmental biology is focused on the genetic and developmental basis of phenotypic variation and adaptation. Heritable phenotypic variation is the raw material of evolution by natural selection, and a universal property of biological systems - including traits of medical and economic importance. Understanding the mechanisms that generate this variation is a key challenge in biological research. What are the gene types (e.g. transcription factors versus enzymes), specific genes, and gene regions (e.g. regulatory versus coding sequence) that contribute to evolutionarily relevant variation? How do they affect developmental programmes and translate into variant adult phenotypes and finally into phenotypic diversification? How does the external environment regulate organismal development to account for adaptive phenotypic plasticity? To address these and other questions the lab is currently using two systems for the dissection of variation in complex, diversified and ecologically-relevant phenotypes: wing colour patterns in butterflies, and caste morphology in ants.
THE CONTRIBUTION OF NOVEL GENES TO THE FORMATION OF EVOLUTIONARY NOVELTIES This project tests the involvement of candidate, lineage-specific genes in the development of lineage-specific features by characterising complementary aspects: gene sequence (in silico analysis), gene expression (spatial patterns and quantitative levels), and gene function (manipulating gene expression) in developing butterfly wings. We started the detailed in silico analysis of ~200 candidate novel genes, including a search for: 1. Repetitive and coding regions; 2. Putative functional domains; 3. Orthologous genes in public depositories. This analysis will generate a short-list of candidate genes for further study.
GATING STRATEGY FOR THE ISOLATION OF THE HEMATOPOIETIC STEM CELLS (HSCS) USED IN OUR IN VIVO CLONAL ASSAYS. Different antibodies against surface markers are used to sequentially restrict the population of isolated from total bone marrow cells, as shown. In the top right plot, cells incorporate the dye Hoechst 33342, but HSCs tend to efflux it. This difference is explored in the final step of isolation.
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COPING WITH CHANGING ENVIRONMENTS: GENETIC AND PHYSIOLOGICAL MECHANISMS OF ADAPTIVE PLASTICITY This study investigates the proximate mechanisms (genetic and physiological) behind developmental plasticity in butterfly wing patterns, and explores their potential role in enabling species to cope with changing environments. We have characterised the effects of ecdysteroid manipulations in pupae on multiple aspects of development (including developmental time and the dynamics of pigment synthesis) and on adult phenotypes (including wing patterns and body-part allocations). We also produced a broad-scope review about “adaptive developmental plasticity”.
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MUTANTS OF BICYCLUS ANYNANA BUTTERFLIES WITH ALTERED EYESPOT MORPHOLOGY (a) AND DISTURBED EMBRYOGENESIS (b). The corresponding locus encodes a putative novel regulator of Wingless signaling and is located in a genomic region representing a “hotspot” for wing pattern diversification. Adapted from Saenko et al. BMC Biol 2010.
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CELL CYCLE REGULATION Head: Mónica Bettencourt Dias
EVOLUTION OF CASTE POLYPHENISM IN SOCIAL INSECTS: PATTERNS OF MORPHOLOGICAL DIVERSIFICATION IN ANTS This project studies how plastic developmental systems are regulated, and how they evolve and diversify. Specifically, we want to:
PhD in Molecular Cell Biology University College London, UK external website: http://sites.igc.gulbenkian.pt/ccr/
1. Establish a link between caste-specific morphologies and behaviours, in relation colony ecology; 2. Characterise the environmental regulation of caste development. We produced a detailed characterisation of caste-specific morphologies (skeletal and muscular systems) for multiple species of ants, and correlated these with alternative behaviours (at the level of caste-specific roles within a colony, and of reproductive strategies of whole colonies). This will be the basis for analysing the development of the alternative phenotypes. MORPHOLOGICAL DIVERSIFICATION THROUGH THE EVOLUTION OF DEVELOPMENTAL NETWORKS This project will attempt to establish a link between diversification of different aspects of morphology and modifications of different stages of pattern formation and their underlying genetic networks. This project started in 2010 and is still in the phase of familiarisation with biological system and relevant literature and defining experimental design.
DEVELOPMENTAL PLASTICITY AND UNDERLYING MOLECULAR MECHANISMS IN TWO TARGET INSECT SYSTEMS. Alternative butterfly wing pattern phenotypes obtained by rearing larvae at different temperatures (a) and corresponding changes in hormone dynamics in developing pupae (b). Recent studies linked the development of morphologically different social insect castes, example of fire ant large winged queen and small wingless workers (c) (photo by Alex Wild), to levels of methylation during development, example of knock down of methylation enzymes in honeybee larvae (d). Adapted from Beldade et al. Mol Ecol invited review (in press).
Our research focuses on cell cycle progression and the cytoskeleton in normal development and disease. We are particularly interested in the role played by microtubule organising structures, such as the centrosome, cilia and flagella. The centrosome is the major microtubule organiser in animal cells, and is very often abnormal in cancer. Cilia and flagella are cellular projections which are indispensable in a variety of cellular and developmental processes including cell motility, propagation of morphogenic signals and sensory reception. Despite their importance, we know very little about centrosome and cilia biogenesis or how they may go awry in human disease. Our laboratory combines studies in model organisms with studies in human cells, bioinformatics and mathematical modeling to have an integrated view of this process. The fruit fly is an excellent organism to address those questions, since it combines possibilities of screening multiple genes with the ability to perform in-depth regulation studies in the whole organism. As the regulatory mechanisms of the cell cycle and cytoskeleton have been highly conserved throughout evolution, we can extrapolate our findings to humans to test their relevance for human disease. An understanding of the pathways involved in cell cycle and cytoskeleton can generate diagnostic and prognostic markers and hopefully provide novel therapeutic targets in human disease. REGULATION OF CENTRIOLE BIOGENESIS AND FUNCTION: AN INTEGRATIVE APPROACH In collaboration with the IGC Computational Genomics laboratory and over 25 experts scattered throughout the world, we are creating phylogenetic profiles of molecular players in centriole assembly and correlating them with the evolution of the morphology of centrioles using mostly published electron micrographs. We have started to assemble a database using controlled vocabulary and linking protein repertoires with morphological diversity.
GROUP MEMBERS Ana Rodrigues Martins (Post-doc; left May 2010) Daniela Brito (Post-doc) Mariana Faria (Post-doc) Susana Gouveia (Post-doc) Zita Carvalho Santos (PhD student) Filipe Leal (PhD student) Inês Bento (PhD Student) Inês Ferreira (PhD Student) Pedro Machado (Research Technician) Tiago Amado (ResearchTechnician) COLLABORATIONS Eric Karsenti (EMBL, Heidelberg, Germany) Juliette Azimzadeh (University of Cambridge, UK) Keith Gull(Institut Curie, France) Michel Bornens (University of Oxford, UK) David Glover (University of California at San Francisco, USA) José Pereira-Leal (Instituto Gulbenkian de Ciência, Portugal) Miguel Godinho (Instituto Gulbenkian de Ciência, Portugal) Brian Tsou (Sloan Kettering, USA) David Pellman (Harvard Medical School, USA) Max Loda (Harvard Medical School, USA) Paula Chaves (Instituto Português de Oncologia, Portugal) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal European Molecular Biology Organisation (EMBO)
REGULATION OF THE TUMORIGENESIS-RELATED KINASE SAK/PLK4 We aim to understand the regulation of PLK4 activity in time and space. Using both Drosophila and human tissue culture we are now addressing the regulation of SCF/Slimb mediated SAK/PLK4 destruction. We are doing so by investigating novel PLK4 interactors and by investigating how the PLK4Slimb interaction is regulated by phosphorylation. This will allow us to understand how only one daughter centriole is formed close to each mother centriole. We have developed tools and assays in Drosophila and Xenopus extracts (antibodies and live imaging) that will allow us to follow the degradation of PLK4 in cells and extracts. REGULATION OF CILIA BIOGENESIS IN DEVELOPMENT AND HUMAN DISEASE The first described intermediate in centriole assembly showing nine-fold symmetry is a structure called cartwheel. Bld10/CEP135 and SAS-6 are two components of the cartwheel. We have shown SAS-6 mutations lead to failure to form centrioles, with those that form being short and showing abnormal symmetry. We have recently found that Bld10 is likely to play a role in the assembly of the transition zone of Drosophila sperm (A1). Mutants in Bld10 and in SAS-6 show axonemes that lack the central microtubule pair, are immotile, and males are sterile. Nine-fold symmetrical structures can be clearly seen in the TZ of certain species, such as Chlamydomonas and Tetrahymena. We hypothesise that similarly to the function of the cartwheel in procentriole assembly, the TZ may reinforce the nine-fold symmetry of the axoneme, and start the de novo formation of structures, such as the central pair of microtubules. We are exploring these parallels, in particular by studying the function, regulation and interaction partners of SAS6 and BLD10 in centriole and axoneme formation. Drosophila testes are particularly useful to tackle this question as centrioles/basal bodies are particularly long and easy to image. We have found a new percursor structure of the central microtubule pair in spermatocyte primary cilia. These structures are missing in Bld10 mutants.
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CENTROSOME - CENTROSOME AND CILIA STRUCTURE. THE CENTRIOLE/ BASAL BODY IS A STRUCTURAL CONSTITUENT OF THE CENTROSOME AND OF CILIA AND/OR FLAGELLA. A - The canonical centriole has nine microtubule triplets. Each centrosome is composed by a mother and daugther centriole, in an orthogonal configuration, surrounded by a matrix of proteins, the pericentriolar material (PCM). The older centriole shows subdistal appendages, where Mts are docked and distal appendages, which are important for docking to the membrane. B - In many cells the centriole, then called basal body, migrates and tethers to the membrane via its appendages and seeds the growth of cilia and flagella. The skeleton of cilia and flagella, called the axoneme, results from a continuation of the basal body structure and might be composed of nine doublets with no dynein arms nor central pair, as it is in the case of most immotile cilia; or nine MT doublets with dynein arms and a central MT pair, as it is for most motile cilia.
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QUANTITATIVE ORGANISM BIOLOGY Head: Jorge Carneiro
REGULATION OF CENTRIOLE NUMBER IN DEVELOPMENT We are now describing the regulation of centrosome proteins in the female germline in order to get insights into the factors that regulate centriole disappearance and that prevent de novo formation. We are completing the description of the cascade of events during oogenesis, which correlates with centriole loss.
PhD in Biomedicine Universidade do Porto, Portugal external website: http://qobweb.igc.gulbenkian.pt
SPERMATOGENESIS - DROSOPHILA SPERMATOGENESIS AND SPERMATID ELONGATION. A - During spermatogenesis, each stem cell division produces a gonial cell that undergoes four rounds of mitotic divisions to produce a cyst of 16 primary spermatocytes. These are connected through 15 ring canals as a result of incomplete cytokinesis. Each of these cells has four centrioles (red bars) and undertakes a prolonged G2 phase, where both the cells and their centrioles grow substantially. The Transition zone is formed at this stage and it is very long. B - Centrioles within the centrosome remain close together in a V-shape. C - During this phase, all centrioles/basal bodies within each cell migrate to the membrane to form a small cilium. Afterwards they migrate again to a position closer to the nucleus, in preparation for meiosis. Meiotic divisions produce a cyst of 64 interconnected spermatids, each with one centriole/basal body. Early spermatids have a single nucleus (white sphere) and a mitochondrial derivative (Nebenkern, black sphere) of similar sizes. D - The basal body organises the flagellar axoneme of the sperm.
Cells of multicellular organisms cooperate to ensure body development and maintenance. They do this in a collective distributed manner, without any master or plan. The Quantitative Organism Biology group studies the multilevel mechanisms that give rise to whole organism properties, in search for general principles of biological organisation and, eventually, the design of artificial systems. One of our main research interest is the immune system, whose cells collectively ensure body housekeeping and homeostasis, prevent autoimmune diseases, and fight cancer and infections. We also investigate cell and tissue morphodynamic processes taking place during embryonic development to generate metazoan body shapes.
GROUP MEMBERS Danesh Tarapore (Post-doc) Tiago Macedo (PhD student) TIago Guzella (PhD student) Tom Weber (External PhD student) Pedro Silva (MSc student)
BIOINSTBOTS: FROM BIO-INSPIRED TO INSTITUTIONAL-INSPIRED COLLECTIVE ROBOTICS The aim of the project is to reach a synthesis of biological and institutional theory of collective behaviour, providing novel cooperation and coordination algorithms and methods for collective robotics based on a formal framework for collective systems. A synthetic theory of collective behaviour inspired on biological cells requires as an absolute pre-requisite detailed quantitative simulations of cell populations and tissue that can be rigorously formalised and validated by comparison with the natural system. During this first year of the project we have worked on formalising and implementing simulations of three biological system that will be used as case studies:
FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal. Conacyt - Consejo Nacional de Ciencia y Tecnología, Mexico.
COLLABORATIONS Pedro Lima (Institute for Theoretical Biology, Berlin, Germany) Alberto Darszon (Department of Mathematics. University of Leeds, UK) Carmen Molina-Paris (UNAM, Cuernavaca, Mexico) Grant Lythe (UNAM, Cuernavaca, Mexico) Michal Or-Guil (Instituto Superior Técnico, Portugal)
1. CD4 T cell differentiation and population dynamics, which serves as a good model for task allocation and distributed control; 2. Spatial pattern formation and dynamics in cell aggregates and tissues as an example of self-organisation; 3. Spermatozoa fertilisation, as a case of spatial exploration other than the collective foraging that has inspired swarm robotics. MORPHODYNAMIC MODELLING AND IMAGING OF SEA URCHIN SPERMATOZOA SWIMMING AND CHEMOTAXIS We aim to develop morphodynamic models of sperm cells and deploy these models for quantitative image analysis. In a nutshell, we propose to incorporate mechanistic information about flagellar regulation into the algorithms that coordinate our imaging system to analyse and determine sperm position, shape, trajectory, intracellular Ca2+ concentration and mutual interactions in space and time. We had developed a spermatozoan model that integrates, in the same framework, the molecular signalling networks controlling intracellular Ca2+, the flagellum morphodynamics, and the swimming behaviour in the presence or absence of spatial environmental cues. We had shown previously that this integrated model could qualitatively describe the trajectories of the chemotactic and non-chemotactic spermatozoa of Lytechinus pictus and Strongylocentrotus purpuratus, respectively. During the last year, we made substantial progress by making this integrated model fully quantitative, and we took the first steps towards quantitavely assessing the species-specific particularities of the sperm's sensorimotor system from two sea urchine species.
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MOLECULAR NEUROBIOLOGY
POPULATION AND CONSERVATION GENETICS
Head: Diogo Castro
Head: Lounès Chikhi
PhD in Cell and Molecular Biology Karolinska Institute, Stockholm, Sweden
PhD in Population Genetics University Pierre et Marie Curie, France external website: http://www.compbio.igc.gulbenkian.pt/pcg_home.html
THIS GROUP WAS ESTABLISHED AT THE IGC IN OCTOBER 2010
The assembly of a fully functional nervous system, with all its diversity and complexity, depends on the coordinated generation of both neurons and glia from differentiating multipotent neural stem cells in the developing embryo. The progression of this differentiation process is associated and controlled by changes in gene expression programmes that need to be very tightly regulated. For the moment we are mostly interested in understanding how such regulation takes place at the transcription level, by focusing our studies on the role played by various transcription factors in neurogenesis. We aim at characterising their transcriptional networks, as well as understanding the molecular mechanisms by which such programmes are regulated, and how they contribute to the acquisition of specific cellular phenotypes. For that we take advantage of recently developed genomic approaches that allow the characterisation of transcriptional programmes at a genome wide level (eg. ChIP-on-chip or ChIP-seq). We use such techniques, complemented with more classical methods to study gene expression, having the mouse embryo as a model system. Although the studies we conduct are within so called basic research, understanding how tissue specific patterns of gene expression are established during development will be of great importance, should stem cell technology be used in clinical applications.
The Population and Conservation Genetics Group (PCG) carries out research in the area of conservation and human population genetics. Genetic data can be used to reconstruct the recent demographic history of populations and species to identify key features of that history. For instance genetic data can be used to detect, quantify and date past population size changes such as collapses/bottlenecks and expansions. Admixture events whereby two or more populations "mix" to create new populations can also be analysed quantitatively. We are interested in understanding the statistical properties of genetic data in natural/wild or managed/domesticated populations (including breeds) to determine when and how genetic data can be used to make statements about the populations’ recent evolutionary history. We are also very interested in providing information that can be useful for conservation of rare and endangered species. For instance, besides genetic data we have also set up field work missions to estimate the numbers of remaining lemurs in the north and northwest of Madagascar. We also give importance to training and collaborations with local NGOs. Our work involves field and lab work together with data analysis, computer simulations, and the development of simulation tools.
GROUP MEMBERS Cécile Vanpé (Post-doc) Reeta Sharma (Post-doc) Vitor Sousa (PhD student; left January 2010) Jordi Salmona (PhD student) João Alves (PhD student) Bárbara Parreira (PhD student) Rita Rasteiro (PhD student) Sam Viana (Optimus Alive Research Fellow) Célia Rodrigues (Trainee) Isa Pais (Research Technician)
CHARACTERISATION OF A NEUROGENIC PROGRAMME AND ITS REGULATION BY THE VERTEBRATE PRONEURAL FACTOR MASH1 The aim of this project is to characterise the neurogenic differentiation programme regulated by the proneural factor Mash1 in a neural stem cell model. For that we have combined Mash1 ChIP-seq with expression profiling at different stages of differentiation. Gene expression clustering indicates that Mash1 directly binds to and regulates target genes with distinct kinetics profiles. We are currently investigating the mechanisms, both transcriptional and epigenetic, that are important for the establishment of such temporal patterning. This project was initiated at the National Institute for Medical Research (London, UK) and is being continued at the IGC.
DEMOGRAPHIC AND GENETIC RESPONSES TO HABITAT FRAGMENTATION AND HABITAT LOSS IN TWO LARGE FOREST MAMMALS The aims are to sample and genotype populations of two endangered large mammals from Borneo (Pygmy elephant and orang-utan). To reconstruct the demographic history of these species and understand the effect of habitat fragmentation on their genetic diversity. New genetic markers identified using next generation sequencing techniques (454 and Illumina). Multiplexes have been designed and tested ion blood and faecal mateiral. Very limited genetic diversity identified across microsatellites and SNPs identified this way. Altogether four papers published (two computer notes) - two free downloading software. There are still technical problems to solve to validate genotypes (degraded DNA and samples).
FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal Fondation pour la Recherche sur la Biodiversité, France
TRANSCRIPTION CONTROL OF VERTEBRATE NEUROGENESIS: FUNCTION OF THE TRANSCRIPTION FACTOR MYT1 The zinc-finger factor Myt1 has been previously shown to conteract Notch inhibition of differentiation in primary neurogenesis in Xenopus, by a mechanism yet to be determined. Its expression at the onset of neuronal differentiation suggests a conserved function in vertebrate neurogenesis. We aim to understand the mechanisms through which Myt1 may control the progression of the neurogenic programme, by characterising and studying the interaction between its transcriptional programme and those of the Notch effectors Hes1/5 and the proneural factor Mash1. A chromatin immunoprecipitation (ChIP) protocol for Myt1 in NS5 neural stem cells was developed, after screening a series of commercially availabe antibodies.
LEMUR CONSERVATION, PHYLOGEOGRAPHY AND GENETICS IN FRAGMENTED HABITATS FROM MADAGASCAR AND THE COMOROS ARCHIPELAGO Lemur conservation, phylogeography and genetics in fragmented habitats from Madagascar and the Comoros archipelago. This project aims to sample and genotype populations of endangered lemurs from the north and northwest of Madagascar, and estimate population sizes. To reconstruct their demographic history and understand the effect of habitat fragmentation on their genetic diversity. Non-invasive material has been collected and densities have been estimated for several Propithecus species. Papers have been published on both the genetic and density estimation work. Sampling of the Eulemur species has proven more difficult and sample sizes for wild animals are still limited.
GROUP MEMBERS Francisca Vasconcelos (PhD student) Pedro Rosmaninho (Trainee) COLLABORATIONS François Guillemot (MRC National Institute for Medical Research, London, UK) Stefan Momma (Johann Wolfgang Goethe University, Frankfurt, Germany) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal
Left - A neural enhancer of the Delta1 gene drives expression of a reporter in the developing nervous system of transgenic mouse embryos. Right - Its bound by the proneural factor Mash1 as revealed by ChIP-on-chip.
THE TRANSCRIPTIONAL NETWORK OF THE ZINC-FINGER FACTOR ZEB1 AND ITS FUNCTION IN NEURAL STEM/PROGENITOR CELLS Much work on the transcription factor Zeb1 has focused on its role as a regulator of a epithelial to mesenchymal trasition (EMT), both in embryonic development and tumor formation. In contrast, its function in neural stem/ progenitor cells, where it is strongly expressed, has not yet been addressed. We are investigating the function of Zeb1 in this cellular context, by a combination of mouse genetics and genomics. The analysis of a Zeb1 null mice model will be complemented with the characterisation of its transcriptional programme.
GENETIC EFFECTS OF HABITAT LOSS AND FRAGMENTATION: COMPARATIVE ANALYSIS OF SEVERAL LEMUR SPECIES IN TWO NEIGHBOURING REGIONS OF MADAGASCAR Our major aim in this project is to carry out the first comparative analyses across several lemurs genera and study the effect of habitat loss and fragmentation in the north and northwest of Madagascar, and to develop new genetic markers for this aim. Population sizes and densities have been estimated in the field for nocturnal lemurs (Microcebus and Lepilemur genera). Microcebus have been captured and biopsies collected. One paper is currently drafted on the density of Microcebus and Lepilemur in forests from the daraina region. Schematic representation of the structure of a bHLH dimmer that is complexed to DNA. From Bertrand, Castro and Guillemot, Nature Neurosciences, 2002.
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COLLABORATIONS Benoît Goossens (Cardiff University, UK) Michael Bruford (Cardiff University, UK) Benoît Goossens (Danau Girang Field Center, Kota Kinabalu, Malaysia) Nurzhafarina Othman (Universiti Malaysia Sabah, Malaysia) Marc Ancrenaz (Kinabatangan Orang-utan Conservation Project, Sabah, Malaysia) Isabelle Lackman-Ancrenaz (Kinabatangan Orang-utan Conservation Project, Sabah, Malaysia) Brigitte Crouau-Roy (Univ. de Toulouse, France) Christophe Thébaud (Univ. de Toulouse, France)
GOLDEN CROWN SIFAKA (PROPITHECUS TATTERSALLI). A species of lemur living in the small Daraina region on thevery north of Madagascar.
ORANG-UTANS (PONGO PYGMAEUS). From the Sepilok Rehabilitation Center, Sabah, Malaysia, in the north of Borneo (Credit: Reeta Sharma).
BORNEAN ELEPHANTSW (ELEPHAS MAXIMUS). In the area around the Kinabatangan River, in Sabah, Malaysia. (Credit: Reeta Sharma).
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NEUROBIOLOGY OF ACTION
LYMPHOCYTE PHYSIOLOGY
Head: Rui Costa
Head: Jocelyne Demengeot
PhD in Biomedical Research Universidade do Porto, Portugal
PhD in Cellular and Molecular Biology Université d’Aix-Marseille II, France
THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
We study the neurobiology of action in health and disease. To study actions is to study the way we do things, which is different than studying how we remember stimuli, or facts and events. Some actions are innate or pre-wired (like swallowing, breathing, even grooming). Others are learned through trial and error throughout life. We currently focus on understanding the processes mediating the latter. Our overall goal is to understand how changes in molecular networks in the brain modify neural circuits to produce experience-dependent changes in actions. In order to understand how actions are learned through trial and error, we subdivided our experiments in different components, or specific goals: Action initiation: how do we initiate and generate diverse actions (trial); Action improvement: how do we improve the accuracy and speed of actions (through trial and error): Actions and outcomes: how do we learn that particular actions lead to particular outcomes (goal of the action) and how do we form habits.
GROUP MEMBERS Vitor Paixão (Post-doc) Fatuel Aguilar (Post-doc) Cristina Afonso (Post-doc) Catherine French (Post-doc) Gabriela Martins (Post-doc) Eduardo Ferreira (PhD student) Pedro Ferreira (PhD student) Fernando Santos (PhD student) Ana Mafalda Vicente (PhD student) Albino Maia (Clinical Research Fellow) Rosalina Fonseca (Clinical Research Fellow) Ana Maria Vaz (Research Technician) FUNDING European Research Council Marie Curie International Reintegration Grant, European Commission Champalimaud Foundatoon, Portugal Fundação para a Ciência e a Tecnologia (FCT), Portugal
RAG MEDIATED DNA REARRANGEMENT We aim at formally establishing the frequency, efficiency and nature of cRSS ('cryptic Recombination Signal Sequences) in the genome, combining experimental, bio-informatic and mathematical approaches to test specific hypotheses and to perform unbiased large-scale analyses. We collaborate with five other groups at IGC presenting complementary expertise. The project required the development and improvement of several experimental tools before its full development. We improved our novel assay, reporter of Rag activity at chosen nucleotide sequences, now to allow for medium to large-scale screening. To allow for in vivo testing, we had developed a novel transgenic mouse model, where Rag activity can be induced in all tissues, by orally administered tamoxiphen. We confirmed that this novel model is amenable to test the effect of ectopic Rag activity, on both short and long term.
A growing body of evidence supports an important role of the basal ganglia in action initiation and selection, in skill learning, and in learning goal-directed actions and habits. Therefore, we centred our efforts on investigating the cortico-basal ganglia mechanisms underlying these three processes using an across-level approach, from molecules to circuits. We chose to implement this integrative approach in mice because they combine the power of genetics, a mammalian brain with canonical cortico-basal ganglia loops that can generate and propagate oscillatory activity, and the possibility of accurately quantifying simple behaviours like action initiation (with EMG recordings or using inertial sensors) and stereotypic skill learning, and more elaborate behaviours like goal-directed actions.
CORTICOSTRIATAL MECHANISMS UNDERLYING GOAL-DIRECTED ACTIONS AND HABITS Our goal is understanding the difference in the brain between intentional actions and habits or routines. We have uncovered that uncertainty increases the propensity for habit formation; investigated the relation between medial and lateral striatal circuits in controlling goal-directed actions versus habits and found that SNc but not VTA dopaminergic neurons are involved in habits. NEURAL MECHANISMS UNDERLYING THE GENERATION OF NOVEL ACTIONS This project aims to understand how new self-initiated actions are generated and how this ability is hampered in Parkinson´s disease. We have developed a new methodology to, in parallel, follow neural activity and the behaviour of mice with accelerometers.
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RESEARCH GROUPS
GROUP MEMBERS Marie Louise Bergman (Post-doc) Elodie Mohr (Post-doc) Andreia Lino (Post-doc) Marie Bonnet (Post-doc) Ricardo Paiva (PhD student) Sandra Gama Garcies (PhD student) Maria Espirito Santos (Research Technician) Catarina Martins (Research Technician) Rosa Maria Santos (Research Technician) COLLABORATIONS Jorge Carneiro, Vasco Barreto, Isabel Gordo, Karina Xavier, José Leal, Alekos Athanasiadis, Constantin Fesel, Maria Francisca Moraes Fontes (Instituto Gulbenkian de Ciência, Portugal) Manuel Villanova (Instituto de Ciências Biomédicas Abel Salazar, Portugal) Luis Graça, João Barata, António Jacinto, Leonor Sarmento (Instituto de Medicina Molecular, Portugal) Lucien Aarden (Sanquin Research Institute, The Netherlands) Montchillo Russo (Universidade de São Paulo, Brazil) Marc Dionne (King College London, UK) Virginia Rivero (Cordoba University, Spain) Chantal Mathieu (Catholic Univerity, Leuven, Belgium) Juan J Lafaille (Skirball Institute, NYU, USA) Santiago Zelenay (Institute for Cancer Research, London, UK) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal
IMMUNE REGULATION The overall aim of this project is the evaluation of the rules governing regulatory T cell (Treg) differentiation in the thymus and in the periphery, their maintenance and expansion as well as their domain of competences. The specific aims are:
Our research programme will hopefully shed light on the mechanisms underlying the diversity of actions we perform, the automatisation of actions and the generalisation of rules or ways to carry them out. Our research may also have important implications for understanding the relation between corticostriatal dysfunction and the symptoms of different neurodegenerative and psychiatric disorders. NEURAL MECHANISMS OF SKILL AND SEQUENCE LEARNING Understanding how novel actions are learned and consolidated as sequences of movements and skills are the main aims of this project. We have uncovered neural activity in nigrostriatal circuits related to the initiation and termination of novel action sequences.
We are concerned with those properties of the immune system that guarantee tissue integrity as well as tolerance to commensals and food antigens while maintaining the ability to mount efficient responses to infectious agents. We approach the cellular and molecular bases of immune regulation through the analysis of various mouse models, notably of spontaneous or induced autoimmune and immuno-pathological inflammation. Keeping in mind that the vertebrate immune system relies on the production of a very large diversity of antigen receptors through genomic rearrangement by the RAG recombinases, we also maintain a line of research assessing the consequences of deregulated RAG activity on genomic integrity and on lymphocyte homeostasis. Our interests merge within various collaborative works, notably addressing the efficiency of immunotherapies for Systemic Lupus Erythematosus, Rheumatoid-Arthritis and Type1 diabetes. Further afield, we are involved in multidisciplinary approaches related to the evolutionary origin of the immune system as well as to the evolution and ecology of the microbial flora.
SPECIFICITY OF CRE EXPRESSION IN in PVCre AND ChATCre MICE. A - Montage of images from an adult brain section through the striatum demonstrating YFP colocalisation with PV in the PVCre mouse line crossed with a ROSA26-YFP reporter mouse. B-G - The inset in dorsolateral striatum depicts the location from where the smaller images were obtained. B-D - The first column demonstrates PV immunoreactivity (in red; B), YFP expression (green; C), and colocalisation of both (yellow; D) in the PVCre-ROSA-YFP mouse striatum. E-G - The second panel shows ChAT immuno-reactivity (in red; E), YFP expression (green, F), and colocalisation of both (yellow; G) in a ChATCreROSA-YFP mouse striatum. Scale bars = (A) 500µm; (D) 125µm for (B-G). (by Gabriela Martins)
THE ROLE OF DIFFERENT STRIATAL CIRCUITS IN ACTION LEARNING. Left - Mice performing a behaviour task-walking on a rotating rodwhich requires action learning that depends on striatal circuits in the brain. Right - Identification of striatal medium spiny neurons of the direct pathway expressing D1 dopamine receptor (in red) and striatal medium spiny neurons of the indirect pathway expressing D2 receptor (in green). Note the two populations do not overlap.
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1. To establish the origin of the antigens that drive regulatory T cells; 2. Establishing the origin of regulatory T cell specific to strictly peripheral antigens; 3. Along with the hygiene theory, to test the role of the microbiota in modulating immune tolerance; 4. To assess the role of B cells and B cell products in the control of T cell homeostasis. We showed that peripherally administered antigens can gain access to the thymus and promote the differentiation of thymocytes into Foxp3+ cells: • We showed that Thymic epithelial cells alone are endowed with the specific ability to present and cross-present antigens to drive Treg differentiation; • We revealed that pregnancy associates with the de novo differentiation of fetus specific Foxp3+ cells, necessary for the mother's survival. We showed that immunogenic foreign antigens administrated in the foot-pad promote the de novo differentiation of immunogene-specific Treg, primarily in the thymus; • We established that lymphopenia promotes Foxp3 expression by peripheral T cells, a process restricted to recent thymic emigrants. We demonstrated that regular administration of the bacterial compound LPS prevents Type 1 diabetes in mice through the enhancement of regulatory T cells activities. We provided evidence that B cells control conventional and regulatory T cell number in the periphery but not their production in the thymus.
IGC ANNUAL REPORT ‘10
RESEARCH GROUPS
DIFFERENTIATION OF PERIPHERAL ANTIGEN SPECIFIC FOXP3+ REGULATORY T CELLS IN THE THYMUS. Transgenic mice for a T cell receptor gene specific for myelin basic protein were injected only once in the foot-pad with a mixture of Complete Freund Adjuvant and a myelin basic protein peptide. Shown is the Flow-cytrometric analysis of the antigen specific T cells in the Thymus and lymph nodes at different days post immunisation.
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PLANT MOLECULAR BIOLOGY
PLANT DEVELOPMENT
Head: Paula Duque
Head: José Feijó
PhD in Biology Universidade de Lisboa, Portugal
PhD in Cell Biology Universidade de Lisboa, Portugal
The Plant Molecular Biology group uses Arabidopsis thaliana as a model system to investigate how plants perceive and respond to environmental signals and endogenous developmental cues at the molecular level. In particular, we focus on the role of pre-mRNA splicing in the regulation of gene expression. The versatility of this mode of regulation suggests that it is likely to play an important contribution in ensuring the developmental plasticity and stress tolerance that are essential for plant survival. Another major ongoing project in the lab is examining the role of mutiple drug resistance (MDR) membrane transporters in plant resistance to chemical stresses such as herbicides and heavy metals.
GROUP MEMBERS Estelle Remy (Post-doc) Raquel Carvalho (PhD Student) Sofia Carvalho (PhD Student) Inês Barbosa (Research Technician; left August 2010) Rita Batista (Research Technician)
Research in the Plant Development group is concerned with developing integrated models of cellular growth and morphogenesis using the pollen tube as a biological model, ion dynamics as an experimental paradigm and theoretical modeling as an integrative tool.
COLLABORATIONS Ji He (The Samuel Roberts Noble Foundation, USA) John Brown (University of Dundee, UK) Elena Baena-González (Instituto Gulbenkian de Ciência, Portugal) Isabel Sá-Correia (Instituto Superior Técnico, Portugal)
We have characterised novel ion channels involved in pollen tube growth and morphogenesis, by means of imaging, electrophysiology, genetics and molecular biology. Furthermore, we contributed to or deciphered some of the genetic and cellular mechanisms behind pollen tube guidance and fertilisation in plants. Our group has provided novel insights into the transcriptional status of plant male gametes and its consequences for plant reproduction and improvement.
FUNDING Fundação para a Ciência e Tecnologia (FCT), Portugal
DETERMINING THE EPIGENETIC MECHANISM OF CENTROMERE PROPAGATION Using reverse genetics approaches in Arabidopsis thaliana, we are investigating the function of individual SR proteins in plant responses to different forms of abiotic stress. In addition, biochemical approaches are being employed in the identification of the physiological targets of these RNA-binding proteins to elucidate the precise molecular mechanisms underlying the functions of plant SR proteins in the adaptation to environmental changes. In support of our initial hypothesis, we have thus far shown that two plantspecific SR proteins play important roles in the response to environmental signals. Using reverse genetics, we have found that SR45, an Arabidopsis SR protein highly conserved throughout the plant kingdom, is a novel player in glucose signaling during early seedling development. Its mode of action involves downregulation of the abscisic acid (ABA) stress signaling pathway, via repression of both glucose-induced ABA endogenous accumulation and ABA biosynthesis and signaling gene expression. Epistasis analyses suggest a mechanism that is independent of the hexokinase 1 (HXK1) sugar sensor, and preliminary results indicate that SR45 modulates the stability of KIN10, a protein kinase involved in sensing/signaling of stress-associated energy deprivation. On the other hand, SCL30a defines a novel ABA signaling component that negatively regulates ABA responses during seed development and germination, controlling different aspects such as seed size, dormancy, ABA sensitivity and response to salt and drought stress. Thus, by reducing the sensitivity to ABA, the SCL30a protein positively regulates environmental stress tolerance during seed germination. RESISTANCE TO CHEMICAL STRESS IN ARABIDOPSIS: ROLE OF PLANT MULTIDRUG RESISTANCE MEMBRANE TRANSPORTERS TPO1 is a Saccharomyces cerevisiae plasma membrane MDR transporter belonging to the Major Facilitator Superfamily (MFS), which determines resistance to one of the most widely used herbicides worldwide, 2,4-dichlorophenoxyacetic acid (2,4-D). Using a candidate gene strategy, we have selected Arabidopsis genes exhibiting homology to TPO1 and increased expression upon exposure to 2,4-D for heterologous expression in yeast and functional analysis in plants. In collaboration with researchers at the Instituto Superior Técnico, we have found that one of these genes, belonging to the MFS, confers increased resistance to 2,4-D and other xenobiotic compounds - such as IAA (indole-3-acetic acid), Tl3+ and Al3+ - in yeast. Loss- and gain-of-function approaches in Arabidopsis are now showing that this MFS gene also confers resistance to 2,4-D and IAA in plants, confirming the effectiveness of the strategy employed and supporting our working hypothesis that plant MFS transporters play a role in 2,4-D resistance and MDR in general.
The members of the group have been pivotal in strengthening the imaging, transcriptomics and vibrating probe electrophysiology services of the IGC. We have several collaboration with theoretical, animal developmental, evodevo and other groups at the IGC, apart from external collaborations with research groups in Portugal and abroad.
IGC ANNUAL REPORT ‘10
COLLABORATIONS Ana Bicho, Ana Lourenço (REQUIMTE, Universidade Nova de Lisboa, Portugal) Alice Cheung (Univ Massachusstes, Amherst, USA) Gerhard Obermeyer (Univ. Salzburg, Austria) Matthew Gilliham (Univ Adelaide, Australia) Christophe Maurel (INRA- Montpellier, France) Rob Martienssen (Cold Spring Harbor Laboratory, USA) Keith Slotkin (Univ. Ohio, Columbus, USA) Liam Dolan (Oxford University, UK) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal
ELECTROPHYSIOLOGICAL CHARACTERISATION OF MEMBRANE TRANSPORTERS FROM ARABIDOPSIS THALIANA POLLEN TUBE In this project we are carrying out patch-clamp characterisation of chloridechannels in pollen protoplasts, as well as genetic and transport phenotype characterisation of three different classes of chloride channels expressed in Arabidopsis pollen. We established, for the first time, the existence of reliable and reproducible anion currents in pollen protoplasts of lily and Arabidopsis. These are grouped within three populations of currents, are sensitive to Ca2+ and show at least an equal affinity to chloride and nitrate. These might be the first bona fide chloride channels in plasma membrane of plant cells. Based on the electrophysiological profiles, we started a systematic screen of mutants of putative chloride channels.
The Arabidopsis sr45-1 mutant is hypersensitive to glucose during early seedling development.
A SYSTEMS APPROACH TO APICAL CELL GROWTH The aims of this project are the definition of electrical equivalent models based on the individual fluxes described; modelling of internal ion concentrations based on membrane activity, and the description of glutamate receptors as possible calcium channels in pollen. We established numerical methods to model how membrane activity will result in specific patterns of cytosolic free concentration of a given ion. We have calibrated these models using experimental data from tobbacco and lily. So far these models seem to be a good representation of ion dynamics for Ca2+ and pH. Assuming its correctness, the model predicts that observed proton fluxes at the level of the plasma membrane are sufficient to explain the cytosolic choreography of this ion. On the contrary, cytosolic free Ca2+ cannot be explained exclusively by the plasma membrane activity, intracellular sequestration is also needed. Pollen grains germinating in the stigma of Arabidopsis Thaliana.
The plant-specific SCL30a SR protein is expressed in the embryo during seed development in Arabidopsis.
RESEARCH GROUPS
GROUP MEMBERS Nuno Geraldo (Post-Doc) Claúdia Campos(Post-Doc) Ana Bicho (Post-Doc) Filipa Alves (Post-Doc) Kai Konrad (Post-Doc) Pedro Lima (PhD Student) Patricia Domingos (PhD Student) Ana Barbara Santos (PhD Student) Pedro Lima (PhD Student)
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Calcium oscillations in the Arabidopsis Thaliana pollen tube.
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YEAST STRESS
TELOMERES AND GENOME STABILITY
Head: Lisete Fernandes
Head: Miguel Godinho Ferreira
PhD in Biochemistry Universidade de Lisboa, Portugal
PhD in Cell Biology University College London, UK external website: http://sites.igc.gulbenkian.pt/telomere/tgs/Welcome.html
Adaptation and survival to intracellular and extracellular environmental challenges (stresses) are fundamental processes in all organisms. Microorganisms, in general, are widely exposed to oxidative environments such as those imposed by chemical/physical stress agents. Pathogens, in particular, are exposed to oxidative burst during phagocytosis. In fact, exposure to many fungicides and anti-cancer drugs generates oxidative stress. Similarly, exposure to temperatures below the optimal value has effects on the intracellular oxidative environment. Adaptation and survival depends on the accuracy and specificity of intracellular signal/stimuli propagation and efficient counteracting/compensatory response(s). Despite the adjustments of gene expression at different levels, remodeling of transcription by RNA polymerase II (pol II) is a crucial process under stress stimuli. Our group research aims to gather understanding of the molecular mechanisms of oxidative stress-signalling pathway(s), that culminate in discrete transcriptional events, involving two non-classical players as targets/signaling molecules in oxidative stress pathway - general transcription factors and folding machinery components. We are also interested in understanding adaptation from the population point of view.
GROUP MEMBERS João Coelho (PhD student) (left May 2010) Dora Pinto (MSc student) Ana Fátima Amorim (MSc student) Ana Filipa Martins (Trainee) COLLABORATIONS Isabel Gordo (IGC, Portugal) Martine Collart (University of Geneve, Switzerland) Milena B.P.Soares (Centro de Pesquisas Gonçalo Moniz/FioCruz & Hospital São Rafael, Salvador, Brazil)
INHIBITION OF GENOME INSTABILITY THROUGH TELOMERE PROTECTION We developed a novel direct assay for telomere fusions in fission yeast using a linear plasmid. We validated this assay using known telomere protection mutants (such as trt1Δ) and identified the DNA repair mechanisms underlying chromosome-end fusions. Unexpectedly, we observed telomere fusions in wt cells which had occurred between DNA ends still containing telomere sequences, albeit shorter (less than 120bp). We were able to show that, although at very small frequency (≈10-8 events per generation), wt cells undergo telomere fusions that can lead to dicentric chromosomes and genome instability. We used the novel telomere fusion assay in a random mutagenesis screen hoping to identify temperature sensitive (ts) mutants in telomere protection. We were able to identify several mutants that underwent telomere fusions, but no ts mutants - an essential prerequisite for identification of the underlying mutation.
MOLECULAR MECHANISMS BRIDGING PROTEIN FOLDING AND TRANSCRIPTION ACTIVATION GimC, also designated prefoldin, is a cytoplasmatic complex composed of 6 distinct subunits (Gim1-Gim6 and Pfd1-Pfd6 in Saccharomyces cerevisiae and mammals, respectively) that promotes the formation of functional actin and tubulin, essential components of the cytoskeleton. GimC binds to nascent chains of these substracts, delivering them, after completion, to the chaperonine TRiC/CCT for efficient folding. However, the Gim proteins are not essential and data in the literature suggest alternative functions for several of the GimC subunits, e.g., Archaea contains a complex homologue of prefoldin and inherent substrates do not include actin/tubulin. Our results with gim mutants pinpoint different activities of each Gim subunit in the regulation of transcription of stress-specific genes. We showed that Gim2 has opposite effects on the stress-induced transcription factors, Yap1 and Msn2, inherent activation potential. Yap1 is a transactivator that regulates transcription upon oxidative stimuli and in response to unrelated drugs; Msn2 also responds to osmotic stimuli. In this context, we aimed to map the Gim2 function in gene transcription by RNA polymerase II. Assays were launched to dissect if both transcription factors, Yap1 and Msn2, directly bridge Gim2. In order to ascertain the contribution of the remaining Gim subunits for Yap1 and Msn2 inherent activation potential as well as putative protein-protein interactions, biological material (yeast strains and plasmids) were constructed.
IGC ANNUAL REPORT ‘10
GROUP MEMBERS Catarina Henriques (Post-doc) Clara Reis (Post-doc) Tiago Carneiro (Post-doc) Hugo Almeida (PhD Student) Ana Teresa Avelar (PhD Student) Joana Nabais (MSc Student) María Gallo (External MSc Student) Inês Tenente (External MSc Student, Co-supervised with A Jacinto, IMM) COLLABORATIONS Toru M. Nakamura (University of Illinois at Chicago, USA) FUNDING Association for International Cancer Research, UK Fundação para a Ciência e a tecnologia (FCT), Portugal
END-PROTECTION AND DNA REPAIR AT S. pombe TELOMERES We established that MRN function in non-homologous end-joining (NHEJ) of dysfunctional telomeres was related to its ability to bridge DNA ends together. This result provided a rationale for observed differences: plasmid-ends are never far apart (as they are physically constrained by the plasmid DNA), whereas chromosome-ends may need additional requirements in bridging the gap. To test this idea, we developed an improved plasmid NHEJ assay and observed that MRN complex was required for NHEJ in this setup. These results will help to reconcile conflicting data in the literature and provide mechanistic insights for MRN as a central platform for both HR and NHEJ repair.
TRANSACTIVATOR Yap1: CROSSROADS OF COLD AND OXIDATIVE STRESS SIGNALING PATHWAYS The cytoskeleton network is a well-known target of oxidative and cold stimuli as well as structurally essential for proper intracellular mobility of transcription factors. Yap1 and Yap4, two bZips from the same family, are linked with these stress stimuli and cytoskeleton. By analysing Yap1 (and Msn2) activity under oxidative stimuli (triggered by hydrogen peroxide, e.g.), our previous results uncouple actin from microtubules contribution. In order to define a broader biologically relevant model for the cytoskeleton contribution in transcriptional oxidative response, we aim to evaluate the effects of drugs used in pharmacological therapy. The selection of drugs, in collaboration with Milena P.B. Soares, of the Centro de Pesquisas Gonçalo Moniz/FioCruz, Brazil, was undertaken.
RESEARCH GROUPS
Telomeres protect the ends of linear eukaryotic chromosomes from being recognised as deleterious DNA double strand breaks (DSBs). Just a single DSB is able to stop cell cycle progression and activate repair processes. In contrast, all telomeres prohibit DNA repair, as it may lead to chromosomeend fusions - a source of genomic instability and a step in tumourigenesis. This fundamental function fades as telomeres get progressively shorter in cells of older people, thus limiting the capacity of tissue renewal and increasing the probability of cancer. Our aim is to understand how telomeres block DNA repair and, when this function fails, how cells respond to unprotected chromosomes. Using fission yeast as a model system, we plan to identify key players and the mechanisms underlying these events. This way, we hope to provide important insights into the initial stages of cancer formation as well as specific candidate targets for future therapeutic intervention.
IDENTIFICATION OF ANTI-CHECKPOINT PROTEINS IN FISSION YEAST TELOMERES We showed that checkpoint activation at telomeres does not lead to cell cycle arrest, even though ATR and ATM are activated and DNA repair is ongoing. We showed that the chromatin binding protein Crb2/53BP1 is unable to be maintained at chromosome-ends, thus severing the checkpoint signaling pathway. We further showed that this telomere function is under the control of the ssDNA telomere binding protein Pot1 and its partner Ccq1, a protein involved in chromatin remodeling. In absence of either protein, checkpoints are promptly triggered at telomeres. We propose a model whereby telomeres normally initiate checkpoints every S phase, but signaling is interrupted due to local chromatin status. GENOME-WIDE ANALYSIS OF TELOMERE PROTECTION IN S. pombe We started using the fission yeast whole genome deletion library looking for telomere protection factors by southern blot on the available Å3000 viable mutants. All telomere protection mutants described to date are non-essential, thus this strategy should produce several remaining players. Presently, we have screened 80% of the deletion library.
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IGC ANNUAL REPORT ‘10
RESEARCH GROUPS
We use fission yeast to understand the molecular nature of telomere protection (in the top two pictures, the sub-telomeres of chromosome III are stained in green, highlighting a telomere fusion. Red SPB and blue - DNA). .
We use zebrafish to study the consequences of telomere dysfunction in cancer and ageing (the two pictures show crypts and villi of the intestine with proliferating cells in red and apoptotic cells in green. Blue - DNA).
This scheme highlights the chromatin nature of telomere protection, as described in our recent paper in Nature.
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COLLECTIVE DYNAMICS
EVOLUTIONARY BIOLOGY
Head: Gabriela Gomes
Head: Isabel Gordo
PhD in Mathematics University of Warwick, UK
PhD in Biology University of Edinburgh, UK external website: http://eao.igc.gulbenkian.pt/EB/index.html
We study collective phenomena, such as self-organisation, criticality, and pattern formation, arising from spatial and temporal constraints in physical and biological systems, with a current focus on infectious disease ecology and evolution. The central theme of our research derives from a conceptual model of partial immunity whose collective outcome - the reinfection threshold - underlies a phenomenological transition in epidemic dynamics, with practical implications ranging from extreme geographical variability in the effect of vaccination programmes to destabilised transmission favouring polymorphism in antigenically diverse pathogens. We are interested in refining concepts and methodologies by performing specific experiments in the laboratory and in natural populations. MOLECULAR EPIDEMIOLOGY OF Mycobacterium tuberculosis IN PORTUGAL: IMPLEMENTING AND ANALYSING A DATABASE We aim to implement and deploy a system for information and molecular analysis of tuberculosis. The IGC Genomics Unit expanded, the genotyping of mycobacteria causing tuberculosis, from 65 to 90 SNPs, and characterised over one thousand strains. The IGC Bioinformatics Units completed the database development and implemented a prototype of a web-based user interface. The system (SIAM-TB) is ready for deployment. EXPLORING PATHOGEN DIVERSITY IN DISEASE EPIDEMIOLOGY AND VACCINE RESEARCH The aim of this project is to unravel the molecular bases and epidemiological significance of immunity in order to guide vaccine design and deployment. A model for the dynamics of pneumococcus transmission at the level of genotype has been developed and parameterised by daycare centre colonisation data previously collected by Raquel Sá-Leão. A model to infer distributions of susceptibility in host populations from dose-infection curves has been implemented for application to experimental data.
GROUP MEMBERS Sander van Noort (PhD Student) Bruno Ceña (Trainee) Delphine Pessoa (Trainee) COLLABORATIONS Carlos Penha-Gonçalves, José Pereira-Leal, Carlos Penha-Gonçalves, Lounes Chikhi, Ana Godinho (Instituto Gulbenkian de Ciência, Portugal) Anabela Miranda (Instituto Nacional de Saúde Dr Ricardo Jorge, Portugal) Raquel Sá-Leão (Instituto de Tecnologia Química e Biológica, Portugal) Diogo Pinheiro (Instituto Superior de Economia e Gestão, Portugal) Cláudia Codeço (Fundação Oswaldo Cruz, Brazil) Alessandro Vespignani (Institute for Scientific Interchange, USA) Lewi Stone (Tel Aviv University, Isreal) Dirk Brockmann (Max Planck Institute Gottingen, Germany) Ronald Smallenburg (Grote Griepmeting, The Netherlands) John Edmunds (London School of Hygiene and Tropical Medicine, UK) Olof Nyrén (Swedish Institute for Infectious Disease Control, Sweden) Marc van Ranst (Rega Institute for Medical Research, Belgium) Shlomo Havlin (Bar Ilan University, Isreal) Stefano Merler (Fondazione Bruno Kessler, Italy) Daniele Miorandi (Center for Research and Telecommunication Experimentation for NETworked communities, Italy) Mário Silva (Faculdade de Ciências de Lisboa, Portugal) Maurício Barreto (Instituto de Saúde Coletiva, Universidade Federal da Bahia, Brazil) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal European Commisison Framework Programme 7
DEVELOPING THE FRAMEWORK FOR AN EPIDEMIC FORECAST INFRASTRUCTURE (EPIWORK) The goals of this project are to develop the framework for an epidemic forecast infrastructure. A transmission model of influenza was fitted to influenza-like illness incidence data, as monitored from 2003 to 2010 by two independent symptomatic surveillance systems (Influenzanet and EISN) in three European countries. New correlations were found between weather conditions and influenza symptoms. The implications for public health management of influenza and other seasonal infections were described.
All natural populations have to adapt to new environments. Knowledge of the genetics of adaptation should provide the centrepiece of a unified theory of evolution. Despite its extreme importance, the process of adaptation is far from being understood. For example: What is the rate at which positive Darwinian selection occurs? Does the rate of adaptation depend on genetic background? What is the distribution of fitness effects of mutations? Does adaptation involve the fixation of mutations with small or large effects? How do mutations interact? What are the relative costs and benefits in bacterial cells with high mutation rates? These are some of the questions that we try to address. RATES OF MUTATIONS IN THE PROTOZOA Tetrahymena thermophila The aim is to estimate the rate and effects of mutations in the macro and micro nucleous of Tetrahymena thermophila. We found a high level of extinction in a mutation accumulation experiment in Tetrahymena thermophila, which is naturally a sexual species and carries two different nuclei in the same cell; and we found a much slower rate of extinction in Tetrahymena pyriformis, which is completely asexual and does not carry a micronucleous.
COLLABORATIONS Guillaume Martin (University of Montpellier, France) Philip Gerrish (Universidade de Lisboa, Portugal) Jocelyne Demengeot, Karina Xavier, Migeul Godinho Ferreira (Instituto Gulbenkian de Ciência, Portugal) Paulo Campos (Universidade Federal Rural de Pernambuco, Brazil) Lilia Perfeito (University of Cologne, Germany) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal European Research Council
ANTIBIOTIC RESISTANCE AND THE GEOMETRY OF COMPENSATORY EVOLUTION In this project we aim to estimate the rate and distribution of effects of mutations that compensate for the costs of antibiotic resistances. We find that beneficial mutations, which can contribute to compensatory evolution, occur at very high rates, of the order of 10^5 per genome per generation, cause an average fitness increase of 2.6% and 3.6%, depending on the population distance to the optimum, and can be detected within a few tens of generations. We also find that the effects of mutations are well approximated by a beta distribution. Our results support the expectations of Fisher's geometrical model in the statistical laws governing adaptation, provide the first description of the distribution of beneficial mutations that compensate for antibiotic resistances bearing different costs and have therefore important implications to our understanding of the spread of antibiotic resistance in bacteria. ADAPTATION WITHIN ECOSYSTEMS We aim to describe the adaptive strategies that Escherichia coli can evolve to face predation by macrophages, and to compare rates of adaptation under strong biotic interactions. We studied the dynamics of adaptation of Escherichia coli when facing predation by macrophages to tackle these questions and test evolutionary hypotheses. Our results show a higher rate of adaptive evolution in the presence of predation and a higher level of variation within and between bacterial populations under the pressure imposed by the macrophages. We find that in a few hundred generations bacteria can evolve a remarkable resistance to macrophages. Strikingly, diversity within populations is very rapidly observed and is characterised by the emergence of clones with different morphologies and with traits similar to those found in pathogenic bacteria. We also demonstrate that there are global strategies that provide bacteria a fitness advantage when facing different predators. These findings have important bearings for both evolutionary biology and human health.
MOLECULAR AND ENVIRONMENTAL EPIDEMIOLOGY OF TUBERCULOSIS AND DENGUE Within this project we aim to capacitate epidemiological research through the transfer of science and technology between Portugal and Brazil. An internet-based system to monitor dengue epidemics in Salvador (DengueWeb) has been launched. A collection of Mycobacterium tuberculosis strains from Salvador have been genotyped by the IGC Genomics Unit, in conformity with an ongoing programme for genotyping strains collected in Portugal.
GROUP MEMBERS Ana Margarida Sousa (Post-Doc) Patricia Brito (Post-Doc) Sandra Trindade (PhD student) Migla Miskinyte (PhD student) Tiana Gonçalves (PhD student) Joana Antunes (Research Technician) João Batista (Research Technician)
Escherichia coli evolving with macrophages.
A fitness landscape.
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IGC ANNUAL REPORT ‘10
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ACTIN DYNAMICS
EPIGENETIC MECHANISMS
Head: Florence Janody
Head: Lars Jansen
PhD in Developmental Biology Université de la Mediterranée, France
PhD in Molecular Genetics Leiden University, The Netherlands
The actin cytoskeleton controls a large number of cellular processes. Most studies that address how the actin microfilament system is regulated use in vitro assays or cells in culture, which allowed insight into the main classes of cytoskeletal regulators and their likely mechanism of action on actin. However, in cells in culture, most actin cytoskeletal genes have a cell-type specific function and it is also likely that many do not affect morphology of single cells but affect cells within a tissue. This suggests that within each cell type, the actin cytoskeleton adopts a specific organisation required to perform a particular function.
GROUP MEMBERS Estelle Remy (Post-doc) Raquel Carvalho (PhD Student) Sofia Carvalho (PhD Student) Inês Barbosa (Research Technician; left August 2010) Rita Batista (Research Technician)
Using Drosophila as a model system, which allows us to manipulate gene expression with relative ease, we aim to understand how cytoskeletal organisation is regulated in distinct epithelia and characterise the role of specialised filamentous actin-based structures. Our work shows that the actin cytoskeleton is a central organelle, which regulates intracellular signal transduction pathways involved in growth control and cell differentiation. We propose that particular actin-based structures allow cells to respond appropriately to signal sent by their neighbours, in this way preventing conflicts amongst cells within cellular communities and tumor development.
FUNDING Fundação para a Ciência e Tecnologia (FCT), Portugal
COLLABORATIONS Ji He (The Samuel Roberts Noble Foundation, USA) John Brown (University of Dundee, UK) Elena Baena-González (Instituto Gulbenkian de Ciência, Portugal) Isabel Sá-Correia (Instituto Superior Técnico, Portugal)
DACHSHUND PROPAGATES RETINAL DIFFERENTIATION BY PROMOTING CELL SHAPE CHANGES AND HIPPO SIGNALLING ACTIVITY The goal of this research project is to understand how the dynamics of the actin cycle is regulated to promote the change in cell shape in the morphogenetic furrow and trigger retinal differentiation. The nuclear protein Dachshund is the most downstream element among the known Retinal Determination Gene Network. We found that Dac is not required for cell fate determination but promotes cell shape changes required for proper differentiation of the retina. Moreover, Dac ensures that cells respect the developmental imposed-cell cycle arrest by triggering Hippo signaling activity in the determination zone, where it is highly expressed. Based on the molecular mechanism that underlies Dac function in the restriction of proliferation in cancer cells, our view is that Dachshund regulates Hippo signaling activity by inhibiting the transcriptional activity of the Scalloped-Yorkie complex.
IGC ANNUAL REPORT ‘10
RESEARCH GROUPS
GROUP MEMBERS Luis Valente (Post-doc) Mariana Silva (PhD student) Mariluz Gomez (PhD student) João Mata (Research Technician) Dani Bodor (Trainee) COLLABORATIONS Helfrid Hochegger (Sussex Centre for Genome Damage and Stability, UK) Don W. Cleveland (Ludwig Institute for Cancer Research, San Diego, USA) Daniel R. Foltz (University of Virginia, USA) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal
DETERMINING THE EPIGENETIC MECHANISM OF CENTROMERE PROPAGATION The aims of this project are the determination of the cell cycle control mechanism of centromere assembly, the development of fluorescent pulse labelling to determine the turnover and dynamics of centromere complex members, and the identification of factors that control deposition of the histone H3 variant CENP-A into centromeric chromatin. Earlier work suggested that mitosis may be an obligate prerequisite for assembly of nascent CENP-A in early G1 phase. In the initial stages of this project we have shown that mitotic passage is in fact, dispensable for CENP-A loading. Treatment of cells in G2 phase with cyclin dependent kinase (CDK) inhibitors induces rapid assembly of newly synthesised CENP-A at centromeres. In addition we have recapitulated CDK control of CENP-A assembly in chicken DT40 cells with genetically defined mutations in CDK1 and 2 and show that these are sufficient to restrict CENP-A assembly to G1 phase. Based on this and several other observations we are building a model that provides an important insight into the molecular coupling of cell cycle progression and centromeric chromatin propagation which forms the basis for the epigenetic nature of the centromere. In addition we have successfully developed genome engineering tools for CENP-A and have developed a novel rapid method to construct human fluorescent knockin cell lines. We are currently using these lines to quantify centromere protein copy number.
ACTIN-CAPPING PROTEIN AND THE HIPPO PATHWAY REGULATE F-ACTIN AND TISSUE GROWTH IN DROSOPHILA The goal of this project is to gain insight on how the dynamics of the actin cycle is regulated to prevent tumour formation. The conserved Hippo tumor suppressor pathway is a key kinase cascade that controls tissue growth by regulating the nuclear import and activity of the transcription co-activator Yorkie. Our work reveals an interdependency between Hippo signalling activity and actin filament (F-actin) dynamics in which actin-Capping Protein and Hippo pathway activities inhibit F-actin accumulation, and the reduction in F-actin in turn sustains Hippo pathway activity, preventing Yorkie nuclear translocation and upregulation of proliferation and survival genes. ACTIN CAPPING PROTEIN ACTS AS A TISSUE-SPECIFIC TUMOR SUPPRESSOR MODULE IN COOPERATION WITH ONCOGENIC MUTATIONS This project aims to understand how the dynamics of the actin cycle is regulated to prevent tumour formation. Most mammalian neoplasias are likely to originate from cooperative interactions between both tumor suppressors and oncogenes. We provide evidences that in cooperation with oncogenic mutations, the two cytoskeletal genes, Capping Protein α and β, act as tumor suppressor genes in restricted Drosophila epithelia. The Capping Protein module experts its tumor suppression function by stabilising the DE-Cadherin/Armadillo complex at Adherens Junctions and by preventing upregulation the DE-Cadherin gene. Increased DE-Cadherin levels would otherwise provide an active signal, which triggers JNK-mediated apoptosis or JNK-mediated proliferation when cells are prevented to die.
A single zygote differentiates into approximately 200 different cell types that, despite being genetically identical, maintain their cellular identity through mitotic divisions. Therefore, in addition to the genomic information embedded in the primary DNA sequence, epigenetic information is propagated as well, that “memorises” gene activity states and specific chromatin structures across somatic division and sometimes even across generations. Epigenetic inheritance forms the basis for many aspects of biology that includes development, gene regulation and disease. Several molecular components such as histone proteins and modifications thereof have been implicated in this process but in most cases we don’t understand the logic of how something other than DNA can be faithfully duplicated when a cell divides. We have a broad interest in how this works. We are using molecular genetic and cell biological tools with a focus on novel fluorescent labeling techniques, high-end microscopy and the latest tricks in genetic engineering of human cells to tackle a wide range of problems in this emerging and fascinating area of biology.
Model for the role of the actin cytoskeleton in intracellular signal transduction pathway.
HISTONE VARIANT ASSEMBLY AND MAINTENANCE ACROSS THE CELL CYCLE Within this project we aim to develop biochemical tools to track histone dynamics at molecular resolution across multiple cell divisions. Furthermore, we aim to determine the CENP-A nucleosome structure across the cell cycle and histone H3.3 turnover at gene resolution. Our initial focus has been to develop a robust protocol to detect and isolate biochemical quantities of in vivo pulse labeled histone proteins. We have now achieved proof of principle and are in the process of analysing histone turnover in relation to the cell cycle at epigenetically relevant loci that include the centromere and active genes.
Dac mutant cells (GFP negative cells, A-D or GFP positive cells, E, in green) can differentiate into photoreceptors cells (neuronal marker, Elav in magenta, A, A’), but show a delay in the Morphogenetic Furrow (MF) progression (Hh signaling transducer, Cubitus Interruptus (Ci) marks the MF in magenta, B, B’). Posterior to the Second Mitotic Wave, the last round of proliferation, dac mutant cells can re-enter in S phase as displayed by the incorporation of BrdU (magenta, C, C’), partially due to the maintenance of high levels of CycE (magenta, D, D’). This phenotype associated to the SMW mimics the lost of expanded, known to act upstream of Hippo signaling pathway. Indeed, dac mutant cells activate Hippo-target genes: CycE (magenta, D, D’) and diap1 (Diap1-lacZ in magenta E, E’).
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Indian Muntjac cells in mitosis stained for centromeres (green) and microtubules (red) visualising the process of chromosome capture and segregation by the mitotic spindle.
Novel fluorescence activated cell sorting based method to isolate rare, genome engineered human somatic cell clones.
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TISSUE MORPHOGENESIS
ORGANOGENESIS
Head: Mathias Koeppen
Head: Joaquín Rodríguez León
PhD in Cellular and Molecular Biology University of Wisconsin, USA
PhD in Biological Sciences University of Extremadura, Spain
Our focus is on the analysis of fundamental mechanisms of tissue morphogenesis in the zebrafish embryo, using high-resolution live microscopy in combination with genetic and embryological techniques. Specifically, we are interested in the morphogenetic behavior of the embryonic surface epithelium, the enveloping layer. During the first few hours of zebrafish development, this tissue enwraps and seals the embryo in a process called epiboly. This process is of general interest, since it has many similarities to the process of wound healing. In both cases, the epithelial sheet migrates in a highly coordinated fashion to close an epithelial discontinuity. Remarkably, both morphogenetic processes are driven by an acto-myosin cable that operates as a purse string that seems essential to the normal progression of tissue movement, and ultimately to blastopore/ wound closure. In order to understand the molecular mechanisms underlying the temporal and spatial organisation of the actin-myosin cable and its interconnections with epithelial cells, the laboratory pursues two main lines of investigation:
GROUP MEMBERS Ana Cristina Silva (Post-doc) Ana Cristina Borges (Post-doc) COLLABORATIONS António Jacinto (Instituto Medicina Molecular, Portugal) FUNDING Fundação para a Ciência e Tecnologia (FCT), Portugal
ROLE OF STEMNESS GENES DURING THE FORMATION OF COMPLEX ORGANS This project is devoted to elucidate how stemness genes contribute to proper morphogenesis of complex organs. Using the chicken embryo as a model we will work to find a link between oct4 activity and limb development. We have found evidences that oct4, required to establish and maintain the pluripotent cell population necessary for embryogenesis in mouse and human, controls the proliferative balance within the AER cells. Overexpression of otc4 in the limb ectoderm disrupts the cell death/proliferation ratio and this activity is under the control of the wnt-canonical pathway. We have also found a special localisation and behaviour of proliferating cells in the AER in response to oct4 activity. We therefore describe a role for oct4 as a factor which is able to maintain a niche of cells that is responsible for the renewal of the AER.
1. Analysis of the cellular and molecular mechanisms that control the spreading and sealing of the enveloping layer; 2. Study of wound healing in the zebrafish, during early developmental stages. DYNAMIC ANALYSIS OF WOUND Healing Morphogenesis IN ZEBRAFISH In particular we aim to connect the phenomenology of wound-margin shortening to the underlying cytoskeletal mechanics and genetic regulatory networks. We see embryonic wound healing as a process of epithelial re-sealing and an extension of normal morphogenesis - one where we can use variations in the tissue/wound geometry to investigate the full range of capabilities of the systems that generate and regulate morphogenetic/wound-healing forces. In collaboration with the laboratory of António Jacinto at the Instituto de Medicina Molecular (IMM), in Lisbon, we are establishing a laser-based wound healing assay of the surface epithelium of the zebrafish embryo. By coupling the laser-microsurgery system with high-resolution live imaging, we were able to visualise the dynamics of the healing process in a vertebrate model system, for the first time. Taking advantage of zebrafish imaging and genetic manipulation possibilities, we are beginning to characterise the molecular basis of vertebrate wound healing. Funded by FCT.
Our group focuses on the study of the cellular and molecular mechanisms controlling limb development and fin regeneration. We are trying to understand how the main signaling centre during limb development, the Apical Ectodermal Ridge (AER), is established and maintained through development and how different molecules, namely those related to stemness, are involved in these processes. Also, we have developed a line of research directed to depict how ion dynamics can control limb development, digit differentiation and fin regeneration. In these studies we use the chicken and zebrafish embryos as well as adult zebrafish as animal models.
Tight Junction markers in the zebrafish enveloping layer (EVL) during epiboly. Red marks Claudin-1; Green is ZO-1.
CYTOSKELETAL DYNAMICS DURING ZEBRAFISH EPIBOLY We are investigating the molecular control of enveloping layer epiboly, with a specific focus on the cytoskeleton. Past work suggested a mechanism bywhich a contractile actin “cable” drives the epiboly movement. Here we are addressing the mechanism that assembles this contractile structure, focusing specifically on the interaction between the actin and microtubule networks. Live confocal imaging and functional analysis revealed that actin undergoes long-range streaming within the embryo towards the contraction zone, possibly facilitated by the microtubule network. Drug-based inhibition of the microtubule network impairs actin recruitment and slows the progression of epiboly. This highlights the importance of global cytoskeletal dynamics during embryo morphogenesis.
IGC ANNUAL REPORT ‘10
ION DYNAMICS DURING FIN REGENERATION The aim of this project is to link ion dynamics and the molecules that control these processes during fin regeneration. We measured the chloride and sodium fluxes and the electrical current before and after amputation in the different stages of regeneration to characterise its profiles. As expected, immediately after amputation the injury potential occurs, but after wound healing the profile of chloride reveals an active process of fluxes that predicts regeneration. The sodium profile did not show influxes at the time of blastema formation and in ulterior stages. An interesting bioelectrical pattern was detected in which a higher efflux in the ray than interray is observed. Another part of this study was the pharmacological assays against putative chloride and sodium channels. Inhibition of chloride dynamics did not show an important role, but when NaV channels are inhibited we obtained results confirming the importance of sodium influx.
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COLLABORATIONS Yolanda Gañán Presmanes, Domingo Macías Rodríguez (University of Extremadura, Spain) Michael Levin (Tufts University, USA) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal
ION DYNAMICS DURING FIN REGENERATION The aim of this project is to link ion dynamics and the molecules that control these processes during fin regeneration. We measured the chloride and sodium fluxes and the electrical current before and after amputation in the different stages of regeneration to characterise it profiles. As expected, immediately after amputation the injury potential occurs, but after wound healing the profile of chloride reveals an active process of fluxes that predicts regeneration. The sodium profile did not show influxes at the time of blastema formation and in ulterior stages. An interesting bioelectrical pattern was detected in which a higher efflux in the ray than interray is observed. Another part of this study was the pharmacological assays against putative chloride and sodium channels. Inhibition of chloride dynamics did not show an important role, but when NaV channels are inhibited we obtained results confirming the importance of sodium influx.
Dynamics of epithelial (EVL) wound healing in the zebrafish embryo. Green marks actin.
RESEARCH GROUPS
GROUP MEMBERS Ana Catarina Certal Afonso (Post-doc) Ana Raquel Tomás (External PhD student) Joana Monteiro (External PhD student) Rui Castanhinha (PhD Student) Ana Rita Aires (Research Technician) Fernando Ferreira (MSc Student) Rita Félix (MSc Student) Diana Pires (MSc Student)
Double in situ Hybridisation for fgf8 (re) and msx1 (blue) after Oct4 overexpression.
Immunohistochemistry for atp6v1a in a regenerating fin 24 hours after amputation.
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SYSTEMS NEUROSCIENCE
PATTERNING AND MORPHOGENESIS
Head: Zachary Mainen
Head: Moises Mallo
PhD in Neurosciences University of California, USA external website: http://neuro.fchampalimaud.org/research/mainen/
PhD in Biochemistry and Molecular Biology Universidade de Santiago de Compostela, Spain
THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
We are interested in understanding the principles underlying the complex adaptive behaviour of organisms. Starting with quantitative observations of animal behaviour, we aim to integrate quantitative cellular and systems level experimental analysis of underlying neural mechanisms with theoretical, ecological and evolutionary contexts. Rats and mice provide flexible animal models that allow us monitor and manipulate neural circuits using electrophysiological, optical and molecular techniques. We have made progress using highly-controlled studies of a simple learned odor-cued decision task and are extending our focus toward more complex behaviours. Projects in the lab are wide-ranging and continually evolving. Current topics include: 1. Olfactory sensory decision-making; 2. The function of the serotonin system; 3. The role of uncertainty in brain function and behaviour.
GROUP MEMBERS Eric Dewitt (Post-doc) Magor Lorincz (Post-doc) Hope Johnson (Post-doc) Masayoshi Murakami (Post-doc) Guillaume Dugué (Post-doc) Thiago Gouvêa (PhD Student) Niccolò Bonacchi (PhD Student) Ana Rita Fonseca (PhD Student) André Mendonça (PhD Student) Maria Inês Vicente (PhD Student) Patricia Correia (PhD Student) Sara Matias (PhD Student) Gil Costa (PhD Student) COLLABORATIONS Adam Kepecs (Cold Spring Harbor Laboratory, USA) Alex Pouget (University of Rochester, USA) Matthieu Luis (Centre for Genomic Regulation, Barcelona)
OPTOGENETIC IDENTIFICATION AND CONTROL OF SEROTONIN NEURONS IN BEHAVING ANIMALS By selectively monitoring, stimulating or inhibiting serotonin neurons using optogenetic methods, we aim to test specific hypotheses concerning the role of serotonin in brain function and behaviour. We have focused on validating and improving our techniques for expressing light-gated channelrhodopsin-2 in 5-HT neurons. We also produced a vector for expressing the calcium sensor GCaMP3 in 5-HT neurons and a system for measuring activity of 5-HT neurons in behaving animals.
FUNDING European Research Council Human Frontiers Science Programme Champalimaud Foundation, Portugal Fundação Bial, Portugal
OLFACTORY OBJECTS AND DECISIONS: FROM PSYCHOPHYSICS TO NEURAL COMPUTATION We aim to unravel the neural mechanisms leading to complex olfactory object perception and recognition. We will do so by combining computational modeling approaches with electrophysiological recordings from rats performing several different olfactory decision tasks. We compared speed-accuracy trade-offs (SATs) in odor detection and categorisation and found large differences between tasks, demonstrating that SAT is problem-specific and suggesting that the locus of performance-limiting noise is a critical variable.
1. How timing of actions is determined in the premotor cortex; 2. How selection of one action among multiple options is achieved in the premotor cortex.
EVALUATING THE RELIABILITY OF KNOWLEDGE: NEURAL MECHANISMS OF CONFIDENCE ESTIMATION We aim to investigate the computation of decision uncertainty through inactivation and electrophysiological recordings on the olfactory system of rats performing an olfactory categorisation task and use these data to constrain a computational model for decision-making and confidence estimation. "We have developed a modified confidence reporting task that allows us to disambiguate key variables related to the decision process and plan to study function of the olfactory tubercule, an early olfactory structure that we hypothesise is important in olfactory decision-making.
IGC ANNUAL REPORT ‘10
RESEARCH GROUPS
GROUP MEMBERS Jennifer Rowland (Post-doc; left May 2010) Filipa Moraes (PhD Student; left March 2010) Tânia Vinagre (PhD Student) Arnon Jurberg (PhD Student) Ana Nóvoa (Research Technician) Isabel Guerreiro (Trainee) Andreia Nunes (Trainee) Sofia Pereira (Trainee; left September 2010) COLLABORATIONS Sara Monteiro (Instituto Superior de Agronomia, Portugal) FUNDING Fundação para a Ciência e Tecnologia (FCT), Portugal
MOLECULAR NETWORK DOWNSTREAM OF Hox GENES TO CONTROL FORMATION OF THE VERTEBRATE AXIAL SKELETON We want to identify the downstream targets of Hox group 10 and 6 genes that mediate their control of somite differentiation, and how expression of these genes is controlled. We have previously shown that Myf5 and Myf6 expression are controlled by Hox genes of groups 6 and 10, specifically in the hypaxial myotome. We have now shown that simultaneous inactivation of both Myf5 and Myf6 is required to block rib formation. We have also been able to rescue the rib-less phenotype of the Hoxa10-expressing transgenics by providing Myf6 in the hypaxial myotome using a specific Pax3 enhancer, thus further supporting the Hox/Myf connection in the context of rib development. Finally, we showed, using ChIP, that Hox6 and Hox10 proteins bind the Myf5 hypaxial enhancer in vivo, suggesting a direct regulation of Myf genes by Hox proteins. THE ROLE OF SPECIFIC PEPTIDE MOTIFS AND POSTRANSLATIONAL MODIFICATIONS IN ACTIVITY OF Hox GROUP 10 GENES We want to determine the role of Hox group 10-specific protein motifs in the rib formation-blocking function of these proteins. We have found a 7 aminoacid motif located just upstream of the homeodomain, which is specific to Hox10 proteins. This motif is essential for Hox10 function but it is not sufficient to provide full rib inhibiting properties to other Hox proteins. The full activity of this motif requires interaction with Hox10 sequences N-terminal to it, which remain to be identified. Further analyses revealed that a threonine present in the Hox10- specific motif is central to its activity. Finally, analyses of Hox 10 proteins by 2D gel electrophoresis revealed a complex pattern of post-translational modifications in the Hoxa10 protein that are required for its full function.
ACTION SELECTION AND ACTION TIMING IN THE PREMOTOR CORTEX Our aims are to understand:
We documented neural correlates of action timing in the preomotor cortex, documenting two classes of waiting-time predictive neurons. We also began developing a task in which we can manipulate the availability of potential action options.
Our group is interested in several aspects of vertebrate embryonic development. The ultimate goal of our research is to understand the molecular mechanisms that translate patterning information into morphogenetic processes during formation of the vertebrate embryo. For a number of years, we have explored different developmental processes, including the ear formation, the neural crest induction/migration and differentiation of branchial arches. Our most recent work is focused on the development and evolution of the vertebrate axial skeleton, mostly focused on the role that Hox genes play in these processes. We are particularly interested in understanding the molecular mechanisms that mediate Hox activity, with special focus on the functional interactions between Hox genes and the chromatin.
Experimental setup of a rat performing an olfactory categorisation task, used to investigate the computation of decision uncertainty through inactivation and electrophysiological recordings on the olfactory system.
A custom fiberoptic light detection system developed in the group, which will be used to measure fluorescence changes in freely moving rats and mice.
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MECHANISMS COORDINATING GASTRULATION AND AXIAL ELONGATION WITH PATTERNING IN VERTEBRATES We want to establish what determines the transition from the production of the different mesodermal sections and how they relate to the induction of patterning genes along the rostro-caudal axis. Using in situ hybridisation techniques, we have observed that variations in the expression of the gene Snail1 marks the transition from the body to the tail in the gastrulating mouse embryo. This, combined with published genetic data, suggested that this gene might have a central role in the production of lateral mesoderm corresponding to the limb and interlimb areas. To explore this, we have produced transgenic lines expressing a tamoxifen-regulated version of cre (cre-ERT) in the primitive streak. We have already tested and characterised these mice using the reporter strain ROSA26-YFP. These mice will be used, in combination with those carrying a floxed allele of Snail1 to inactivate this gene at different developmental time points. With this approach we want to bypass the lethal effects of the snail mutation at early developmental stages and evaluate the role of this gene later in gastrulation and in patterning the vertebrate skeleton.
IGC ANNUAL REPORT ‘10
RESEARCH GROUPS
OPPOSITE EFFECTS OF HOX6 AND HOX10 GENES IN PATTERNING THE AXIAL SKELETON. Left - Hoxb6 induces rib formation throughout the whole skeleton when precociously expressed in the presomitic mesoderm. Right Conversely, under the same experimental conditions Hoxa10 completely blocks rib formation.
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EARLY FLY DEVELOPMENT
DEVELOPMENT, EVOLUTION AND THE ENVIRONMENT
Head: Rui Gonçalo Martinho
Head: Christen Mirth
PhD in Biology University of Sussex, UK
PhD in Zoology University of Cambridge external website: http://web.me.com/christenmirth/lab_page/Welcome.html THIS GROUP WAS ESTABLISHED AT THE IGC IN JUNE 2010
Our main research interests relate to mitosis, cell proliferation, and tissue morphogenesis. More specifically, we are taking advantage of Drosophila melanogaster as a model system to better define the molecular mechanisms responsible for the correct orientation of the mitotic spindle during symmetric mitosis of epithelial cells. We want to understand the differential requirements of protein N-terminal acetylation in somatic and germ-line stem cells during mitosis, and explain why a known human tumor suppressor gene is specifically important for the onset of zygotic expression and tissue morphogenesis in the earliest stages of Drosophila development. ANALYSIS OF EARLY TRANSCRIPTIONAL ACTIVATION AND GERM-LINE SEGREGATION IN Drosophila melanogaster The aim of this project is to study the development of the germ-line in the Drosophila embryo. We identified PKCa as being required for mitotic spindle orientation and cell shape during symmetric mitosis of epithelial cells. We also identified and characterised a novel N-terminal acetylatransferase related to San, which is required for mitosis and is likely to explain the differential requirements of San within the female germ-line stem cells.
GROUP MEMBERS Leonardo Gaston Guilgur (Post-doc) Denisa Liszekova (Post-doc) Ana Rita Pimenta Marques (PhD Student) Tânia Ferreira (PhD Student) Pedro Prudêncio (Lab manager) COLLABORATIONS Thomas Arnesen (Unversity of Bergen, Norway) Kris Gevaert (University of Gent, Belgium) Buzz Baum (University College of London, UK) Jordi Casanova (University of Barcelona, Spain) Florence Janody, Jorg Becker (Instituto Gulbenkian de Ciência, Portugal) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal
Our lab studies the regulation and evolution of environmentally-dependent traits in species from the genus Drosophila. Recently, our efforts have focused on two traits that depend on nutritional cues: 1. Body size; 2. Larval foraging behaviour.
COLLABORATIONS Alexandre Shingleton (Michigan State University)
We use the genetic tools available in Drosophila melanogaster to dissect how environmental signals, like nutrition, regulate larval growth and foraging choices. By analysing the changes in these mechanisms across species, we hope to identify how these environmentally-dependent traits evolve to create species-specific differences in foraging behaviour and adult body size.
THE EVOLUTION OF FORAGING STRATEGIES IN THE GENUS DROSOPHILA With the ultimate goal of identifying genomic sites responsible for the evolution of foraging strategies, we will survey the range of larval foraging strategies used by larvae from the genus Drosophila, and determine how differences in foraging strategies evolve. To address this question, we will explore the evolution of different burrowing frequencies between D. ananassae and D. pallidosa. Over the past year, we have identified several differences in larval foraging and dispersal behaviour between species of Drosophila. Across species groups, larvae differ in their tendency to associate with one another when burrowing, their burrowing rate and their use of preexisting hole in the media. For some traits, like degree of association when burrowing, differences across species groups are significantly larger than within the group. Burrowing rate and use of pre-made holes, on the other hand, differ significantly both within and across species groups. In addition, we have identified novel behaviours, such as jumping and a range of aggressive and aversive behaviours. The frequency at which larvae perform these behaviours also differs between species. Our species survey, outlined above, has uncovered several closely related species that show significant divergence in their foraging behaviour. Of particular interest, four species closely related to D. ananassae burrow at low frequencies and perform extended search. We have explored how varying environmental parameters affects burrowing frequency. Changes in burrowing rates can be caused by light, food quality, larval density and substrate hardness. Furthermore, species within this group show differing preferences for each of these parameters.
IGC ANNUAL REPORT ‘10
FUNDING Instituto Gulbenkian de Ciência (IGC), Portugal
NUTRITION-DEPENDENT REGULATION OF BODY SIZE IN Drosophila melanogaster This project aims to investigate how insulin and ecdysone signalling interact to regulate body size. In particular, we are examining the role of direct interactions between FoxO and the ecdysone receptor. A second aim is to determine the role of ecdysone signalling on the growth and differentiation of the developing adult tissues. The functional ecdysone receptor is a heterodimer of Ecdysone Receptor (EcR) and ultraspiracle (Usp). Our studies show that FoxO binds to Usp, but not to EcR. Furthermore, we have found that knocking down FoxO in the PG causes premature differentiation of the imaginal discs, suggesting that it plays a role in regulating ecdysone production. We have narrowed down the FoxO-Usp binding region to a 30 amino acid domain in the FoxO protein. In the future, we will identify the function of these FoxOUsp complexes. If we specifically ablate the PG, we find that the imaginal discs grow at greatly reduced rates. Furthermore, ecdysone signalling promotes nutrition-independent differentiation of discs in post-critical weight larvae. We are currently working to identify the pathways regulated by ecdysone. To begin, we are constructing a patterning map that explores the expression of patterning gene products throughout the third instar. We will use this map to identify the components of patterning pathways that change during the critical weight transitions and thus are likely activated by ecdysone.
CHARACTERISATION OF THE TRANSCRIPTIONAL ACTIVATION OF THE QUIESCENT ZYGOTIC GENOME AFTER OOCYTE FERTILISATION In order to study early transcriptional regulation in the Drosophila embryo., we found that complementation group 7 was defective for early zygotic expression and blastoderm cellularisation. We named this mutant fandango based on its blastoderm cellularisation phenotype. We identified the affected gene and we are currently defining the function of the encoded protein during transcriptional activation of the quiescence zygotic genome. Our data suggests that during early embryonic development there are particular contraints to pre-mRNA splicing.
RESEARCH GROUPS
GROUP MEMBERS Takashi Koyama (Post-doc) Marisa Oliveira (PhD Student) Sara Lennox (Research Technician) Fiona Kettner (Trainee)
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INVESTIGATING INTERACTIONS BETWEEN FORKHEAD BOX O (FoxO) AND ULTRASPIRACLE (Usp) IN THE REGULATION OF BODY SIZE AND DEVELOPMENTAL TIMING IN DROSOPHILA MELANOGASTER. The expression of Foxo (A and C) and Usp (B and D) in salivary glands and fat body from starved (A-B) and fed (C-D) third instar larvae.
BURROWING RATE IN SPECIES OF THE MELANOGASTER SPECIES GROUP. Asterisks indicate significant differences determined by a Wilcoxon Non-Parametric Test (p>0.0001). The tree below the graph indicates relationships between species. Error bars are 1 standard error of the mean. prost: Drosophila prostipennis; lutes: D. lutescens; takah: D. takahoshii; melan: D. melanogaster; simul: S. simulans; mauri: D. mauritania; santo: D. santomea; yakuba: D. yakuba; erecta: D. erecta; palli: D. pallidosa; anana: D. ananassae; bipec: D. bipectinata; parab: D. parabipectinata; maler: D. malerkotliana.
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BEHAVIOURAL NEUROSCIENCE
ANIMAL BEHAVIOUR
Head: Marta Moita
Head: Rui Oliveira
PhD in Neuroscience Universidade do Porto, Portugal
PhD in Biology University of Lisbon, Portugal external website: http://www.ispa.pt/ui/uie/ibbg/
THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
We are interested in understanding the neural mechanisms underlying behavioural plasticity using a combination of behavioural, pharmacological, molecular and electrophysiological tools. In particular, we are studying how prior experience and how social interactions shape behaviour. To this end, we are studying fear; both how animals learn to fear cues that are predictive of aversive events or threats, and how fear can be socially transmitted, i.e. how animal respond to the distress of con-specifics. We chose fear learning since it is conserved across species, entailing fast robust learning and very long lasting memories. We are also studying decision-making in the context of social interactions, using game theory to test how rats learn and evaluate the payoffs that result from the interaction with another individual. NEURAL MECHANISMS OF TRACE AUDITORY FEAR CONDITIONING Although it has been assumed that trace fear conditioning relies on activity in the amygdala, due to its well established role in delayed fear conditioning (where tone and shock overlap in time), the role of the amygdala in trace fear conditioning remained elusive. We temporarily inactivated the amygdala and found this structure to be crucially implicated in trace fear conditioing regardless of the length of the interval between tone and shock.
GROUP MEMBERS Kensaku Nomoto (Post-doc) Marta Guimarãis (PhD student) Raquel Antunes(PhD student) Ana Pereira (PhD student) Scott Rennie (PhD student) Ana Gregório (Research Technician) COLLABORATIONS Hugh Blair (University of California Los Angeles -UCLA, USA) Susana Lima (Champalimaud Neuroscience Programme at the IGC, Portugal) Glenn Schafe (Yale University, USA) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal Champalimaud Foundation, Portugal
The main research aim of our group is the understanding of the interrelationship between neuroendocrine mechanisms and social behaviour, using an integrative approach (i.e. by integrating ecological/evolutionary analysis with physiological analysis of behaviour). With our studies we hope to contribute to the understanding of how complex social environmental processes interact with biological systems. We have been developing two main research lines: 1. To understand how the social environment modulates hormones and gene expression in order to affect the expression of subsequent behaviours; 2. The study of the neuroendocrine mechanisms underlying behavioural plasticity. Both research lines have been mainly focused in teleost fish as study models (tilapia, pecock blenny and zebrafish) but we have also expanded our research to other vertebrate groups, including humans. In these research lines we combine neuroendocrinology and molecular biology techniques with behavioural observations and we conduct studies both in the lab and in freeliving subjects. WINNERS AND LOSERS: SOCIAL MODULATION OF HORMONES, BRAIN AND BEHAVIOUR In 2010 we completed the description of adult neurogenesis in tilapia including the characterisation of proliferation, migration and differentiation of newborn cells, and we started the behavioural experiments both with tilapia and with zebrafish on social regulation of adult neurogenesis. In both species we have also investigated how social information is translated into neuroendocrine signals. Results indicate that cognitive appraisal of social interactions and social context is needed in order to trigger a biological response. Two fish model species are used: zebrafish (Danio rerio) and the Mozambique tilapia (Oreochromis mossambicus), to investigate how social interactions influence brain function (i.e. patterns of gene expression in areas of interest in the brain using qPCR and gene microarrays, and adult neurogenesis), and how socially driven hormonal changes influence subsequent behaviour.
COOPERATION IN SOCIAL DILEMMAS IN RATS Game theory has constituted a powerful tool in the study of the mechanisms of reciprocity. Having shown that, in a Prisoner’s Dilemma game, rats shape their behaviour according to the opponent’s strategy and the relative size of the payoff resulting from cooperative or defective moves, we now aim at dissecting the mechanisms. We have optimised a protocol for training rats in a new automated maze designed to study the behaviour of rats in different social dilemma games. We have tested the rats' ability to discriminate between different amounts of food pellets that will be used in the payoff matrix of different games. NEURAL MECHANISMS OF OF SOCIAL TRANSMISSION OF FEAR IN RATS This project aims at investigating the mechanisms underlying social transmission of fear (STF) in rats, i.e. how rats respond to the fear displayed by a con-specific. In order to unravel the neural circuit underlying STF, we will first determine how prior self-experience with shock contributes to STF and what are the sensory cues that mediate this process. We have developed a paradigm for studying social transmission of fear in rats. We have found that fear displayed by a demonstrator rat, triggered by a tone to which this rat has been conditioned, will lead to freezing in an observer rat, provided the observer had prior experience with footshock. In addition we have found that STF does not require visual input or contact between the two rats. Finally, we found that alarm calls are neither sufficient nor necessary for STF.
IGC ANNUAL REPORT ‘10
COLLABORATIONS Gunther Zupanc (Northeastern University, USA) Hans Hofmann (University of Texas at Austin, USA) Ewa Kulczykowska (Oceanology Institute of the Polish Academy of Sciences, Poland) Svante Winberg (Uppsala University, Sweden) Adelino Canário (Universidade do Algarve, Portugal) Mike Orger (Champalimaud Foundation, Portugal) Annemie van der Linden (Antwerp University, Belgium) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal
Markov chain analysis of behavioural transition matrix of zebrafish fights unravels a temporal structure in zebrafish aggressive behaviour which makes it prone for the investigation of underlying proximate mechanisms.
NEUROENDOCRINE CONTROL OF REPRODUCTIVE BEHAVIOUR IN THE MOZAMBIQUE TILAPIA: MECHANISMS AND EFFECTS OF THE SOCIAL ENVIRONMENT In 2010 we concentrated on developing probes for and optimising in situ hybridisation of immediate early genes and on running three types of behavioural assays: 1. Establishment of stable vs. unstable dominance hierarchies to assess neuroendocrine correlates of social status and how status reversals impact on them; 2. Mirror elicited fights to address how social information is translated into neuroendocrine signals; 3. Olfactory stimulation assays using social pheromones that signal social status. HPLC analysis of AVT and isotocin levels in stable social groups indicate that subordinate males have higher levels of vasotocin in the olfactory bulbs and the pituitary gland than dominants, suggesting a modulaton of chemical comunication by vasotocin in this species (vasotocin is an anti-diuretic hormone and urine is stored in dominants, but not in subordinates, to be actively released during social interactions). Quantitative PCR of immediate early genes in microdissected brain areas indicates differential brain activation profiles elicited by different odorant stimuli. The aim of this project is to investigate the neuroendocrine mechanisms involved in the control of social (territorial and courting) behaviour in the Mozambique tilapia. Using the expression of immediate early genes (egr-1, c-fos) we aim to map the patterns of brain activation associated with the expression of different types of social behaviour. We also aim to assess the effects of sex steroids (androgens in particular) and neuropeptides (vasotocin and isotocin) in the modulation of social behaviours.
RESEARCH GROUPS
GROUP MEMBERS João Marques (PhD Student) Rodrigo Abril Abreu (PhD Student) José Miguel Simões (PhD Student) Magda Teles (PhD Student) Ana Catarina Oliveira (Research Technician)
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SOCIAL REGULATION OF BRAIN TRANSCRIPTOME IN ZEBRAFISH. Type of social experience (isolation, winning, losing or fighting an unsolved fight against its own image in a mirror) regulates the profile of gene expression in the brain.
STUDY OF SOCIALLY DRIVEN CHANGES IN GENE EXPRESSION IN THE CICHLID FISH BRAIN. A - Lateral view and sagittal section of cichlid fish brain. B - Coronal section showing areas of interest in the brain that are involved in the processing of social signals. C - Development of a social task with controlled presentation of chemical and visual signals.
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INFECTION AND IMMUNITY
DISEASE GENETICS
Head: Michael Parkhouse
Head: Carlos Penha Gonçalves
PhD in Biochemistry University of London, UK
PhD in Immunology Umea University, Sweden
The theme of the group is the reciprocal adaptation between an infectious organism and its host. The necessity to recognise and destroy invading pathogens has played a crucial role in the evolution of the immune system of both vertebrates and invertebrates. At the same time, pathogens, in particular viruses, have evolved reciprocal strategies to manipulate the immune system. As there are a range of pathogen life styles, an efficient immune system must select the immune effector mechanism most appropriate to the biology of the pathogen. Equally important, the immune response, once selected, must be terminated. Failure to switch off both appropriate and inappropriate immune response is the cause of many un-infectious diseases, such as autoimmunity and inflammation. Thus the study of how pathogens control immune responses will offer novel approaches for the manipulation of the immune responses in health and disease, with novel vaccines and strategies to downregulate the immune system (e.g. inflammation) being the most obvious possibilities. Therefore, we are identifying and characterising virus host evasion genes directed towards subversion of cell biology and innate immunity. The two viruses that we have selected are Herpesvirus and the African Swine Fever Virus. There is a small, but socially relevant project, focusing on control, through diagnosis and vaccine development, of the human tapeworm parasite.
GROUP MEMBERS Sílvia Correia (Post-doc) Rute Nascimento(Post-doc) Sónia Ventura (PhD student) Helena Costa (PhD student) Emanuel Costa (Research Techician) COLLABORATIONS Sun Huaichang (College of Veterinary Medicine, Yangzhou University, China) Alexandre Leitão (Faculdade de Medicina Veterinária, Univ.Técnica de Lisboa Portugal) John Sinclair (University of Cambridge, UK) Steve Goodbourn (St. George's Hospital, University of London, UK) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal Framework Programme 7 (FP7), European Commission
GROUP MEMBERS Maria de Jesus Trovoada (Post-doc) Luciana Moraes (Post-doc) Nadia Duarte (Post-doc) Ligia Deus (PhD student) Joana Rodo (PhD student) Joana Corte-Real (PhD student) Lurdes Duarte (PhD student) Liz Ball (PhD student) Francsico Freixo (Graduate Student - Optimus Alive Fellow) COLLABORATIONS Lars Hviid, Dan Holmberg (University of Copenhagen, Denmark) Chris Jansen (Leiden University Medical Center, The Netherlands) Claúdio Marinho (Universidade de São Paulo, Brazil) Maria Mota (Instituto de Medicina Molecular, Portugal) Jon Clardy (Harvard Medical School, USA) Peter Crompton (National Institutes of Health, USA) Taane Clark (London School of Hygiene and Tropical Medicine, UK) Rosário Sambo (Hospital Pediátrico de Luanda, Angola) Linda Wicker (University of Cambridge, UK) Kristina Lejon ( University of Umea, Sweden) FUNDING Fundação para a Ciência e Tecnologia (FCT), Portugal Fundação Luso-Americana para o Desenvolvimento (FLAD), Portugal
PREGNANCY-ASSOCIATED MALARIA The main aims of this research are to investigate the mechanisms of placenta malaria pathogenesis with a focus on the in vivo the adhesion of the parasite to the placental tissue and the role of innate immunity molecular and cellular components provided by the fetal tissues. We have developed in vivo imaging of placental malaria infection, and characterised preganancy-associated P. Berghei isolates. PLASMODIUM DEVELOPMENT IN HEPATOCYTES We aim to identify key hepatocyte pathways and molecules that are targeted by the parasite liver stages, at the level of the individual infected hepatocytes. We have obtained evidence that Belr1 excerts its effect at the level of the non-parenquimal liver cells.
MECHANISM OF CELL CYCLE ARREST INDUCED BY A HOST MODIFICATION GENE OF THE HUMAN BETA HERPESVIRUS HCMV This application will define the mechanism of the conserved, “non-assigned”, non-homologous UL76 gene of HCMV, which we have shown to induce host cell cycle arrest and apoptosis, and which is therefore likely to play a critical role in the pathogenesis of herpesvirus infections. In conclusion of this project we constructed the UL76 mutant HCMV and compared with the wild type virus and a mutant virus. A 50-fold reduction on viral production of mutant virus compared to wild type viruses was observed, but there was no difference in the cell cycle arrest. Although we have demonstrated that UL76 HCMV gene induces cell cycle arrest it is not responsible for the cell cycle arrest observed in viral infection. Funded by FCT.
MALARIA IMMUNOGENETICS This project has two main aims: to identify genetic and antigenic determinants of cerebral malaria pathogenesis and to follow the natural decay of immunological memory to the malaria parasite in a previously exposed population. We have identified HMOX1 and TGFB2 genes as risk factors for cerebral malaria in Angolan children. B1 CELLS AND NATURAL ANTIBODIES IN TYPE 1 DIABETES (T1D) PATHOGENESIS We aim to correlate alterations in the development and functional activation of autoreactive B1 cells with T1D pathogenesis and to identify genetic determinant auto-antibodies in the autoimmune attack on pancreatic Beta-cells. We have identified abnormal phenotypes in B1 cells of the NOD mouse and found genetic assocations of human T1D and mutiple autoreactivity to the IgH locus.
INHIBITION TO INTERFERON RESPONSE BY THE AFRICAN SWINE FLU VIRUS Our objective is to determine the mechanisms and consequences of three non-homologous host evasion genes (I329L, K205R and A276R) of the economically important, frequently fatal African Swine Fever Virus (ASFV). All 3 genes inhibit a major component of innate immunity, the Interferon (IFN) response, and may have practical application through the development of novel pharmaceuticals manipulating IFN responses and through the construction of an attenuated gene deletion ASFV vaccine. Our results have already identified the I329L gene as an inhibitor of the TLR3 signalling pathway and TRIF was suggested to be its intracellular target. Funded by FCT.
IGC ANNUAL REPORT ‘10
Based on data generated in our lab in coming years a strong theme in the lab will be to investigate particular cell types of the innate immune system and to decipher their role: 1. In mediating pathogen-induced pathology (in pregnancy and cerebral malaria); 2. In conferring infection resistance (in malaria liver stage); 3. In shaping the responsiveness to auto-antigens (in T1D).
EVALUATING AND CONTROLLING THE RISK OF AFRICAN SWINE FEVER (ASF) IN THE EU The aim is to provide new tools and strategies for the control of ASF in Africa and reduce the risk of importation and/or spread of the disease in EU member states. Four proteins (B602L, p54, A104R and K205R) were identified as potential target antigens in sensitivity and specificity tests. These recombinant proteins were produced and have been used as antigens to test field ASFV isolates in new recombinant ELISAs. As the K205R protein revealed high IgM titres, it has been produced, to develop a new commercial kit able to detect recently ASFV infected animals. An additional ASFV Interferon evasion gene has been identified using luciferase reporter assays, and the mechanisms being used by this viral gene in the manipulation of both Interferon induction and interferon response through the receptors is being investigated. Funded by EU.
RESEARCH GROUPS
The lab started by adopting forward genetics approaches to identifying genetic factors related to disease both in mice and humans. Two diseases are the focus of our work: Malaria and Type 1 diabetes (T1D). We aim to investigate the pathogenesis of these diseases by combining cell and molecular biology methodologies with classical genetics techniques. A good part of our research is converging on searching for correlations of the response to different innate immune system stimuli (e.g TLR signals) and specific outcomes of the immediate inflammatory reaction as well as the adaptive response. The emerging picture is that specific cell types that are located in defined sites in the body (e.g. placental macrophages, peritoneal B cells) respond to innate stimuli and condition the adaptive immune system response in a PAMPspecific fashion. This is leading us to see such innate responses as promising targets to deviate the immune response and halt disease progression.
Informing and engaging local populations on the African island of Principe in the project on malaria immunogenetics.
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COMPUTATIONAL GENOMICS
BEHAVIOUR AND METABOLISM
Head: José Pereira Leal
Head: Carlos Ribeiro
PhD in Biomedical Sciences Universidade do Porto, Portugal external website: http://www.evocell.org/Welcome.html
PhD in Cell Biology University of Basel, Switzerland
We are interested in the evolutionary mechanisms underlying the origins and evolution of cellular life and the complex structures within the cell, the transitions to multi-cellularity, and the medical applications of evolutionary genomics. Our research encompasses themes that are broadly classified as evolutionary cell biology, systems biology, pathogenomics, and translational or medical bioinformatics. EVOLUTIONARY CELL BIOLOGY The aims of this project are to study the origins of cellular structures, and to develop the methods and resources that enable evolutionary studies in cell biology. Towards this end, we developed three data integration platforms: TrafficDB, CentrioleDB and SporeDB, where automated methods for sequence classification are integrated with morphological information, described by image data and novel controlled vocabularies. In collaboration with the Cell Cycle Regulation laboratory we characterised the evolutionary pathway of the centriolar duplication machinery using both computational and experimental approaches (published). We have also discovered that there is a selective loss of genetic redundancy when bacteria adopt an obligate intracellular lifestyle, such as chloroplasts and mitochondria (accepted for publication).
THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
GROUP MEMBERS Pedro Coelho (Post-doc) Luisa Rodrigues (Post-doc) Yoan Diekmman (PhD student) Sofia Braga (PhD student) Marc Gouw (Research Student; left September 2010) COLLABORATIONS Monica Bettencourt-Dias, Miguel Seabra (Instituto Gulbenkian de Ciência, Portugal) Juliette Azimzadeth (University of California San Francisco, USA) Keith Gull (Oxford University, UK) Adriano Henriques (Instituto de Tecnologia Química e Biológica, Portugal) Carlos Caldas (Cambridge University, UK) José Luis Passos Coelho, Paula Chaves (Instituto Português de Oncologia, Portugal) David Pellman, Max Loda (Harvard Medical School, USA) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal
CELL BIOLOGY OF CANCER We aim to understand the molecular basis of tumor heterogeneity and cancer progression. We are studying the molecular and clinical heterogeneity of breast cancer, and our preliminary results suggest two distinct entities, driven by different molecules and processes and with distinct outcomes. Using gene expression data we have identified novel prognostic markers for breast cancer. We are currently collaborating with pathologists at Portuguese hospitals to test our computational predictions by immunohistochemistry in human samples.
We are interested in understanding how molecular and cellular mechanisms control complex biological processes at the level of the whole organism. For this we are focusing on how the internal metabolic state of the fruit fly Drosophila melanogaster affects its behavioural decisions. Starting from novel behavioural paradigms we use molecular genetic techniques to identify and characterise genes and neuronal populations involved in producing the appropriate behavioural response to a specific metabolic need of the fly. MOLECULAR MECHANISMS OF NUTRIENT CHOICE We want to understand how Drosophila knows what type of nutrients it needs and which are the molecular mechanisms used by the nervous system to change the behaviour of the animal to allow it to find and eat the required nutrients. Last year we showed that mating status is a critical modulator of nutritional decision-making in females, and that it relies on the action of the sex peptide receptor (SPR) in ppk+ sensory neurons. Neuronal TOR/ S6K function is another critical input to this decision, possibly signalling the fly’s current nutritional status. We are now looking into how this conserved pathway acts in the nervous system to control feeding. Furthermore we have continued to analyse genes identified as being required for nutrient choice in a neuronal whole-genome RNAi screen. Taken together these studies will provide a model and an entry point for studying nutrient balancing and value-based decision making at the molecular level. NEURONAL MECHANISMS OF NUTRIENT CHOICE We want to identify and analyse the neuronal networks used by Drosophila to change the behaviour of the animal to allow it to find and eat the required nutrients. We have used genetic approaches to identify neuronal populations which are required for nutrient choices. Currently we are analysing the identified neuronal substrates for nutrient homeostasis to understand how these neuronal populations act to guide feeding decisions.
GROUP MEMBERS Teresa Montez (Post-doc) Laura Napal Belmonte (Post-doc) Samantha Herbert (Graduate student) Ana Paula Elias (Lab Manager and Research Technician) Ana Carolina Doran (Research Technician) Célia Modesto Baltazar (Research Technician) COLLABORATIONS Aldo Faisal (Imperial College London, UK) FUNDING Champalimaud Foundation, Portugal
What type of food should the animal choose?
QUANTITATIVE ANALYSIS OF FEEDING BEHAVIOUR IN DROSOPHILA In collaboration with the laboratory of Aldo Faisal at Imperial College London we have developed a prototype setup which will allow us to use automated video analysis to quantitatively link genetics to feeding behaviour in the fruit fly, the main aim of this project.
Drosophila adult brain (gold) with specific neuronal subsets marked by GFP (green).
Automatically tracked path of a foraging fly.
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COMPLEX ADAPTIVE SYSTEMS AND COMPUTATIONAL BIOLOGY Head: Luis Rocha
STOCHASTIC MODELS OF TOPOLOGY CONSTRAINTS ON COMPLEX NETWORKS The aim is to study the transitive properties of complex networks modeled as weighted graphs: studying the impact of alternative distance measures on scale free and small-world behaviour, and developing stochastic models of vertex aging in networks, to better predict network growth. Ongoing analysis of large-scale wikipedia data. A dissertation based on this project and two papers are to be submitted.
PhD in Systems Science State University of New York, USA external website: http://cnets.indiana.edu/groups/casci
We are interested in the informational properties of natural and artificial systems which enable them to adapt and evolve. This means both producing computational models of biological systems to understand the evolutionary role of information, as well as abstracting principles from biology to produce adaptive information technology. Our current research projects are on complex dynamics in biological networks (gene regulation, cell signaling, and metabolic networks), text and literature mining (in proteomics, proteinprotein interaction and pharmacokinetics), computational models of RNA Editing, artificial immune systems, genomic multivariate analysis, evolutionary systems, artificial life, cognitive science, and biosemiotics. BIOMEDICAL LITERATURE MINING The aims are to establish literature-based automatic discovery, classification and annotation of protein-protein and gene-disease interactions, pharmokinetic data, protein sequence family and structure prediction, functional annotation of trancription data, enzyme annotation publications, etc. During 2010 a number of papers were accepted for publication in various conferences and journals. One of these papers was awarded the "Best paper" price at 9th the International Conference on Artificial Immune Systems (ICARIS 2010), Edinburgh, U.K.. We are currently testing and extending our classification engines using symbolic regression.
GROUP MEMBERS Manuel Marques-Pita (Post-doc) Michael Conover (PhD Student) Alaa Abi-Haidar (PhD Student) Tiago Simas (PhD Student) Azadeh Nematzadeh (PhD Student) Artemy Kolchinsky (PhD Student) COLLABORATIONS Anália Lourenço, Miguel Rocha (Universidade do Minho, Portugal) Hagit Shatkay (Queen's University, Canada) Marta Cascante (University of Barcelona, Spain) Jim Crutchfield (University of California, Davis, USA) Santiago Schnell (Michigan University, USA) George Kampis (Northwestern University, USA) Luis Amaral (Univeraity of Budapest, Bulgaria) FilipaAlves,AlekosAthanasiadis,JorgeCarneiro(InstitutoGulbenkian de Ciência, Portugal) Stefan Mass (Lehigh Univeraity, USA) Pedro Lima Porfirio Silva (Instituto Superior Técnico, Portugal) Nuno Crato (Instituto Superior de Economia e Gestão, Portugal) FUNDING FLAD Computational Biology Collaboratorium, Portugal Fundação para a Ciência e a Tecnologia (FCT), Portugal Uninova, Portugal
COLLECTIVE DYNAMICS IN COMPLEX BIOCHEMICAL NETWORKS This project entails modeling of the dynamics of complex biochemical networks, to identify control, modularity, robustness and collective computation. Currently working with models of genetic regulation in yeast, body segmentation in Drosophila, intracellular signal transduction in fibroblasts, a genome-scale transcriptional and metabolic network for E-Coli, and others. In 2010 our research group obtained one of the highly competitive research and development grants from the Fundação para a Ciência e a Tecnologia to continue our work on the characterisation of control, modularity and collective computation in discrete models biochemical networks. We also have a paper accepted for a very large conference organised by the IEEE. Finally, during 2010 we consolidated our collaboration with Minho University on the analysis of very large models of regulation and metabolism in E. Coli. We are currently in the process of preparing our results for publication for this collaboration, as well as for other models that were analysed in 2010. COMPUTATIONAL MODELS OF RNA EDITING We are developing computational models to study the evolutionary implications of genotype editing in the living organisation. Our goal is twofold: (1) to study the role of RNA Editing regulation in the evolutionary process, and (2) to investigate the conditions under which genotype edition improves the optimisation performance of evolutionary algorithms. Based ony new codewe conducted expansive simulations. Continued collaborations with Alekos Athanasiadis (IGC) and Stefan Mas (Lehigh) to make simulations results more applicable to realistic scenarios. We have two papers in preparation. ARTIFICIAL MODELS OF T-CELL CROSS-REGULATION We use Carneiro's Model of Cross-regulation in T-Cell dynamics to produce bio-inspired algorithms for binary classification. The goal is to gain further insights about T-Cell cross-regulation in the vertebrate immune system, and produce useful bio-inspired algorithms for text mining and spam detection. We published new simulations to ascertain the dependence of the model to the presentation sequence of self and nonself antigens, the effect of rates of appoptosis, and dependence on initial conditions. Three papers were published, one of which received the best paper award for the leading conference on Artificial Immune Systems. We are also integrating this research in a wider research project on "Institutional Robotics" with Pedro Lima and Jorge Carneiro.
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Decision surfaces on the protein-protein interaction article test data of Biocreative III, as produced by our Variable Trigonometric Threshold model, Lourenco, A et al. (2011). Blue (red) data points represent PubMed documents relevant (irrelevant) for protein-protein interaction.
Pathway modules in the Canalising Dynamics of the Drosophila Segment Polarity Network automata network model.
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MEMBRANE TRAFFIC IN DISEASE AND NOVEL THERAPIES
INFLAMMATION
Head: Miguel Seabra
Head: Miguel Soares
PhD in Biochemistry and Molecular Biology University of Texas, USA external site: http://www.cedoc.org/PDF/CEDOC_Seabra.pdf
PhD in Science University of Louvain, Belgium
THIS GROUP IS A MEMBER OF CEDOC-CENTRE FOR CHRONIC DISEASES
One of the most important challenges for the Biomedical Sciences this century is to develop a comprehensive knowledge of the fundamental unit of life, the cell. One main question in Molecular Cell Biology is focused on understanding how cells achieve their highly sophisticated internal compartmentalisation. Each organelle is individualised by membranes, which contain specific proteins and lipids to execute specific functions. How are proteins and lipids sorted and retained to different locations or in other words how are organelles made, maintained (identified) and how do they communicate with each other? Our work in the last 15 years has dealt with this problem and our approach has been to study both normal cells and disease processes. We are currently working in a variety of diseases with different phenotypes whose common feature is dysfunction of intracellular membrane trafficking pathways. We also wish to apply the fundamental knowledge to develop new therapeutic approaches to these diseases. MOLECULAR MECHANISMS OF PARASITOPHORUS VACULE FORMATION IN MALARIA INFECTION The aim of this project is to carry out a comprehensive study of the localisation of all the Rab proteins during Plasmodium infection in liver cells. There seems to be some association between certain specific host Rabs and the parasite, such as Rab3b, Rab3d, Rab6a, Rab8a, Rab9a, Rab 15 and Rab11b, which have all in some way been descrived as golgi or/and secretory Rabs.
GROUP MEMBERS José Ramalho (Visiting Scientist) Teresa Barona (Visiting Scientist) Ana Sofia Tavares (Visiting Scientist) Abul Tarafder (Post-doc) Elsa Seixas (Post-doc) Francisco Pereira (Post-doc) Laura Santos (Post-doc) Carolina Matos (PhD Student) Cristiana Pires (PhD Student) Inês Rodrigues (PhD Student) Lucio Iannone (PhD Student) Mafalda Silva (PhD Student) Maria Correia (PhD Student) Margarida Silva (Trainee) Marta Pedro (Trainee) Inês Gato (Trainee)
Inflammation is an immediate response to foreign challenge and/or tissue injury characterised by local and transient extravasation of soluble molecules and leukocytes from blood into non lymphoid tissues. While the physiological purpose of inflammation is to restore homeostasis there are many instances where inflammation becomes pathological. Moreover, there is a general consensus that some of the major causes of human morbidity and mortality are in fact due to pathological conditions in which inflammation and/or immunity are the underlying cause of disease. The research effort developed in our laboratory is aimed at understanding the cellular and molecular mechanisms assuring that in the overwhelming majority of cases inflammation exerts its physiologic purpose without becoming pathological. Our body of work supports the notion that one of such mechanisms relies on the expression of cytoprotective genes that allow inflammation to progress without causing irreversible tissue damage.
COLLABORATIONS Tanya Tolmachova, Robert Sinden, Alistair Hume (Imperial College London, UK) Sebastien Amigorena, Graça Raposo (Institut Curie, France) Clare Futter (Institute of Ophtalmology, UK) Maria Mota (Instituto de Medicina Molecular, Portugal)
MODULATION OF PROGRAMMED CELL DEATH BY FREE HEME Under this project we aim to understand the molecular basis underlying the cytotoxic effects of free heme. In our laboratory we have shown that the cytotoxic effect of free heme plays an important role in the pathogenesis of a variety of inflammatory diseases, namely severe forms of cerebral malaria, in which hemoproteins release their prosthetic heme groups.
FUNDING Fundação para a Ciência e Tecnologia (FCT), Portugal
MECHANISMS OF HOST TOLERANCE TO INFECTION The goal of this project is to understand the molecular basis underlying host tolerance to infection. We are exploring the hypothesis that several genes that regulate the deleterious effects of free heme might control host tolerance to infection. Our data suggests that this is indeed the case for both Plasmodium and polymicrobial infections. Our latest findings establish that Hemoxygenase-1 (HO-1) limits the cytotoxic effects of free heme produced during microbial infections, thus suppressing the onset of severe sepsis irrespectively of pathogen load.
MOLECULAR MECHANISMS OF ORGANELLE MOTILITY This project aims to study the role of the Rab27/Mlph/MyoVa complex in melanosome trafficking and the role of the Mypt phosphatase in this process. We proposed that Mlph is targeted to and/or stabilised on melanosomes by Rab27a, and then recruits MyoVa, which provides additional stability to the complex and allows melanosomes to transfer from MT to actin-based transport and achieve peripheral distribution.
GROUP MEMBERS Ana Cunha (Post-doc) Raffaella Gozzelino (Post-doc) Susana Ramos (Post-doc) Rasmus Larsen (Post-doc) Zélia Gouveia (External PhD Student) Andreia Cunha (PhD Student) Nadja Pejanovic (PhD Student) Ivo Marguti (PhD Student) Bahtiyar Yilmaz (PhD Student) Sofia Rebelo (Laboratory Manager) Silvia Cardoso (Laboratory Assistant) COLLABORATIONS Josef Anrather (Cornell University, New York, USA) Leo Otterbein (Harvard Medical School, Boston, USA) Ann Smith (University of Missouri - Kansas City, USA) Ingo Bechmann (Johann Wolfgang Goethe-University, Germany) Yves Beuzard (Hospital Saint Louis, Paris, France) Liviu Vonaica, Lukas Kühn (Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland) Carlos Penha Gonçalves, Jocelyne Demengeot (Instituto Gulbenkian de Ciência, Portugal) Henrique Silveira (Instituto de Higiene e Medicina Tropical, Portugal) FUNDING Framework Programme 6 (FP6), European Commission Framework Programme 7 (FP7) - People, European Commission Fundação para a Ciência e Tecnologia (FCT), Portugal GEMI Fund Linde Healthcare, USA Bill & Melinda Gates Foundation, USA
PROTECTION AGAINST MALARIA BY "NATURAL" ANTIBODIES We are testing the hypothesis that antibodies directed against a specific carbohydrate produced by gut pathogens might play a role in immunity against severe forms of malaria. Newborns and young children, who are most susceptible to these severe forms of the disease, have not yet built up antibodies to this carbohydrate. We will assess whether stimulating production of this antibody after birth can offer increased protection.
MOLECULAR DISSECTION OF THE INTRACELLULAR ROUTE OF PLASMODIUM IN MACROPHAGES AND DENDRITIC CELLS The aim of this project is to study membrane trafficking pathways relevant to dendritic cell and macrophage function, using malaria infection as a model system. The malaria parasite is able to change the expression level of certain Rabs, such as Rab14, Rab27a, Rab32, on macrophages and dendritic cells. From these Rabs, Rab14 showed to be involved in the phagocytosis process of the malaria parasite by macrophages and dendritic cells.
REGULATION OF ADAPTIVE IMMUNITY BY HEME OXYGENASE-1 (HO-1) Over the past few years we extended our original studies to test the hypothesis that HO-1 might regulate T cell mediated autoimmunity leading to the pathogenesis of immune mediated inflammatory diseases such as diabetes, arthritis or multiple sclerosis (MS). We found that this is indeed the case for MS, where disease progression is caused by T cell driven neuroinflammation, leading to central nervous system injury. The mechanism underlying the protective effect of HO-1 against autoimmune neuroinflammation is not clear. We are testing the hypothesis that expression of HO-1 by antigen presenting cells, and in particular by dendritic cells, regulates their immunogenicity in a manner that arrests the pathogenesis of autoimmune diseases.
SUBVERSION OF THE HOST ENDOCYTIC PATHWAY BY PLASMODIUM SPOROZOITES We propose to study the role of the host hepatocyte endocytic and autophagic pathways during the course of malaria liver infection. We observed a strong association of autophagosomes around the parasite during the entire course of infection suggesting that the parasite is interacting with the host trafficking machinery. Functional depletion and pharmacological modulation of host autophagy lead to a strong effect on infection load as in parasite replication.
ANTI-ATHEROGENIC EFFECT OF HEME OXYGENASE-1: MECHANISM OF ACTION Expression of HO-1 exerts anti-atherogenic effects that are mediated, at least in part, by the production of the gasotransmitter carbon monoxide (CO). We have shown that the effect of CO is associated with it's ability to suppress the pro-inflammatory phenotype of monocyte/macrophage activation and to block smooth muscle cell (SMC) proliferation via a sequence of events that requires the activation of the p38 mitogen-activated protein kinases (MAPK). We aim to investigate whether inhaled CO can be used therapeutically to suppress the development of lipid-mediated atherosclerosis.
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EVOLUTION AND DEVELOPMENT Head: Élio Sucena PhD in Evolution and Development University of Cambridge, UK
Research in my lab focuses on evolutionary novelties. An evolutionary novelty consists of a new trait (either morphological, physiological or behavioural) that may open up the possibility of an adaptive radiation into new niches. We have been approaching this concept experimentally at different levels and with diverse methodologies. Specifically, we look into novelty at: 1. The genetic level, looking at gene function evolution upon gene duplication; 2. The cellular level, approaching immune cell function diversity in Drosophila; 3. The morphological level by studying the evolutionary origin of dorsal appendage formation in the Drosophila clade. DISSECTING THE DEVELOPMENTAL GENETIC BASIS OF EVOLUTIONARY NOVELTY We aim to establish the genetic basis for the origin of dorsal appendages in the eggshell of Drosophilids. We use the eggshell of Drosophilid flies as a model system for morphological novelty. The eggshell's dorsal appendages is a structure unique to the Drosophila lineage, and present throughout the lineage in various numbers, shapes and sizes. We have progressed in the establishment of a model that recapitulates the epithelial patterning, and with which we are now able to explore the number variation this structure displays across Drosophila species. In addition, our research into eggshell patterning of Ceratitis capitata, a species without dorsal appendages outside of the Drosophila clade, has led to a renewed understanding of the role played by the Dpp pathway during oogenesis.
GROUP MEMBERS Nelson Martins (Post-Doc) Alexandre Leitão (PhD student) Barbara Vreede (PhD student) Alexis Hazbun (MSc student) Vítor Faria (Research Technician)
EVOLUTION OF THE IMMUNE RESPONSE OF Drosophila melanogaster We aim to establish how adaptation to a type of pathogen in a particular life-stage or through a specific infection route shape the genetics of immune response. The mechanistic basis of the immune response in Drosophila has been widely studied, but little is known about the evolutionary and physiological mechanisms that drive local adaptation to pathogens, and whether this adaptation is dependent on factors such as the infected life-stage, route of infection, pathogen type or multiple infections, and the associated tradeoffs. An ongoing experimental evolution experiment in Drosophila, to different and contrasting immune challenges, will address these questions and provide insights into the genes and mechanisms involved in adaptation to pathogens.
COLLABORATIONS Claudine Chaouiya, Thiago Carvalho, Jocelyne Demengeot, Luis Teixeira (Instituto Gulbenkians de Ciência, Portugal) Adrien Fauré, Siegfried Roth (University of Koeln, Germany) Fernando Roch (Centre de Biologie de Development, France) Sara Magalhães (Universidade de Lisboa, Portugal) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal Instituto Gulbenkian de Ciência, Portugal
FUNCTIONAL EVOLUTION UPON GENE DUPLICATION This project aims to determine how recent gene duplicates acquire novel expression patterns. After performing a phylogenetic analysis and characterising the expression patterns of the Three Finger Domain Protein (TFDP) genes of the cluster III and V of Drosophila melanogaster, we have several instances of neo- and subfunctionalisation. We hypothesise that, in higher Diptera, TFDP genes have been co-opted by the ancestral eye development gene network. Different genes of this recently expanded family have been deployed in specific glial/neural cell subsets to participate in the highly dynamic process leading to the formation of both photoreceptor axonal tracks and their respective myelin sheaths. Further work will clarify the specific impact of regulatory evolution over the gene network driving the cellular mechanisms in the developing eye of holometabolous insects. ALTERNATIVE SPLICING AND GENE DUPLICATION IN THE EVOLUTION OF THE FOXP GENE SUBFAMILY We are investigating the evolutionary, structural and functional history of the FoxP gene family across metazoa. Through the integration of experimental and in silico studies of the FoxP gene subfamily across the animal kingdom, we have established a new model for the FoxP gene in invertebrates and for the vertebrate FoxP1 paralogue. Furthermore, we present a scenario for the structural evolution of this gene class and revealed new previously unsuspected levels of regulation for FoxP1 in the vertebrate system. IMMUNE CELL FUNCTION DIVERSITY IN DROSOPHILA This project aims to determine whether Drosophila plasmatocytes are structurally and functionally heterogeneous. We had previously shown that, contrary to the current view, Drosophila plasmatocytes (the functional analogues of vertebrate macrophages) constitute a heterogeneous population. For this we have established a novel protocol for hemocyte purification using a combination of GFP lines, specific staining and FACS analysis. Recently, we have shown that immune challenge leads to changes in total cell number and subset proportions. Moreover, using G-trace technique, we have determined that such changes are not due to shifts in cell identity but rather the result of differential proliferation and/or recruitment.
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Expression of Broad (red) in egg chambers of Zaprionus davidii (nucleus in green).
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HOST MICROORGANISM INTERACTIONS
EVOLUTIONARY GENETICS
Head: Luís Teixeira
Head: Henrique Teotónio
PhD in Biomedical Sciences Universidade de Lisboa, Portugal
PhD in Evolutionary Biology University of Cambridge, UK
Multicellular organisms and microorganisms are continuously interacting. Many of these interactions are mutually beneficial. However, multicellular organisms have to actively thwart invasion by opportunistic or overtly pathogenic microbes. We are studying the interaction of the model organism Drosophila melanogaster with different microorganisms, in particular intracellular ones. D. melanogaster has been successfully used as a model system to study innate immunity against many pathogens. Recently it has been shown that there are innate immunity pathways against viruses that conserved between insects and mammals. We are investigating mechanisms of resistance to viruses in the fruit fly. Interestingly, we have found that the intracellular bacteria Wolbachia confer resistance to RNA viruses in D. melanogaster. We want to understand the molecular basis of this induced resistance. Finally, we are interested in the interplay between Drosophila and Wolbachia itself. These endosymbionts are one of the most widespread intracellular bacteria in the world but little is known, at the molecular level, on how the hosts control Wolbachia or on how Wolbachia manipulate the hosts.
GROUP MEMBERS
Catarina Carmo (Post-doc) Álvaro Ferreira (Post-doc) Sabine Patot (Post-doc) Marta Marialva (Research Technician) Sara Esteves (Research Technician) Inês Pais (MSc student)
COLLABORATIONS
Francis Jiggins, Dean Baker (Department of Genetics, University of Cambridge, UK) Miguel Soares, Élio Sucena (Instituto Gulbenkian de Ciência, Portugal) Sara Magalhães (Faculdade de Ciências da Universidade de Lisboa, Portugal)
FUNDING Fundação para a Ciência e Tecnologia (FCT), Portugal
ANALYSIS OF WOLBACHIA PROTECTION AGAINST VIRUSES IN Drosophila melanogaster We will further characterise Wolbachia induced protection to viruses in order to better understand its mechanism. We will extend exisitng analyses by studying the interaction of Wolbachia with a larger panel of viruses. We will test the induction of viral resistance by different strains of Wolbachia. The purpose is to find how much variation exists in this phenotype and if this variation is correlated with other characteristics of the tested Wolbachia strains. Finally, an important unresolved question is if the induced protection is cell-autonomous. We will test if Wolbachia protection to viruses extends to Drosophila cells in culture and address this question. IDENTIFICATION AND CHARACTERISATION OF GENES INVOLVED IN Drosophila-Wolbachia INTERACTIONS Wolbachia infection may have profound effects in the biology of their hosts, ranging from parasitic manipulation of the reproductive biology of their host to a beneficial increase in their host’s resistance to viruses. Very little is known of the Wolbachia-host interaction at the cellular or molecular level. We will identify and characterise genes of D. melanogaster and Wolbachia involved in their interaction.
The objective of the Evolutionary Genetics group is to study the genetics of adaptation using experimental evolution, by testing current evolutionary theory. Adaptation and the study of natural selection and its consequences are central to any understanding of biology because they provide a comprehensive framework for the origin, divergence and maintenance of diversity. We use experimental evolution to integrate the study of variation at the phenotype level with the study of variation at the genotype level. Since setting up at the IGC, we have established experimental evolution populations of Caenorhabditis elegans, whose ecology is described by discrete non-overlapping generations at constant 10^4 census sizes, under benign resource conditions. These populations were manipulated to initially have levels of outcrossing and genetic diversity. Phenotyping is carried out at the level of fitness-proxies, life-history and RNA expression. Genome-wide linkage disequilibrium association mapping is carried out to determine the number and relative effects of the loci underlying adaptation. Numerical simulations are used to obtain the expected distributions of relevant statistics under the conditions of experimental evolution.
GROUP MEMBERS Ivo Chelo (Post-doc) Yoannis Theologidis (Post-doc) Sara Carvalho (PhD student) Bruno Afonso (PhD student) Christine Goy (Laboratory Manager) COLLABORATIONS Matt Rockman (New York University, USA) Boris Shraiman (University of California, Santa Barbara, USA) FUNDING European Research Council (ERC), European Commission Human Frontiers Science Programme (HSFP)
Our work with Drosophila melanogaster similarly addresses the genetic basis of adaptation by correlating the observed patterns of DNA sequence diversity with the phenotype distributions. In Drosophila we are particularly interested in understanding the process by which populations can revert to ancestral phenotype and genotype states, from standing genetic variation. Prelimiminary conclusions from our work with both model systems are that evolution from standing genetic variation may involve the non-linear interaction among large genomic regions, encompassing several functional ORFs, through within generation negative frequency dependence among them. In C. elegans, we have been able to observe the evolution of male function, indicative of their role promoting adaptation to novel environments, through increased outcrossing rates. Inbreeding depression does not per se explain the maintenance of androdioecy in this organism. Future avenues of research include the explicit modelling of adaptation in the laboratory from the details of population genetics.
DNA staining, with propidium iodide, of early Drosophila embryos. Large circles correspond to nuclei, smaller dots to the endosymbiotic bacteria Wolbachia.
THE INFLUENCE OF MATING, RECOMBINATION AND NATURAL SELECTION IN C. elegans EXPERIMENTAL EVOLUTION The aim of this project is to describe the population genetics of adaptation from standing genetic variation. We have completed the characterisation of >350 SNPs in experimentally evolved populations and the characterisation of reproduction and viability under several osmotic and anoxic environmental stress conditions. ROLE OF GENETIC INTERACTIONS AND RECOMBINATION IN EXPERIMENTAL EVOLUTION OF C. elegans We aim to determine the relation between patterns of associations among loci and the evolution of gene interactions. The derivation of three ancestral populations for experimental evolution with exclusive selfing, mixed selfing and outcrossing and obligatory outcrossing was achieved, as well as derivation of recombinant inbred lines from population at genetic equilibrium.
Drosophila adult gut infected with Drosophila C virus; Actin in red, DNA in blue, and virus in green.
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INNATE BEHAVIOUR
BACTERIAL SIGNALLING
Head: Maria Luísa Vasconcelos
Head: Karina Xavier
PhD in Neuroscience Universidade Nova de Lisboa, Portugal
PhD in Biochemistry Universidade Nova de Lisboa, Portugal
THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
Animals exhibit behavioural repertoires that are often innate and result in stereotyped sexual and social responses to their environment. Innate behaviours do not require learning or experience and are likely to reflect the activation of developmentally programmed neural circuits. We are interested in the nature of defined neural circuits: how activation of circuits elicits specific behaviours. In complex organisms it has been extremely difficult to study a circuit beyond the early stages of sensory processing. Drosophila melanogaster is an attractive model system to understand a circuit because flies exhibit complex behaviours that are controlled by a nervous system that is numerically five orders of magnitude simpler than that of vertebrates. We use a combined behavioural, genetic, imaging and electrophysiological approach to determine how defined neural circuits and their activation elicit specific behaviours.
GROUP MEMBERS
Ricardo Neto (Post-doc) Nélia Varela (Post-doc) Dennis Herrmann (Graduate Student) Nuno Martins (MSc Student) Sophie Dias (Research Technician) Joao Afonso (Research Technician)
FUNDING
Framework Programme 7 (FP7) Marie Curie Programme, European Commission Fundação para a Ciência e a Tecnologia (FCT), Portugal
FEMALE RECEPTIVITY Genetic studies have elucidated how Drosophila male courtship behaviour is specified and its circuit components are being dissected at a surprising speed. The circuit of female behaviour on the other hand has been largely uncharacterised. We use a behavioural protocol that allows us to selectively inactivate subsets of neurons in the adult flies only. We use this behavioural approach and combine it with anatomical and functional dissection of the circuit. We have focused our research on the neurons that express apterous. Inactivation of apterous expressing neurons leads to a marked reduction of receptivity of the female to the male’s courtship efforts. It is unlikely that all neurons that express apterous are involved in female receptivity. We have begun running experiments that allow us to zoom in on the apterous neurons that affect the behaviour of the female.
Bacteria use small chemical molecules called autoinducers to communicate with one another by a process called quorum sensing. This process enables a population of bacteria to regulate behaviours which are only productive when many bacteria act in concert as a group, similarly to what happens with multi-cellular organisms. Behaviours regulated by quorum sensing are often crucial for successful bacterial-host relationships whether symbiotic and pathogenic. In our laboratory biochemical and genetic approaches are used to study the molecular mechanisms underlying quorum sensing, with an emphasis on systems promoting bacterial inter-species communication. This research includes an integrated study involving elucidation of the chemical molecules that are used as signals, the network components involved in detecting the signals and processing information inside individual cells, and finally characterisation of the behaviour of the bacterial community in multispecies bacterial consortia. Our ultimate goal is to understand how bacteria use inter-species cell-cell communication to coordinate population-wide behaviours in consortia and in microbial-host interactions.
GROUP MEMBERS Fabio Rui (Post-doc) Michal Bejerano-Sagie (Post-doc) Catarina Pereira (PhD student) Rita Valente (PhD student) Paulo Correia (Trainee) COLLABORATIONS Stephen Miller (Swarthmore College) Rita Ventura, Pedro Lamosa (Instituto de Tecnologia Química e Biológica, Portugal) Isabel Gordo, Jocelyne Demengeot (Instituto Gulbenkian de Ciência, Portugal) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal
QUORUM SENSING IN Escherichia coli A variety of bacterial species possess a system called Lsr which enables them to sequester and process the AI-2 present in their environment. AI-2 is a broadly used signal for inter-species bacterial quorum sensing. Thus, bacteria that possess the Lsr system have the ability to quench inter-species quorum sensing and hence control important bacterial behaviours regulated by AI-2. We characterised the biochemical steps involved in this process. This knowledge opens the door to the potential exploitation of this natural mechanism as a means for controlling quorum sensing. Interference with inter-species cell-cell signaling can be particularly important when treating infections caused by multi-species biofilms that might rely on interspecies signals for persistence.
ACROSS SPECIES STRESS ODOR RESPONSE Stressed Drosophila melanogaster release an aversive odorant that elicits a robust avoidance response in test flies. Our data indicate that stress odor avoidance is not common to all Drosophilids. This behavioural difference between melanogaster and some of its sister-species provides a powerful framework to investigate how evolution has shaped distinct responses to an environmental cue, amenable to genetic, developmental and anatomical dissection. Stressed Drosophila melanogaster release an aversive odorant that elicits a robust avoidance response in test flies. Our data indicate that stress odor avoidance is not common to all Drosophilids. This behavioural difference between melanogaster and some of its sister-species provides a powerful framework to investigate how evolution has shaped distinct responses to an environmental cue, amenable to genetic, developmental and anatomical dissection.
IDENTIFICATION AND CHARACTERISATION OF QUORUM SENSING SYSTEMS INVOLVED IN BACTERIAL INTER-SPECIES COMMUNICATION The main goal of this project is to identify and characterise mechanisms of AI-2 detection and signal transduction pathways in the different species of bacteria that possess this system towards the understanding of the role AI-2 inter-species communication in multi-species environments. To determine the diversity of AI-2-signalling systems we used a combination of biochemical, genetic and bioinformatics approaches to identify the presence of functional AI-2 receptors in organisms with available genome sequences and tested these predictions experimentally. We demonstrate the presence of AI-2 receptors in most enteric bacteria but also in more distantly related bacteria as the plant symbiont Sinorhizobium meliloti, and the pathogen Bacillus anthracis. INHIBITION OF BACTERIAL PLANT VIRULENCE BY INTERFERENCE WITH INTERSPECIES CELL-CELL COMMUNICATION In this project we aim to identify the AI-2 receptor protein(s) and the molecular components involved in AI-2 dependent regulation of gene expression in Erwinia carotovora to determine its impact in virulence using the potato tuber infectious assay. We have performed a genetic screen to identify mutants impaired in quorum sensing dependent regulation of a virulence factor (production of the cell wall degrading enzyme pectin lyase).
THE FIGURE SHOWS THE TWO ANTENNAL LOBES (ALS) OF A Drosophila melanogaster. The V glomerulus has been photoactivated in the left AL and it is brighter than the V glomerulus in the right AL (arrowheads). The cell bodies that are connected to the left V glomerulus also became brighter after its photoactivation (arrows).
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Expression of a quorum sensing regulated promoter fused to GFP during the development of a Bacillus subtilis colony.
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RESEARCH FELLOWS
PLANT GENOMICS Head: Jörg Becker PhD in Biology University of Bielefeld, Germany
Our group is interested in the mechanisms underlying sexual reproduction and early embryogenesis with a particular focus on the role of the male gametes. Contrary to previous assumptions recent studies have shown that male gametes both in the plant and animal kingdom carry complex sets of RNA molecules, including not only mRNAs but also small RNAs. We are particularly interested in the role of these two RNA classes before, during and after double fertilisation as it occurs in higher plants. Using Arabidopsis thaliana as our primary experimental model we are addressing specific questions like: 1. What are the functions of small RNA and DNA methylation pathways in sperm cells? 2. Do sperm cell derived RNAs play a role after fertilisation? 3. Do conserved core sets of genetic modules underlie common characteristics of male gametes across kingdoms? We are also interested in understanding how proteins localised to the surface of male gametes control double fertilisation. Namely what are the molecular effectors involved in recognition and assuring two independent fusion events, and what is the relationship of these effectors with downstream signaling events leading to embryogenesis. In a second research line we have analysed the symbiotic transcriptome of the model legume Medicago truncatula.
GROUP MEMBERS Leonor Boavida (Post-doc) Filipe Borges (External PhD student) Patrícia Pereira (External PhD student) COLLABORATIONS Rob Martienssen (Cold Spring Harbor Laboratory, USA) Keith Slotkin (Ohio State University, USA) Ignacio Rubio Somoza (Max Planck Institute for Developmental Biology, Germany) Rui Gardner, Rui Martinho (Instituto Gulbenkian de Ciência, Portugal) Ji He (The Samuel Roberts Noble Foundation, USA) Carlos Plancha (Cemeare Lda, Portugal) Helge Küster (Leibniz University Hanover, Germany) Helena Carvalho (Instituto de Biologia Molecular e Celular, Portugal) Leonilde Moreira (Instituto Superior Técnico, Portugal) Sheila McCormick (US Department of Agriculture/Agricultural Research Service, USA) FUNDING Framework Programme 7 (FP7) - People Programme, European Commission Fundação para a Ciência e a Tecnologia (FCT), Portugal
THE ROLE OF SPERM DERIVED microRNAs DURING DOUBLE FERTILISATION IN ARABIDOPSIS We aim to decipher the potential role of sperm miRNAs for viability of the male gametes and, if being delivered to the female gametes upon fertilisation, for the regulation of early embryogenesis and endosperm development. We have identified potentially novel miRNAs and size variations of known miRNAs in sperm cells and pollen. Preliminary results indicate that an artificial miRNA delivered by the sperm cells can silence GFP expression in the zygote and early embryo. Moreover we have developed a highly efficient FACS protocol that allows us to isolate sperm cells and vegetative nuclei from pollen grains simultaneously. IDENTIFICATION OF CONSERVED GERM CELL SPECIFIC MODULES AS POTENTIAL PRECURSORS OF TOTIPOTENCY This project focuses on the identification of a conserved core set underlying the totipotent potential of the gametes through the functional analysis of transcripts encoding orthologue gene products in male gametes of plant, human and fly. We have isolated new Drosophila sperm samples since the original array data indicated contamination from adjacent tissues. The new data will be combined with our human and plant sperm data sets. THE SYMBIOTIC GENETIC PROGRAMME OF THE MODEL LEGUME Medicago truncatula This project aimed to provide a large-scale analysis of the symbiotic transcriptome of Medicago truncatula. The in depth analysis of datasets obtained for nodule and mycorrhizal symbioses is expected to foster the development of novel, testable hypotheses for diverse aspects of the genetic basis underlying the symbiotic program of leguminous plants, which constitute a key component of sustainable agricultural systems. We have finished processing a total of 153 samples (51 sample types) on Medicago GeneChips. Individual sets are being analysed by the project partners, but a complete release to the scientific community is planned for mid 2011 through incorporation in the Medicago Gene Expression Atlas.
LOCALISATION OF ARABIDOPSIS TETRASPANINS IN REPRODUCTIVE TISSUES AND GAMETES. Upper Left Panel - Heterozygous Pollen grain tetrad showing GFP localisation in the plasma membrane of sperm cells with both sperm nuclei stained in red (mRFP); Right Corner Inset - Structural detail of GFP expression in sperm cells but in a germinated pollen tube; Bottom Panel - Detail of female gametophyte expressing GFP in the plasma membrane of egg cell (right) and synergid cells (left); Right Panel - Nuclear localised transcriptional GFP fusion in sperm cells in a in vitro germinated pollen tube.
Transgenic Arabidopsis pollen grains expressing H2B-mRFP in the vegetative cell nucleus (red) and MGH3-eGFP specifically localised to the sperm cell nuclei (green) allow their co-purification by FACS.
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NETWORK MODELLING Head: Claudine Chaouiya
MOLECULAR AND FUNCTIONAL CHARACTERISATION OF SPERM-EXPRESSED PROTEINS WITH POTENTIAL FUSOGENIC ROLES DURING DOUBLE FERTILISATION IN Arabidopsis thaliana The project aims to identify sperm-expressed proteins with functions in double fertilisation to address fundamental questions underlying gamete fusion, e.g.: How do sperm and egg/central cells recognise each other and fuse and is there any specificity in these two different fusion events? What is the interplay, if any, between these proteins and the signaling mechanisms leading to the successful production of a seed? We have started to characterise the Arabidopsis tetraspanin gene family. Localisation studies of members of this family in male and female gametes seem to comfirm a possible role in gamete adhesion and fusion.
PhD in Computer Science University of Nice-Sophia Antipolis, France external website: http://compbio.igc.gulbenkian.pt/nmd/
Major breakthroughs in molecular biology, genomics and functional genomics pave the way to the understanding of regulatory mechanisms. Regulatory components interplay and operate at diverse levels (transcription and translation of the genetic material, protein modifications, etc.). Thereby, large and complex networks are delineated, providing a relevant functional framework for integrative studies of the control of cellular processes. To assess the behaviours induced by such networks, dedicated mathematical and computational tools are crucial. In this context, our goal is to develop generic and efficient means for the modelling and analysis of regulatory networks involving hundreds of components and diverse regulatory interactions, including inter-cellular signalling. For this, we mainly rely on a qualitative modelling framework that combines the generalised logical formalism and Petri nets. Mostly focusing on regulatory circuits, we aim at clarifying formal links between topological and dynamical properties. We further specify proper reduction, abstraction and (de) composition methods to tackle the modelling and analysis of large networks. We are now considering the application of model-checking and constraint programming to generate procedures easing the formulation of models that match experimentally observed behaviours.
GROUP MEMBERS Adrien Fauré (Post-doc) Beatriz Olivera (Post-doc) COLLABORATIONS Hanna Klaudel, Franck Pommereau (IBISC, France) Elisabeth Remy (Institut de Mathématiques de Luminy, Marseille, France) Elio Sucena, Jorge Carneiro (Instituto Gulbenkian de Ciência, Oeiras) Denis Thieffry (Ecole Normale Supérieure, Paris, France) Brigitte Kahn-Parles (TAGC Inserm U928, Marseille, France) Laurence Calzone (Institut Curie, Paris, France) Gregory Batt (INRIA Rocquencourt, France) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal Agence Nationale de la Recherche, France.
This theoretical work leads to the definition of computational methods that are then implemented either in our dedicated software GINsim, or in the form of standalone programmes. Finally, in close collaboration with biologists, we are eager to challenge systematically our methodological developments with real case applications, specifying and analysing models for the control of cell proliferation and differentiation. MALIN: MODULAR MODELLING AND ANALYSIS OF LARGE BIOLOGICAL INTERACTING NETWORKS The purpose of this project is to take advantage of modularity to define efficient computational methods for the modelling and analysis of regulatory processes in multi-cellular systems. Applications relate to the control of dorsal appendage formation during Drosophila oogenesis and of T lymphocyte differentiation in the periphery. On the one hand, a compositional modelling framework has been formalised in the context of the logical formalism. On the other hand, the regulatory mechanisms underlying the formation of the egg appendages in Drosophila have been investigated, giving rise to a large literature-based regulatory map and to a preliminary model in the form of a cellular automaton. CALAMAR: COMPOSITIONAL MODELLING AND ANALYSIS OF LARGE MOLECULAR REGULATORY NETWORKS - APPLICATION TO THE CONTROL OF HUMAN CELL PROLIFERATION The main goal is to define computational methods for network reduction and (de)composition and to relate qualitative and quantitative models by using abstraction techniques. These generic methods are applied to the modelling and analysis of a comprehensive map of the RB/E2F regulatory network. A reduction method of logical models of regulatory networks has been formalized and further implemented in GINsim. A redution method for chemical reaction models has also been implemented in BIOCHAM v3.0. Considering multi-cellular systems, we proposed a novel framework based on High level Petri nets facilitating the composition of regulatory modules accounting for neighbouring relations. The RB/E2F comprehensive map published in 2008 (Calzone et al. Mol Syst Biol. 4:173) has been significantly extended. A qualitative model focusing on the links between Rb and p53 pathways and the involment of E2F1 and E2F3 transcirption is almost completed.
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Screenshot of GINsim displaying the logical model of the regulatory network and signalling pathways controlling T helper cells differentiation (Naldi A. et al. PLoS Comput Biol 6(9) 2010).
Qualitative modelling approaches to understand egg appendage formation in Drosophila.
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LUPUS AND AUTOREACTIVE IMMUNE REPERTOIRES
NEURONAL STRUCTURE AND FUNCTION
Head: Constantin Fesel
Head: Inbal Israely
PhD in Immunology Université Paris VI / Institut Pasteur, France
PhD in Molecular and Medical Pharmacology University of California, Los Angeles THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
While the detection of molecular mechanisms as well as of genetic disease risk factors rapidly evolves, the systemic diversification of specificity repertoires, which is of obvious relevance for the pathogenesis of human autoimmune diseases, is still badly understood. In this situation, it is increasingly relevant to combine different types of knowledge in order to model the pathogenetic process that leads to autoimmune diseases as a whole, since they are known to depend on complex interactions of a variety of molecular and cellular mechanisms acting on different levels. Systemic Lupus Erythematosus (SLE) is a human autoimmune disorder where altered physiologies and self-reactive repertoires of both B- and T-cells are intimately connected. Autoreactive IgG antibodies are the diagnostic hallmark of SLE and diversify over long time periods before disease becomes manifest. However, this depends also on nonspecific factors, such as type I interferons. Our current approach is to model, in a stepwise fashion, the ways in which different genetic factors and molecular mechanisms are interconnected in SLE pathogenesis, by analysing their relatedness in reference to standardised and quantitative broad-spectrum immunoblot autoantibody profiles. In this context, we are particularly interested in the role of T-cell regulation. Since we found particular relations between antibody reactivity and regulatory T-cells in unaffected relatives of SLE patients, who often share elevated titres of SLE-associated auto-antibodies, we follow the hypothesis that these auto-antibody-positive unaffected relatives bear a particular capacity to regulate autoreactive immune repertoires that breaks down in clinically manifest disease. Consequently, our principal approach to model SLE pathogenesis is actually focused on genetic factors and molecular mechanisms relevant for T-cell regulation, in combination with a systematic study of first-degree relatives of SLE patients.
GROUP MEMBERS Nuno Costa (Research Technician / MSc Student) COLLABORATIONS Maria Berta Silva Martins (Instituto de Ciências Biomédicas Abel Salazar, Portugal) Carlos Vasconcelos, Margarida Lima (Hospital Geral de Santo Antonio, Portugal) Cristina João, Ana Elisabete Pires (Centro de Investigação de Patologia Molecular, Portugal) Carlos Ferreira, Maria Francisca Fontes (Hospital de Santa Maria, Portugal) José Alves (Hospital Fernando Fonseca, Portugal) FUNDING Fundação para a Ciência e Tecnologia (FCT), Portugal
FUNDING Champalimaud Foundation, Portugal
STRUCTURAL CORRELATES OF BIDIRECTIONAL CHANGES IN SYNAPTIC EFFICACY Synaptic potentiation leads to spine enlargement at individual synapses, and we aim to elucidate what are the structural consequences of synaptic depression at single spines. We will determine how bidirectional changes in synaptic strength correlate with structural modifications at the modified inputs, and whether these changes depend on new protein synthesis. We have induced long lasting synaptic depression through the activation of metabotropic glutamate receptors (mGluRs) in hippocampal organotypic slice cultures. We have imaged subsets of spines from these neurons for up to four hours. Additionally, we have initiated electrophysiological recordings from these cells in order to monitor the synaptic responses.
Example of an immunoblot membrane with blotted HEp-2 cytoplasmic proteins, and plasma from diverse subjects incubated in 28 vertical channels, where individual band patterns can be seen after reactivity visualisation using an alkaline phosphatase-labeled anti-human IgG and NBT/BCIP substrate development. Standardised quantitation is provided by a unique reactivity standard included in duplicates on each membrane (channel 10 and 20), and an additional quality control by a repeatedly tested sample (channel 26).
IGC ANNUAL REPORT ‘10
GROUP MEMBERS Yazmín Ramiro Cortés (Post-doc) Ali Ozgur Argunsah (PhD Student) Anna Hobbiss (PhD Student)
DENDRITIC COMPARTMENTALISATION OF PROTEIN SYNTHESIS-DEPENDENT SYNAPTIC PLASTICITY We aim to visualise structural changes that occur in living spines in response to protein synthesis dependent forms of activity. We will examine how activity at multiple spines leads to structural changes and changes in synaptic weights within a dendritic branch. We find that protein synthesis dependent stimulation of spines can facilitate plasticity at neighbouring spines for up to an hour and over long distances (70 um), using either cAMP agonists or through dopamine receptor activity. Spines can also compete for cellular resources if stimulated too closely together in time, and later stimulated spines can join the competitive process. These findings demonstrate that the spatial clustering of synapses provides greater computational power to a neuron.
LUPUS AND ITS COMPENSATION IN UNAFFECTED RELATIVES BY T-CELL REGULATION The aim of this project is to study the hypothesised compensation of potentially pathogenic effects of lupus-associated autoantibodies by regulatory T-cells in first-degree relatives of Systemic Lupus Erythematosus patients, in comparison with the patients themselves and unrelated control subjects. Regular sample collections are in progress, and preliminary observations are promising.
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We are interested in understanding how activity can lead to specific structural changes in neurons which may be important for learning, and how such changes affect connectivity within neural circuits. We would also like to understand how the structural diversity among neurons contributes to connectivity in the brain. The current focus is on single neurons, even single spines, to understand the cellular mechanisms that are important for synaptic plasticity and learning. Using 2-photon uncaging of glutamate together with live imaging of neurons, we are able to directly probe the structural consequences of activity at single inputs - as seen through changes in the size and shape of spines - as well as through changes in synaptic weights. Furthermore, by stimulating multiple neuronal inputs, we can begin to understand how spines cooperate or compete for the expression of plasticity within dendritic domains, and how local protein synthesis plays a role in these changes. Interestingly, several mental retardation disorders in humans are characterised by abnormal spine morphology together with alterations in protein translation. Studying neurons from animal models of these disorders may elucidate the mechanisms underlying the cognitive dysfunction, and shed light on the relationship between structure and function. By combining molecular and genetic tools together with imaging and electrophysiological methodologies, we investigate how information is physically stored in the brain.
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STRUCTURAL CORRELATES OF NATURALISTIC SPIKE TRAINS AT SINGLE SYNAPSES We aim to mimic naturally occurring patterns of activity with glutamate uncaging at individual spines, in order to determine what are the structural and plasticity correlates of these forms of activity. We will use this information to model neuronal information processing. Based on in vivo electrophysiological recordings from hippocampal CA3 neurons, glutamate uncaging protocols will be designed and used to stimulate individual spines on CA1 cells. We are developing software that will allow greater precision in the quantification of structural changes. Electrophysiological recordings in hippocampal organotypic slice cultures are underway in order to monitor the plasticity induced by the different stimulations.
IGC ANNUAL REPORT ‘10
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ACTIVATING SINGLE DENDRITIC SPINES. A fluorescent reporter is introduced into a subset of pyramidal neurons in cultured hippocampal brain slices so that individual spines can be visualised. Using 2-photon microscopy and photoactivation of caged glutamate, the neurotransmitter is released only at the site of stimulation. This allows us to examine how neurons modify individual synapses at which information is received. We can vary the type of stimulation delivered at a given input in order to mimic different forms of activity. Additionally, we can examine how experience at multiple synapses may become integrated, and what are the mechanisms which underlie such processing by the neuron.
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NEUROETHOLOGY LABORATORY
ANTIGEN PRESENTATION AND T CELL ACTIVATION
Head: Susana Lima
Head: Elisabetta Padovan PhD in Immunology University of Padova, Italy
PhD in Neuroscience University of Lisbon, Portugal THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
We are interested in the brain mechanisms underlying female mate choice, sexual behaviour and the interaction between the two. As animal model, we use wild-derived inbred house mice, which allow us to perform experiments that address evolutionarily-motivated questions in a controlled laboratory setting. We are currently investigating how females assess the quality of prospective mates and what aspects of experience shapes female choices. We are also actively developing new behavioural paradigms to measure and manipulate the variables that affect female sexual arousal and receptivity. To address our goal of understanding how patterns of neural activity give rise to these processes, we employ approaches ranging from electrophysiological recordings in behaving animals to genetic manipulation of neuronal networks. NEURONAL MECHANIMS FOR MATE CHOICE IN MICE Our main goal was to develop a behavioural paradigm of mate choice in mice to then investigate the neuronal mechanisms responsible for representing mates of different values and how comparison of competing alternatives are made. We have used a mate choice paradigm inspired by the natural situation observed in the hybrid zone between Mus musculus musculus and Mus musculus domesticus in Europe. We have established a mate choice paradigm with M. m. musculus and M. m. domesticus, where musculus females exhibit a strong and reliable preference for their own subspecies. We have also established that this preference is influenced by early imprinting mechanisms and it increases with multiple testing. Furthermore, the preference for a specific male is not absolute, but rather flexible and dependent of the alternatives that are available. NEURONAL MECHANISMS UNDERLYING SEX HORMONE-DEPENDENT SWITCHING OF SEXUAL RECEPTIVITY Female sexual receptivity changes across the reproductive cycle, being maximal during the fertile phase. This represents an interesting state-dependent behavioural output, where the interaction of sexual hormones and the physiology of neuronal circuits alters the way a female treats the same male stimulus. We are interested in understanding the role of the ventromedial nucleus of the hypothalamus (VMH) in the control of this receptivity switch. To this end, we are performing electrophysiological recordings of this area in naturally cycling female mice exposed to male stimuli. During the past year we have developed and troubleshooted electrophysiological recordings in the VMH of naturally cycling, freely moving females. We are able to record from well isolated neurons from this area, and we can observe stimulus triggered responses. We are currently testing other types of electrodes in order to increase the yeld of these experiments. FEMALE SEXUAL BEHAVIOUR: NEURONAL PATHWAYS FOR AROUSAL TERMINATION Like all behaviours, sexual arousal has a beginning and an end. Sensory genital stimulation received by the female during copulation (sensed by mechanoreceptors present in the cervix and clitoris) is relayed to the brain and is important for the rewarding effects of copulation and for its termination. Despite being a fundamental aspect of sexual behaviour, very little is known about how the brain integrates the genital stimulation received during copulation and how the brain uses this information to inhibit further sexual arousal. We have started by establishing a protocol to trace the genital input to the brain, by using pseudo rabies viruses (PRV) expressing green fluorescent protein. PRV infects axon terminals of neurons and after infecting a neuron, jumps to synaptically connected neuronal partners. By employing this method we are investigating which brain areas are synaptically connected to the genital organs that receive stimulation during copulation.
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GROUP MEMBERS Léa Zinck (Post-doc) Vanessa Urbano (Research Technician) COLLABORATIONS Marta Moita (IGC) FUNDING Framework Programme 7 (FP7) - People Programme, European Commission Bial Foundation, Portugal Champalimaud Foundation, Portugal
T cells are central actors of antigen-specific immune responses and their function is strongly influenced by the Antigen-presenting Cells (APC) they directly interact with. APC also control T cell activation indirectly by providing cytokines that depend on the local microenvironment where the cells reside and the type of trigger they recognise. Such environmental triggers are conserved molecular patterns sensed through Pattern Recognition Receptors (PRR). Although it has long been recognised that PRR on professional APC instruct the cell fate decisions of naïve T lymphocytes, a careful analysis of how PRR signalling modulates effector memory T cell function, directly and indirectly through APC, is still missing and is our main research interest.
GROUP MEMBERS Adrien Fauré (Post-doc) Beatriz Olivera (Post-doc) COLLABORATIONS Perrine Paul-Gilloteaux (Hospital de Santa Maria, Portugal) Claire Hivroz, Joao Eurico Cabral da Fonseca (Institut Curie, Paris, France) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal Agence Nationale de la Recherche, France.
In a healthy individual, T cell responses are tightly regulated and derangements in the activation of cytokine-producing T cells lead to autoimmunity. Such derangements may occur through inappropriate stimulation of tissueresident APC and/or effector CD4+ T helper (Th) cells. Hence, understanding how Monocyte/Macrophages modulate Th responses in the presence of PRR agonists it is of crucial importance for implementing effective vaccination strategies against a variety of human diseases.
HOUSE MICE IN EUROPE ARE DERIVED FROM A COMMON ANCESTOR ORIGINATING IN THE INDIAN SUBCONTINENT, WHICH SPREAD ACROSS EUROPE WITH THE SPREAD OF AGRICULTURE. Two subspecies have developed in allopatry: Mus musculus musculus and Mus musculus domesticus. Starting 6800 years ago, these two subspecies established a contact zone, spanning from Denmark to the Mediterranean.This hybrid zone exhibits assymetric mate choice, which in part has contributed to the still current separation of the two subspecies: while musculus females prefer to mate with musculus males, domesticus females mate indiscriminately. We have developed a behavioural paradigm in the laboratory using inbred wild derived animals of the subspecies musculus (PWD and PWK) and laboratory strains of mice (Black 6) as domesticus.
PWD FEMALES EXHIBIT A STRONG HOMOSUBSPECIFIC PREFERENCE FOR PWK MALES, RESEMBLING WHAT WE OBSERVE IN THE WILD. For 54 PWD females tested, we observed a significant, reproducible and robust preference for PWK over B6 males. The overall PI for PWK is strong and reproducible across individuals. Paired t-test:*** p<0.001.
We are assessing APC/T cell/PRR crosstalk in the human system with focus on Th cell subsets producing IL-17 (Th17), IFN-γ (Th1) or both. By combining advanced cell culture techniques, high-speed cell sorting, multicolor microscopy and bioinformatics we aim at the identification of specific subset(s) of non-professional APC capable of controlling the expansion of distinct Th cells, as well as their effector function. We first address and dissect the dynamics of this crosstalk in healthy individuals and then study whether they are conserved or lost in patients suffering of chronic inflammatory diseases. HOW PATTERN RECOGNITION RECEPTORS SIGNALING CONTROLS T LYMPHOCYTES ACTIVATION We first aim at the identification of distinct subset(s) of non-professional APC capable of controlling the expansion of cytokine-producing effector memory T cells and their effector function. Our second goal is to clarify the molecular events underlying those immuneregulatory effects. We have assessed the APC/T cell crosstalk established during antigen recognition. The cytokine production pattern induced in Th17 and or Th1 clones activated by M1 and M2 macrophages was assessed in 3D microscopy. Our imaging studies reveal that IL-17 and IFN-γ cytokines are contained in intracellular vesicles distributed around the Microtubule Organising Center (MTOC) of activated T cells, irrespective of the type of APC. Quantitative analysis of our 3D images using a bioinformatic tool we independently developed, demonstrates no differences in the number of intracellular cytokinecontaining vesicles and their cytokine load. Representative results obtained with a Th17 clone are shown in Figure 1. We are currently studying whether this pattern is maintained or lost in the presence of TLR-2 agonists.
AN EXAMPLE OF A PUTATIVE HYPOTHALAMIC NEURON THAT RESPONDED SELECTIVELY TO FEMALE PRESENTATIONS. Spike histogramme are shown (bin width = 1 sec). This neuron shows selective responses to the presentations of females from different strains. Colours indicate the time in which the stimuli are presented: Red - anesthetised female; Blue - anesthetised male; Yellow - a food pellet; Green - only plastic case (control condition); Gray - artifacts. Vertical axis shows firing rate (number of spikes per second); horizontal axis shows the time from the beginning of the session (in seconds).
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CYTOKINE PRODUCTION PATTERN IN ACTIVATED TH17 CELLS. A - 3D microscopy images show IL-17 (red) distributed around the T cell MTOC (green) within a human Th17 clone recognising TSST-1 on M1 (left) and M2 (right) Macrophages (blue). The quantitative analysis of up to 23 images plotted as total number of IL-17 containing vesicles (top) and vesicles average fluorescence intensity (bottom) is depicted in B.
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DOPAMINE IN ACTION LEARNING Head: Joseph Paton
basal ganglia cell types, we plan to express light sensitive channels and pumps in targeted locations within the basal ganglia circuit. Stimulating these proteins with light during experiments will provide us with two potentially powerful pieces of data. First, we will be able to ask what type of cell we are recording from in vivo much more easily and in higher volume than was available with older techniques. Second, we can test hypotheses about the role of activity in specific populations of neurons for timing behaviour.
PhD in Neurobiology and Behavior Columbia University, USA THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
The film director Elia Kazan once said that directing is “turning psychology into behaviour”. Your brain is charged with the same task every moment you are awake. Aside from reflexes, actions are almost always, at least initially, directed in nature. Disease states such as Parkinson’s disease, where voluntary action is inhibited, and obsessive compulsive disorder and drug addiction, where actions cannot be terminated, highlight the importance of proper direction of action for normal functioning.
GROUP MEMBERS Rui Azevedo (PhD student) Gustavo Mello (Research technician / PhD student) Sofia Soares (MSc student / Research Technician) COLLABORATIONS Joshua T. Dudman (Janelia Farm Research Campus, HHMI, USA) FUNDING Champalimaud Foundation, Portugal OPTOGENETIC IDENTIFICATION OF STRIATAL CELL-TYPE DURING TIMING BEHAVIOUR. We are working on selective viral-mediated ChR2 expression in striatal cell types. A - A fluorescent image from a coronal section of a D2Cre mouse brain (left) compared to a coronal mouse brain schematic (right) shows striatal D2 medium spiny neurons (MSNs) expressing ChR2– YFP following injection of Cre-dependent AAV into D2-Cre BAC transgenic mice. CPu - Caudate-putamen (striatum). B - Confocal image of ChR2–YFP-expressing neurons in the striatum (Arrow). C - Confocal image of To-Pro-3 staining in the same region as in panel B. D - Panels B and C merged. The white box indicates the region shown in panel E. E - Example of a spiny dendrite from a D2MSN expressing ChR2-YFP. Scale bars = (B, C and D) 15μm: (E) 5μm.
The core of my laboratory’s research is to advance our understanding of the neural mechanisms by which the actions that make up adaptive behaviour are learned and generated. Taking a cue from Mr. Kazan, we begin by developing well-controlled behavioural tasks for the investigation of signals related to temporal processing in the brain of awake-behaving rodent model systems. Currently, we are particularly interested in understanding how the neurotransmitter dopamine (DA) modulates neural functioning within the basal ganglia, an evolutionarily aged collection of structures historically thought of as being important for movement. In particular, DA appears important for normal timing of behavioural responses. Thus, we have developed simple cognitive tasks in rodents in which animals must learn to time intervals. Our approach employs multisite neurophysiological recordings, as well as theoretical, pharmacological, and molecular biological techniques. NEUROPHYSIOLOGY OF TIME ENCODING IN THE RODENT STRIATUM We aim to identify neural correlates of time intervals that rats estimate during performance of a novel timing task. In the past year, we continued this project by recording the spiking activity from single neurons while rats press a lever in order to gain rewards at defined intervals, classically called operant conditioning on a Fixed Interval (FI) reinforcement schedule. We have adapted the classical FI schedule in such a way that we can observe a behavioural readout that reflects the animals’ changing knowledge about time until reward. We have recorded from hundreds of neurons in the striatum, a major input area of the Basal Ganglia that has been implicated in timing. We find that the dynamics of neuronal activity across a population of neurons can be used to encode time over the range of tens of seconds to a minute. We developed decoding schemes to read out time relative to our task events on a moment by moment basis, and found that this moment by moment estimate covaried with a quantitative description of animals’ estimates of time until reward. These results should have far-reaching impact on our understanding of time encoding in the brain, as well as the field of associative and reinforcement learning. In addition this work provides a launching point for deeper investigation of the neural mechanisms of time encoding that we are developing in mice, where we have access to more molecular biological and genetic tools. OPTOGENETIC MANIPULATION OF DOPAMINE DURING TIMING BEHAVIOUR We plan to test the hypothesis that manipulation of Dopamine through physiologically realistic means alters timing performance and neural signals in the striatum. In addition we plan to determine the genetic identity of neurons during neurophysiology experiment to build more informed circuit models for how the basal ganglia functions during timing behaviour. In the past year, we have continued a parallel set of timing studies in mice in order to take advantage the increased molecular power of the mouse relative to the rat. We have trained mice on a classic temporal reproduction task, called the peak interval task, and the SFI task mentioned above. By combining viruses dependent on CRE recombinase activity for expression of transgenes, with mouse lines expressing CRE in specific
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NEUROPHYSIOLOGY OF TIME ENCODING IN THE RODENT STRIATUM. A - Scheme of the Serial Fixed Interval (SFI) lever pressing task. Rats and mice adjust pressing times in response to different fixed intervals (FI) of reinforcement. We analyse behavioural measures that co-vary with the time duration being sampled, such as the time of the first lever press after collecting a reward, that we refer to as “post reinforcement pause”. B Left - we calculated the median post reinforcement pause within blocks of trials of the same FI in a single session and on the right B Right - we show the density function of the pressing start times. We can see that rats vary their pressing start times in relation to the FI of reinforcement.
TUNING FOR TIME INTERVAL IN STRIATAL CELLS. Single neuron activity recorded during performance of the SFI task show variable response dynamics. The trial-averaged activity of 29 striatal neurons aligned on reward delivery is shown. Variable dynamics may be viewed as “tuning” for time interval just as neurons within sensory systems may be viewed as being tuned for stimulus characteristics. Models of how the brain might read out information about time from a population of such neurons for use in perception and learning are currently being explored in the lab.
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CARDIAC REGENERATION
EXTERNAL GROUPS
Head: Luís Rosário
GASTRULATION Universidade do Algarve, Portugal Head: José António Belo
THE FOLLOWING GROUPS DEVELOP THEIR RESEARCH AT EXTERNAL ASSOCIATED INSTITUTES AND RESEARCH CENTRES, MAINTAINING STRONG SCIENTIFIC COLLABORATIONS WITH IGC GROUPS AND ACCESS TO IGC FACILITIES
PhD in Medicine and Physiology University of Lisbon, Portugal
NEOANGIOGENESIS Instituto Português de Oncologia, Lisbon, Portugal and CEDOC-Centre for Chronic Diseases, Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Portugal Head: Sérgio Dias
The heart was considered a post mitotic organ until, in recent years, data first challenged this paradigm. Clinical observations first raised the possibility that cardiomyocyte renewal occurs: after myocardial infarction dividing cardiomyocytes were observed, and biopsies from human heart transplants with donor recipient sex mismatch, were shown to harbour newly formed cardiomyocytes from the recipient. Pathology observations, based on Carbon 14 to date the DNA from human biopsies, calculated the renewal rate of cardiomyocytes during the human lifespan. The paradigm change of the heart as a post-mitotic organ challenges our current knowledge of cardiovascular physiology, disease physiopathology and clinical therapy. We must now consider the mechanisms that keep organ homoeostasis, control proliferation, differentiation and physiologic integration of cardiac stem cells. Cardiac physiopathology must try to understand how a specific disease may affect these cells as well as the response of cardiac stem cells to the disease process itself. These findings may translate into novel therapies based on the use of cardiac stem cells to repair heart damage.
GROUP MEMBERS Laura Rodrigues (MSc Student) Adriana Gomes (MSc Student) Alex Matsuda (Trainee) Ana Marta Fonseca (Visiting Scientist)
EVOLUTIONARY ECOLOGY OF MICROORGANISMS Faculdade de Ciências da Universidade de Lisboa, Portugal Head: Francisco Dionísio
COLLABORATIONS Piero Anversa (Harvard Medical School)
VASCULAR DEVELOPMENT Faculdade de Medicina Veterinária, Universidade Técnica de Lisboa, Portugal Head: António Duarte
FUNDING Fundação Luso-Americana para o Desenvolvimento (FLAD), Portugal Fundação para a Ciência e a Tecnologia (FCT), Portugal Calouste Gulbenkian Foundation, Portugal
SYSTEMS IMMUNOLOGY University of Vigo, Spain Head: José Faro CELLULAR IMMUNOLOGY Instituto de Medicina Molecular, Fac. de Medicina da Univ. de Lisboa, Portugal Head: Luis Graça DEVELOPMENTAL BIOLOGY Instituto de Medicina Molecular, Fac. de Medicina da Univ. de Lisboa, Portugal Head: Domingos Henrique
Our focus is on gaining more in depth understanding of the mechanisms controlling maintenance, proliferation and differentiation of cardiac stem cells, to fully benefit from their potential.
TISSUE MORPHOGENESIS AND REPAIR Instituto de Medicina Molecular, Fac. de Medicina da Univ. de Lisboa, Portugal Head: António Jacinto
EVALUATION OF THE ABILITY OF CARDIAC, BONE MARROW AND UMBILICAL BLOOD CHORD PLURIPOTENT CELLS TO FUNCTIONALLY INTEGRATE INTO THE MYOCARDIUM The aim of this project is to isolate cardiac stem cells and identify their modifications in disease. We were able to isolate cardiac stem cells from embryonic, neonatal, adult and diseased hearts and to identify their different patterns of microRNA and protein expression, in order to characterise their phenotype.
MALARIA Instituto de Medicina Molecular, Portugal Head: Maria Mota AZORES GENETICS Divino Espírito Santo Hospital, Azores, Portugal Head: Luísa Mota Vieira GENOMICS OF COMPLEX DISEASES Instituto de Medicina Molecular, Fac. de Medicina da Univ. de Lisboa, Portugal Head: Sofia Oliveira
MOLECULAR STUDY OF HEART DEVELOPMENT AS A WAY TO UNDERSTAND CONGENITAL HEART MALFORMATIONS This project focuses on detecting new transcription factors and genetic markers involved in the embryonic development of the heart.
HAEMATOPOIESIS Faculdade de Medicina da Universidade de Lisboa, Portugal Head: Leonor Parreira
HERG DEPENDENT POTASSIUM CURRENTS CONTROL CARDIAC PROGENITOR CELLS Within this project the aims are to identify the influence of potassium currents in the control of cardiac stem cell proliferation and differentiation.
EMBRYONIC DEVELOPMENT OF VERTEBRATES Instituto de Medicina Molecular, Fac. de Medicina da Univ. de Lisboa, Portugal Head: Leonor Saúde MOLECULAR IMMUNOLOGY Instituto de Medicina Molecular, Fac. de Medicina da Univ. de Lisboa, Portugal Head: Bruno Silva Santos VIRAL PATHOGENESIS Instituto de Medicina Molecular, Fac. de Medicina da Univ. de Lisboa, Portugal Head: João Pedro Simas STRESS AND CYTOSKELETON Escola Superior de Tecnologia da Saúde de Lisboa, Portugal Head: Helena Soares DEVELOPMENT AND EVOLUTIONARY MORPHOGENESIS Faculdade de Ciências da Universidade de Lisboa, Portugal Head: Solveig Thorsteinsdóttir HUMAN MOLECULAR GENETICS AND FUNCTIONAL ANALYSIS UNIT Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon, Portugal Head: Astrid Vicente
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FACILITIES AND SERVICES
ANIMAL FACILITIES Head: Jocelyne Demengeot Group Leader - Lymphocyte Physiology Group
The Animal House Facility provides services to research groups using mice, rats, fish, flies and frogs as experimental models. The infrastructure is specialised into several areas, for each model organism. Equipment and infrastructure are funded by the Calouste Gulbenkian Foundation and the EMMA Consortium (mouse germ-free facility). THE RODENT FACILITY The Facility consists of five independent units: • A Production Facility; • Two Experimental Areas; • A quarantine and a Germ-Free Facility, which is part of the European Mouse Mutant Archive (EMMA) consortium. The Facility hosts more than 150 mouse strains and 2 rat strains. In 2010, 22 research groups used this Facility. Services offered include: housing, production, export and import of animals (including health tests), strain cleansing (rederivation), arquiving (of embryos and sperm), revitalisation, strain rescue, training (courses and specific sessions).
FACILITY STAFF Manuel Rebelo (Manager) Ana Mena (Animal Research Project Officer) Joana Bom (Technician) Rubina Caldeira (Technician) Ana Sofia Leocádio (Technician) Paulo Raimundo (Technician) Maysa Franco (Technician) Ana Maria Ramos (Technician) Carlos Pires (Caretaker - Production Unit) Samira Varela (Caretaker - Superviser E0 Unit) Graça Ramalho (Caretaker - Superviser E1 Unit) João Lopes (Caretaker - Superviser Quarantine Unit) Eusébia Varela (Caretaker) Cláudia Gafaniz (Caretaker) Autelinda Costa (Caretaker) Olinda Queirós (Caretaker) Luís Arroja (Caretaker) Jelskey Gomes (Caretaker)
THE RODENT FACILITY IS EQUIPPED WITH: • 7 autoclaves; • 15 IVCs (Isolated Ventilated Cages) rack system; • 6 Germ-Free Isolators; • 1 osmosis reverse system; • 1 vapor-phase hydrogen peroxide decontamination system; • 1 transfer and decontamination chamber; • 1 animal transfer chamber. The rodent facility is a member of two Framework Programme 7 (FP7) - funded projects: Infrafrontier and EMMA - The European Mouse Mutant Archive, through which it develops infrastructure for mouse breeding (including under germ-free conditions), analysis and archiving (via cryopreservation). THE FISH FACILITY The facility is composed of a quarantine room and an independent production/experimental area. All fish imported into the IGC are hosted in the quarantine and only eggs are introduced into the production/experimental zone. The facility includes a behaviour room and a microinjection room. In 2010 the fich facility hosted 22 zebrafish lines and was used by six research groups. Services offered include: housing, adult production, egg production, import of new lines. THE FISH FACILITY IS EQUIPEED WITH: • 1 ZebTEC system with 6 racks, total capacity of 300 tanks (3.5L); • 1 zebrafish system for Quarantine, capacity for 126 tanks (3.5L); • 2 microinjectors; • 2 microscopes; • 2 incubators at 28°C. THE FLY FACILITY The fly facility hosts several thousands of mutant lines that are available for research purposes. It is composed of several walk-in chambers, a food preparation room, 2 procedure labs and a quarantine set outside the Facility. During 2010, the Facility was used by nine research groups. Services offered include: food preparation (3 different receipes), fly room maintenance, stock tubes surveillance.
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TRANSGENICS FACILITY Head: Moisés Mallo
THE FLY FACILITY IS EQUIPPED WITH: • 18 work stations with CO2 output pedal system; • 2 working stations with CO2 output flow buddy system; • 1 microinjector; • 1 boiling pan for food preparation, 80L capacity; • 1 food dispensor; • 2 heat shock baths; • 1 room at 25°C; • 3 incubators at 25°C; • 1 behaviour room at 25°C; • 1 room at 18°C.
Group Leader - Patterning and Morphogenesis Group
THE FROG FACILITY This facility was set in 2010 and is used by one research group. It is composed of an aquatic habitat system for up to 140 Xenopus and a bench for related experimental work.
The Animal Facilities include state-of-the-art facilites for mouse (including a germ-free facility shown), fish and Drosophila, used by over 35 research groups, including axternal IGC groups.
The Transgenics Facility is the gene manipulation unit. The unit provides transgenic services to the research staff. Both classic transgenics, by pronuclear microinjection, and gene targeting, by blastocyst injection of embryonic ES cells, are offered as a service. The unit also offers the cryopreservation of embryos for long term storage.
FACILITY STAFF Ana Nóvoa (Research Technician) Joana Almeida (Research Technician)
THE FACILITY IS EQUIPPED WITH: • Microinjection setup with Nikon inverted microscope equiped with DIC optics, and three dimensional Narishige micromanipulators; • Microinjection setup with Leica inverted microscope equiped with DIC optics, and three dimensional, power assissted, Narishige micromanipulators; • 2 FemtoJet pumps; • Sutter P-87 Flaming/Brown micropipette puller; • Zeiss SV6 Stereomicroscope with training head; • 2 Standard Zeiss SV6 Stereomicroscopes; • CO2 incubator; • Ultrasonic Cleaning Device. Equipment and infrastructure are funded by the Fundação para a Ciência e a Tecnologia (Portugal) - Programa Nacional de Re-Equipamento Científico (National Programme for Scientific Re-Equipment), IGC.
TRANSGENIC MOUSE EMBRYOS.
MOUSE EMBRYOS AT THE TWO-CELL STAGE.
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PLANT FACILITY
CELL IMAGING UNIT
Users: Elena Baena-González (Plant Stress Signalling), Jörg Becker (Plant Genomics) Paula Duque (Plant Molecular Biology) José Feijó (Plant Development)
Head: José Feijó
The Plant Facility at the IGC ensures the growth and maintenance of Arabidopsis thaliana plants, the model organism used by the four plant research groups hosted by the Institute. The facility consists of a custom-built greenhouse with lighting control and temperature regulation and three custom-made fully controlled growth chambers with short day, long day and continuous light settings, as well as a walk-in plant growth room and a small reach-in chamber that allow the performance of cell-based assays and more precise phenotypic analyses.
Group Leader - Plant Development Group
FACILITY STAFF Vera Nunes (Technician)
Four research groups make use of the IGC Plant Facility, as all use Arabidopsis as a model system in their research work. The Plant Development group focuses on developing integrated models of cellular growth and morphogenesis using the pollen tube as a biological model, ion dynamics as an experimental paradigm and theoretical modeling as an integrative tool. The Plant Molecular Biology group investigates how plants perceive and respond to environmental signals and endogenous developmental cues at the molecular level, focusing on the role of pre-mRNA splicing in the regulation of gene expression. The Plant Stress Signaling group is interested in the mechanisms underlying tolerance to multiple types of stress and on how these signaling cascades interact with other physiological and hormonal cues to orchestrate growth and development. Finally, the Plant Genomics group is interested in the mechanisms underlying sexual reproduction and early embryogenesis with a particular focus on the role of the male gametes. THE FACILITY IS EQUIPPED WITH: • 1 Walk-in Chamber (Aralab 10.000 EH 2009); • 1 Reach-in Chamber (Aralab S600PLH);
The Cell Imaging Unit provides access to high-end technology and cuttingedge technical support for bioscience research. We provide a unique facility that allows ready access to a wide range of technologies and expertise in an integrated manner that helps drive research forward efficiently. The unit currently stands as an international reference laboratory for confocal and multi-photon microscopy, as well as for high-throughput cell sorting. The unit is well equipped, with two cell sorters, three confocal microscopes, a DeltaVision deconvolution microscope system and two multi-photon microscopes, besides a dozen more subsidiary and custom-made pieces of equipment.
FACILITY STAFF Carlos Tadokoro (Multi-photon Microscopy Applications Manager) Rui Gardner (Flow Cytometry Lab Manager) Nuno Moreno (General Coordinator Microscopy) Telma Lopes (Technician - Cell Sorting) Francisco Henrique (Technician - Microscopy) Pedro Almada (Technician - Microscopy)
Researchers are trained through regular workshops on basic and advanced light microscopy techniques as well as in flow cytometry and image acquisition software. All users receive basic training in the systems in use, in troubleshooting, and advice on experimental design. We have developed a strong and broad base of users and continue to train new users. Technical assistance is available when necessary to ensure collection of high quality images and analysis of data. Because microscopy is currently in high demand and new systems and techniques are continuously being developed to meet increasing scientific needs, we try to expand the facilities, to keep accessibility problems low, and introduce the latest innovations (in microscopy and flow cytometry) to the research community.
Reach-in chamber for cell-based assays and phenotypic analyses.
All equipment is funded by the IGC.
Walk-in plant growth room with Arabidopsis thaliana cultures.
THE FACILITY HAS THE FOLLOWING EQUIPMENT AT THE DISPOSAL OF RESEARCHERS: • Inspection wide-field light Microscopes: Olympus BH2, Olympus IMT-2, Leica DMLB2; • Research Widefield light Microscopes: Leica inverted DMIRE2, Leica upright DMRA2, Zeiss AxioImager M1; • Confocal microscopes: Leica SP5 (with resonant fast scanhead), Zeiss LSM 510 (with Meta detector), Andor Spinning disk (with EM-CCD intensified camera); • Multiphoton: Bio-Rad MRC 1024 with Coherent Mira-Verdi laser system; Prairie TPE microscope with Coherent Chameleon laser system (with double scanhead, can take the two lasers for simultaneous excitation/imaging); • DeltaVision - Deconvolution microscope system from Applied Precision, Inc. (full featured system with EM-CCD intensified camera); • Flow Cytometry Cell Sorters: MoFlo, FACSAria; • Flow Cytometry Analysers: FACSCan, FACSCalibur, CyAn ADP (3 lasers, 9 fluo-detectors) Beckman Coulter. IN 2010, THE UNIT DEVELOPED THE FOLLOWING PROJECTS: INTEGRATION OF A SCREENING MICROSCOPE This microscope is fully automated and works with open source software, being a good platform for on-the-fly analysis. The equipment uses fast filter wheels and shutters which, together with a sensitive CCD camera, enable three colour images in a 96 well plate in few minutes. For now, it has been used for automatic stitching, producing images of full brain mice or fish slices.
One of the three custom-built fully-controlled growth chambers.
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A NEW SCHEDULING SYSTEM The UIC has developed a new resource scheduling system. With this new system, a single equipment reservation can hold a waiting list enabling users to be automatically moved into a slot, in case of cancellation by a previously registered user. Users are warned by text message or e-mail of changes to their reservations. Another interesting feature is that users have to register entry onto the equipment and during usage period. This procedure aims to ensure that scheduled bookings are indeed used, thus avoiding no-use periods and risk of the equipment being left on overnight.
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CENOTYPING AND SEQUENCING UNIT Head: Carlos Penha-Gonçalves Group Leader - Disease Genetics Group
The Unit provides technological support and expertise for research at the genome scale and is composed of the Sequencing and Genotyping Services: • The Sequencing Service offers DNA sequencing and fragment analysis using multicapillary with automatic sequencer ABI 3130XL. Taqman® Technology in a 384-well format is also available to users both for SNP genotyping and Real-Time PCR gene expression with 7900 HT Fast RealTime PCR System; • The Genotyping Service offers the Sequenom iPLEX technology, allowing rapid SNP genotyping assays with up to forty SNPs assayed simultaneously. The facility collaborates with investigators on: SNP choice and SNP Assay Design, Sequenom Procedure and Data Management for Genetic Studies, providing access to the BC/GENE interface software.
FACILITY STAFF Maria Isabel Marques (Senior Laboratory Manager) João Costa (Research Assistant - Genotyping) Susana Ladeiro (Research Assistant - Sequencing)
• Genetic basis of morphological change in natural populations: Identifying candidate genes behind convergent evolution in blind cave fish Astyanax mexicanus; • Genetic predisposition to chronic inflammatory bowel disease and polyendocrinophaties in Tunisia; • Mouse genetic quality control; • Demographic and Genetic Responses to Habitat Fragmentation and Habitat Loss in Large Forest Mammals; • Dissecting the developmental genetics of evolutionary novelty; • Tuberculosis molecular epidemiology. Two IGC external groups used this service on the following projects: • Genetic Epidemiology of Autism (Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon); • Genetic factors involved in susceptibility to stroke and in outcome after 3 and 12 months (Instituto de Medicina Molecular, Lisbon); • Alzheimer's (Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon); • Genetic epidemiology of stroke in the post-genomic era (Instituto de Medicina Molecular, Lisbon). • BEDGET: deciphering Behçet’s Disease Genetics (Instituto de Medicina Molecular, Lisbon) Five external groups used the genotyping service: • Genetic Screening of Cardiomyopathies (Instituto de Medicina Molecular, Lisbon); • Evaluating the importance of the X-chromosome "large effect" in the initial stages of reproductive isolation between two pairs of divergent lagomorph taxa (CIBIO - Universidade do Porto); • Tuberculosis molecular epidemiology (Instituto de Ciências da Saúde, Brazil); • Wild bear (CIBIO, Universidade do Porto); • Osa genes (Instituto de Ciênicas Biomédicas Abel Salazar, Porto).
THE UNIT IS EQUIPPED WITH: • Two robotic pipetting devices, robot PlateMate 2x2 (Matrix); • Five thermocycling machines - ABI 9700 equipped with 2x384 blocks; • Chip spotting robot (MassARRAY, Nanodispenser); • SNP detection, MALDI-TOF technology - MassARRAY Compact (Sequenom); • ABI 3130XL; • 7900 HT Fast Real-Time PCR. All equipment was funded by the Fundação para a Ciência e Tecnologia (Portugal) - Programa Nacional de Re-Equipamento Científico (National Programme for Scientific Re-Equipment).
A total number of 2816256 SNP genotypes were produced between January 2010 and January 2011.
SEQUENCING SERVICE DNA SEQUENCING The ABI 3130XL Sequencing Service was used by thirty three internal groups, five IGC -associated groups (from the Instituto de Medicina Molecular, Lisbon) and two external laboratories (from the Faculdade de Ciências da Universidade de Lisboa and the Instituto de Química e Biologia, Lisbon). A total of 9 273 samples were sequenced during between January 2009 and January 2011. FRAGMENT ANALYSIS/MIRUS Nine internal groups used the ABI 3130XL Sequencing Service, on a total of 6406 samples between January 2010 and January 2011. FAST REAL-TIME PCR SYSTEM A total of 20 different projects made use of the 7900 HT PCR system on a regular basis (making up a total of 1062 hours), to detect gene expression of several genes. These included projects from: • twelve in-house research groups; • two IGC external groups: Instituto Português de Oncologia and Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon; • three external laboratories: Instituto Português de Oncologia, Instituto Superior de Agronomia and Faculdade de Ciências da Universidade de Lisboa, Lisbon. GENOTYPING SERVICE Eight internal group used the Genotyping Service on the following projects: • Mouse genetic quality control; • Genetics of Malaria in the Príncipe Population; • Genetic Susceptibility to Cerebral Malaria in Angolan Children; • Type 1 Diabetes: Genetic susceptibility; • Population genetics of adaptation in C. elegans; • Analysis of candidate genes involved in adaptation of reversed evolved populations of Drosophila melanogaster;
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GENE EXPRESSION UNIT
HISTOLOGY UNIT
Head: Jörg Becker
Head: Susana Lima
Research Fellow - Plant Genomics Group
Research Fellow - Neuroethology Laboratory
The Gene Expression Unit provides DNA microarray services, ranging from experimental design over complete sample processing to expert advice on data analysis. We are an Affymetrix Core Lab with reference status for GeneChip technology in Portugal since 2002. Running a total of 256 microarrays we have contributed to 23 in-house, national and international projects in 2010 alone.
FACILITY STAFF Júlia Lobato (Technician)
The Histology Unit provides a wide range of services related to tissue preparation. These include collection, fixation, processing, embedding, sectioning and staining of animal tissue samples. The unit also provides microscopy assistance as well as training to new users in sample preparation and sectioning.
FACILITY STAFF Ana Margarida Santos (Technician) Ana Gaspar (Technician; left Sept 2010) Joana Torres (Technician)
THE FACILITY HAS AT ITS DISPOSAL: • Equipment for chemical and cold fixation of animal and plant tissue; • Equipment for processing fixed tissue for light microscopy; • Equipment to embedding (paraffin, etc); • Cryostat, vibratome and microtome apparatus; • Equipments for Histochemistry, immunohistochemistry and immunofluorescence staining of tissues.
THE FACILITY IS EQUIPPED WITH: • Scanner 3000 7G with Autoloader *; • Fluidics Station 450 *; • Hybridization Oven 640; • Bioanalyzer 2100; • Affymetrix and Partek Genomics Suite software; • Hybridization Oven 640.
Equipment was funded by the Instituto Gulbenkian de Ciência (IGC).
* Equipment funded by Fundação para a Ciência e Tecnologia (Portugal) - Programa Nacional de Re-Equipamento Científico.
SERVICES PROVIDED INCLUDE: • Gene Expression Profiling (3’ IVT, Gene, Exon and Tiling arrays); • Genotyping, CNV (500K array set and SNP 6.0 array); • ChIP-on-Chip (Tiling arrays); • Custom array projects; • RNA and DNA quality analyses (Bioanalzyer); • Data analysis training (dChip and Partek Genomics Suite). THE FOLLOWING GROUPS USED THE FACILITY, IN 2010: • Plant Genomics - Truncatulix - 3 Medicago truncatula arrays; • Gene Expression Unit - Microarray course - 12 yeast arrays; • Malaria (IGC external group, IMM) - Malaria liver stage and type-I INFs - 6 mouse arrays); Malaria Lipids - 6 mouse arrays; • Cellular Immunology (IGC external group, IMM) - NKTreg - 10 mouse and human arrays; • Human Molecular Genetics and Functional Analysis Unit (IGC external group, Instituto Nacional de Saúde Dr. Ricardo Jorge) - Pool - 27 SNP arrays; • Applied and Environmental Mycology (ITQB) - GreenBio-Awake - 24 fungi custom arrays; • Control of Gene Expression Lab (ITQB) - BolA overexpression - 6 E. coli arrays; • Immunobiology Unit (IMM) - LSK expression - 6 human arrays; • Immunobiology Unit (IMM) - CD45+ expression - 12 human arrays; • Immunobiology Unit (IMM) - Expression upon activation - 6 mouse arrays; • GenoMed (IMM) - Cytogenetics - 1 cytogenetics array • Faculty of Pharmacy (Universidade de Lisboa) - Zinc finger - 12 human arrays; • Department of Genetics (Instituto Nacional de Saúde Dr. Ricardo Jorge) - Cyto - 4 cytogenetics arrays; • Biological Sciences Research Group (Instituto Superior Técnico) - Polymerization - 13 Burkholderia custom arrays; B. cenocepacia - 9 Burkholderia custom arrays; Herbitoxbioas - 15 yeast arrays; • Genomics and Plant Breeding (Instituto Superior de Agronomia) FuncGrape - 16 Vitis vinifera arrays; • Centro de Investigação de Patobiologia Molecular (IPO Lisboa) - Expressão génica de ATC10 - 10 human arrays; • Departement of Biology (University of Minho) - HairSpath - 6 human arrays; • Department of Biological Engeneering (University of Minho) - Synbiobacther - 4 E. coli arrays; • Plant-Microbe Interactions Group (CNRS-INRA Toulouse, France) - Truncatulix - 12 Medicago truncatula arrays; • Institute for Plant Genetics (Leibniz University Hanover, Germany) - Myc Factor - 36 Medicago truncatula arrays.
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Fluidics station for staining and washing up to 4 GeneChips in parallel.
Pseudo-coloured image of a GeneChip array after scanning, showing different signal intensities depending on the expression level of the correspondent transcripts.
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ION DYNAMICS FACILITY
BIOINFORMATICS AND COMPUTATIONAL BIOLOGY UNIT
Head: Ana Catarina Certal
Head: José Pereira Leal
Post-doc - Organogenesis Group
Group Leader - Computational Genomics Group
The Ion Dynamics Facility provides researchers with non-invasive technology for measuring electric currents and specific ion fluxes in biological systems. We are equipped with a Scanning Voltage Probe (SVET) and three Ion-Specific Probes (SIET), all from Applicable Electronics. Both probes are set-up in inverted fluorescence microscopes with high-resolution CCD cameras allowing the coupling of real-time electrophysiological measurements with intracellular ion imaging. In close collaboration with the Cell Imaging Unit, we also provide assistance and advice for advanced ion imaging using both commercial dyes or genetically-encoded ion probes. At present we have several projects being developed in plant development (pollen tube growth), fly development (drosophila oogenesis) and vertebrate organogenesis (zebrafish fin regeneration).
FACILITY STAFF Teresa Gomes (Research Technician)
THE FOLLOWING GROUPS USED THE FACILITY, IN 2010: • Evolution and Development; • Meiosis and Development; • Organogenesis; • Plant Development.
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FACILITY STAFF Maria Isabel Marques (Senior Bioinformatics Specialist) Paulo Almeida (Systems administrator & Programmer) Renato Alves (Systems administrator & Programmer) Isabel Neves (Researcher) Patrícia Soares (Programmer) Filipa Sousa (Visiting researcher)
IN 2010 THE UNIT WAS INVOLVED IN THE FOLLOWING PROJECTS: • HCO evolution, with the Metaloproteins and Bioenergetics lab (ITQB, Portugal). We hosted a visitor from this lab whom we trained and helped i) develop and validate a new protein classification scheme for Heme Coper oxidases, and implemente it as a web tool (http://www.evocell. org/hco) - submitted for publication. We further collaborated in developing an evolutionary study on the same superfamily of enzymes - also submitted for publication; • We are co-applicants with the Collective Dynamics group (IGC) and the Genomics Facility (IGC) on an FCT grant designed to establish a molecular framework for the epidemiology of tuberculosis in Portugal. We have developed and implemented a new web-based database and on-line analysis tool to support this project, the SIAM-TB: Sistema Informação e Análise Molecular - TB; • We are co-applicants, with several groups at the Laboratório Associado ITQB-IBET-IGC, on an FCT grant for the sequencing of the ESTs of the cork Oak, in response to a call by Government. The bioinformatics and computational biology unit has established an assembly and annotation pipeline to deal with the data produced by the multiple groups in the consortium, and is currently establishing the national cork oak database to enable the access and analysis of the ESTs, as well as showcasing the data to the wider scientific community; • Data warehousing environment for flow cytometry experiments. We developed and implemented the whole system, which has been submitted for publication. Other warehousing solutions are maintained in the unit for microarray data and microscopy images; • Direct-user support:18 IGC groups and 9 external groups received extensive support, which includes: finding mutations; transcription binding factors: Transfac; Genomatix; browsing genomes, finding genes, transcripts, proteins, SNPs, BLASTS, microRNAs, etc. Script design; finding homologues and orthologues; finding and analysing protein families; SNP analysis ; BCgene support; finding isoforms; finding genes for ear asymmetry – gallus; PhenomicDB database; assembly (Staden); codon usage; Force alignment; finding copy number variation; genes names diff Ids search; transcript identification, alignments, primers; clustering proteins according to protein families: domain searching; Scripts – Interpro searching; phylogenetic analysis; identifying and counting microRNAs in sequencing libraries; • Bioinformatics in high schools. We have developed an inquiry-based learning tool based on bioinformatics for high schools; teacher training; interaction with students. We are maintaining this system, adding functionality, and recruiting new schools and teachers to this experiment of using bioinformatics in the classroom. Eight schools are involved in the project: S. Miguel Torga, Queluz; E. S. Quinta do Marquês, Oeiras; EB3 Secundária Vila Cova da Lixa; E. S. José Afonso, Loures; E. S. Engº A. C. Duarte, Marinha Grande; E. S. Stuart Carvalhais, Queluz; E. S. de Mem Martins, Mem Martins and E. S. Luís de Camões, Lisboa.
THE FACILITY IS EQUIPPED WITH: • Two Ion-Specific Probe (SIET) setups coupled with an inverted fluorescence microscope (Nikon). SIET is equipped with a IPA-2 Ion/Polarographic Amplifier and Computerised Motion Control (CMC-4), all from Applicable Electronics, LLC. A Hamamatsu Camera controller and an illumination system by Lambda DG-4 provide image acquisition. Funded by Fundação para a Ciência e a Tecnologia (Portugal) and Fundação Calouste Gulbenkian (Portugal); • ASIET setup coupled with a zoom scope imaging unit. The SIET comprises an IPA-2 Ion/Polarographic Amplifier and Computerised Motion Control (CMC-4), all from Applicable Electronics. Funded by FP6 Network of Excellence "Cells into Organs", European Commisison; • A Scanning Voltage Probe (SVET) coupled with an inverted microscope (Nikon) equipped with a Phase Sensitive Detector Amplifier - 2 channel (PSDA-2), a Computerised Motion Control (CMC-4), all from Applicable Electronics, LLC. A Minicamera UK-1117-M CCD ensures image acquisition. Funded by Fundação Calouste Gulbenkian (Portugal).
FACILITIES AND SERVICES
Our unit's missions are to promote the use of computational methods in biological research, through training and development of resources and materials; to support the graduate programmes of the Oeiras Associated Laboratory (LAO); to provide direct user support in biological data analysis using computational methods and to conduct research and development in bioinformatics, in particular in data-flow, data warehousing and data analysis, supporting the LAO.
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PORTUGUESE BIOINFORMATICS CENTRE
RESEARCH FUNDING AFFAIRS
Head: Pedro Fernandes
Head: Sheila Vidal PhD in Physiology of Invertebrates Paris Sud XI University, Orsay, France
The Portuguese Centre for Bioinformatics (CPB-RAP) was created in 2005. It hosts hermes, a mid size cluster that is dedicated to Bioinformatics. Access to this cluster is free but users need an account. This is a high performance platform, therefore more suitable for heavy computations than for trivial jobs. To make good use of this machine, applications usually require deep modifications to allow for the use of the parallel processing capabilities.
FACILITY STAFF Daiane Tozzi (Undergraduate Trainee)
The Research Funding Affairs team was created in 2008 and is part of several support structures and services that the IGC has created for researchers to leverage international competiveness and scientific recognition.
FACILITY STAFF Mariana Guerreiro (Trainee) Andreia Reis (Trainee)
The Research Funding Affairs team is responsible for the implementation of a pre-award grant administration service. Its main goal is to increase the IGC’s capacity to attract research funds and to improve direct fundraising by research teams, and their scientific projects, for competitive calls launched by national, international, public and private grant programmes.
The facility is equipped with an IBM JS20 Blade computer (60), and associated control, management and storage, funded by Fundação para a Ciência e a Tecnologia (FCT) Re-equipment Programme.
This team reports directly to the IGC Director, understands the different grant financial policies and requirements and works in collaboration with researchers, project managers and finance staff.
THE FACILITY PROVIDED SUPORT OT SEVERAL PROJECTS IN 2010, INCLUDING: • Assigning multi-site genotypes to subpopulations - Marcos Antezana (Faculdade de Ciências da Universidade de Lisboa, Portugal); • MultiLocus Sequence Typing using eBURST goeBURST and new methods - João A. Carriço (Instituto de Medicina Molecular, Portugal); • MTBSS - Mycobacterium Tuberculosis Bioinformatic and Structural Strategies Towards Treatment - New Indigo - ERANET - Official start Sept 2010, with ITQB (Portugal) CIPF - Valencia (Spain), CDFD Hyderabad (India)
THE SERVICES OFFERED TO RESEARCHERS INVOLVE: • Identifying, in a timely manner, calls for proposals that might interest the IGC, evaluating the conditions and preferences for grant applications (eligibility, deadlines, how to apply and prepare full proposals, filling-in forms and web-pages, knowing how it works, what are the specific targets, what is behind each call, etc) and disseminating these opportunities through by several means: the Grant Information website, emails, meetings, etc; • Supporting proposal development and submission, namely: arranging administrative forms, host documents and signatures, assisting with scientific proposal writing and budget; • Post-award negotiation with funding agencies of contracts and agreements; • Grant application training for research staff and graduate students, namely those in the PhD programmes. In addition, this team also monitors the impact of the services offered through the quantification of the following criteria: number of applications submitted, secured grants and prizes, diversity of grant agencies and amounts raised. In 2010 this team supported researchers in attracting 62 new external competitive research grants (46: FCT; 7: EC-FP7; 9: other sources such as EMBO, AICR, HFSP, APCL, BIAL & CMO) to a total of 12,670.00 Euros. The Research Funding Affairs’ responsibilities cease with contract signature and after passing all grant information to the accounting department and researchers.
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INNOVATION AND TECHNOLOGY OFFICE
LIBRARY
Head: David Cristina
Head: Margarida Meira
PhD in Life Sciences University of California, USA
Technology Transfer (TT) is the exploitation, commercial or otherwise, of scientific research for the direct benefit of society. It's activities include sourcing invention disclosures, guaranteeing patent protection, licensing technologies, forming spin-out companies and managing consultancy opportunities for scientists. Technology Transfer is an undisputed source of social and economic growth internationally and an absolute necessity for institutions set on seeing their research have a direct, global impact on society, such as the IGC. Our Technology Transfer Office works as a liaison between industry and academia, facilitating communication between these two, very different, sectors. We offer several services to researchers, including: counseling on industry relations, assistance with intellectual property issues and sourcing of sponsored research agreements.
The Instituto Gulbenkian de Ciência library's collections covers biology, biochemistry, genetics, pharmacology, microbiology, physiology, immunology, virology, cell biology, neuroscience and developmental biology. It is an open access library, aiming to make available useful, diversified and up to date scientific information, and to acquire, register, maintain and distribute scientific information of interest to or produced by IGC researchers and students. The library is open to in-house users (researchers, faculty and visiting scientists, students and IGC staff), as well as to external users, from the scientific community or higher education institutions.
INFORMATICS
EQUIPMENT PURCHASING AND MAINTENANCE
Head: João Sousa
Head: Nuno Moreno
PhD in Theoretical Biochemistry Universidade de Lisboa, Portugal
PhD in Theoretical Biochemistry PhD in Biophysics Universidade Nova de Lisboa, Portugal
The Informatics unit at the IGC (ITI) manages most of the IT needs of the institute. We manage the IGC servers and network and provide various levels of support for the heterogeneous workstations and servers dedicated to research.
FACILITY STAFF Ana Carina Estêvão Amaro (Trainee)
The library's collection of printed journals spans almost 30 years. Currently it subscribes approximately 325 international journals in electronic format. In addition, through the national consortium Biblioteca do Conhecimento Online (b-on), it provides online access to approximately 22,000 international scientific journals and 18,000 e-books from 19 publishers, and through the Web of Knowledge, provides access to titles, abstracts, citation and impact factor reports of approximately 8,500 journals.
FACILITY STAFF João Garcia (Systems Analyst) Mário Neto (Junior Systems Administrator) Fernando Azevedo (Technician) Ana Maya (Technician) Manuel Carvalho (Technician)
We rely almost exclusively on Open Source for the services we provide. These services include E-Mail, VPN, printing, hosting of servers and services for researchers, administrative and collaborative Intranet services, central data storage, database and web site maintenance, surveillance and access control, consulting, training and, evidently, support.
The Equipment Management Unit is responsible for ensuring effective equipment acquisition, distribution and efficient usage. We work closely with technological facilities in order to provide cutting edge service and a smooth workflow, ensuring high equipment up time.
FACILITY STAFF Ana Homem (Research Tecnician) João Lagarto (Engineer)
Our services include: equipment repair and maintenance, building of small hardware apparatus, and several in house, open source systems, namely, an online resource scheduler, a small scientific database management system, a remote resource monitoring system. We are also trying to bring some of these products to market in order to help other facilities to improve their efficiency.
The IGC network infrastructure is almost exclusively gigabit, for servers and desktops, and we have full Wi-Fi coverage indoors and in selected outdoor areas. The IGC Internet connection is provided by FCCN Academic Network RCTS Services with a bandwidth of 50 Mbit/sec.
We run a seminar series "Tech Minutiae" with the aim of raising awareness, amongst scientists, of the most cutting edge techniques. We also work with the Direction of the institute in helping new labs set up, in terms of equipment and space management.
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Head: Maria Francisca Moraes Fontes MD, PhD
The mission of the IGC Ethics Committee is to review all research projects involving humans and animals to ensure that full consideration has been given to animal welfare and the ethical implications of the research. It is the Ethics Committee's responsibility to analyse all ethical issues that may arise during the course of the research projects developed by the groups or units of the IGC, including those specifically related to projects which engage studies with humans or animal research.
MEMBERS OF THE ETHICS COMMITTEE Maria Francisca Moraes Fontes, MD, PhD (Chairperson) Carlos Penha-Gonçalves, VD, PhD (IGC) Rui Costa, VD, PhD (IGC/Champalimaud Foundation) Manuel Rebelo, PhD (IGC) Ana Mena, PhD (IGC) Luís Pinheiro, MD (External Member) Ana Runkel (Oeiras City Council) José Athayde Tavares (Lawyer, External Member) Greta Martins, MBA (Assistant to the Director, IGC)
The Ethics Committee is an interdisciplinary body made up of nine members, three of whom are laypersons and four are external to the IGC.
ADMINISTRATION AND ACCOUNTS Head: José Mário Leite Deputy Director
This service provides support in all administrative matters, including ordering and stores, travel arrangements, auditoira and venue preparations, visitors, and new IGC researchers and students reception. The accounts office provides invaluable support in preparing financial reports of research projects, and in general management of accounts.
RESEARCH STRUCTURES
ETHICS COMMITTEE
FACILITY STAFF Teresa Meira (Direction Secretary) Fátima Mateus (Accounting Clerk) João Nunes (Accounting Clerk) Tatiana Rocha (Accounting Clerk) Vitor Santos (Accounting Clerk) Ana Lícia Pires (Accounting Clerk) Ana Maria Santos (Accounting Clerk) Jorge Costa (Office Clerk) António Bretanha (Purchasing Officer) Abílio Simões (Stores Manager) Teresa Sousa (Receptionist) Carlos Nunes (Driver) António Sousa (Maintenance Manager)
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NATIONAL AND INTERNATIONAL RESEARCH STRUCTURES
Centre for Developmental Biology Unit of the Fundação para a Ciência e a Tecnologia (Portugal) Head: Moisés Mallo
Laboratório Associado ITQB-IBET-IGC Director: José Artur Martinho Simões (ITQB Director)
The Centre for Developmental Biology was created in August 2003. The research programme currently involves more than 60 researchers, including 31 postdoctoral scientists, and integrates different research projects in the area of Developmental Biology within the IGC. The goal of this research centre is to understand the mechanisms that govern tissue and organ formation during normal embryonic development, their role in the origin of a variety of malformations and their possible applications for the design of novel therapeutic approaches. The research activities of the centre cover a wide spectrum of biological processes in Arabidopsis, Drosophila, Xenopus, chicken and mouse. The centre has collaborative projects with several Portuguese and foreign laboratories.
The Laboratório Associado ITQB-IBET-IGC brings together the Instituto de Tecnologia Química (ITQB), the Instituto Gulbenkian de Ciência (IGC), and the Instituto de Biologia Experimental e Tecnológica (IBET), in one of the first Associated Laboratories set up by the Ministry of Science and Technology, in 2001. The three institutes aim to carry out a collaborative research programme, underpinned by a strong communications network and sharing of infrastructures, namely libraries, scientific facilities, academic services, and administrative support. LAO research encompasses the following areas: biologically active molecules; complex disease genetics; developmental biology in animals and plants; evolutionary genetics; biological risk; plant and forest improvement; computational and theoretical biology.
In 2010, the centre maintained its standards of scientific excellence demonstrated in the previous years: the number of articles published by centre groups in international peer reviewed journals increased both in absolute number and, most importantly, in the level of the publications, with several articles in top reference journals, including Nature, Nature Genetics or Developmental Cell. Some of these publications describe discoveries of particularly relevant impact, which were the basis for the award of scientific prizes to members of the centre, such as the Pfizer Prize for Basic Research.
In 2010, research at the LAO involved 190 scientists (post-docs, group leaders), 172 PhD students, and a further 82 graduates, across the three research institutes. Genetics and Development of Natural Tolerance Unit of the Fundação para a Ciência e a Tecnologia (Portugal) Head: António Coutinho (IGC Director)
Members of the centre attracted impressive external funding in 2010. Apart from the high success rate of the different groups in the latest calls for scientific grants by the FCT (Portugal) and in the Harvard Medical School - Por-tugal programme, of note is the award of an ERC starting grant (worth 1.5 million for the next 5 years) to one of the centre groups (M. Bettencourt-Dias).
This Unit was created in 1999, and from it's inception, in 2000, has repeatedly been awarded the official rating of "Excellent" by the national Foundation for Science and Tecnology (FCT). This unit brings together just over 60 scientists at the IGC working in areas relevant to the understanding of the biological basis of autoimmune and inflammatory diseases. Research programmes focus on:
During 2010 the centre maintained a central role in the construction and functioning of the new fish and Xenopus facilities at the IGC, both of which have provided new biological and technological possibilities for the research performed by several of the groups.
1. The genetic, molecular and cellular mechanisms of inflammation and infections; 2. The interactions between innate and adaptive immunity; 3. Host-pathogen interactions; 4. Population dynamics of microorganisms.
The following IGC research groups belong to this Unit: • Elena Baena-González (Plant Stress Signaling) • Patrícia Beldade (Variation: Development and Selection) • Mónica Bettencourt Dias (Cell Cycle Regulation) • Paula Duque (Plant Molecular Biology) • José Feijó (Plant Development) • Miguel Godinho Ferreira (Telomeres and Genome Stability) • Florence Janody (Actin Dynamics) • Lars Jansen (Epigenetic Mechanisms) • Mathias Koeppen (Tissue Morphogenesis) • Moisés Mallo (Patterning and Morphogenesis) • Rui Martinho (Early Fly Development) • Joaquín Rodríguez León (Organogenesis) • Elio Sucena (Evolution and Development)
Scientists in the unit explore several experimental systems (flies and mice), while also addressing relevant questions in humans. The Unit has worked closely with several Portuguese patient groups, and maintains active collaborations with a variety of research groups and institutions, both in Portugal and abroad. The following IGC research groups belong to this Unit: • Alekos Athanasiadis (Protein-Nucleic Acids Interactions) • Vasco Barreto (Epigenetics and Soma) • Jorge Carneiro (Quantitative Organism Biology) • Jocelyne Demengeot (Lymphocyte Physiology) • Gabriela Gomes (Collective Dynamics) • Isabel Gordo (Evolutionary Biology) • Michael Parkhouse (Infection and Immunity) • Carlos Penha Gonçalves (Disease Genetics) • Miguel Soares (Inflammation) • Luís Teixeira (Host-Microorganism Interactions)
Champalimaud Foundation Neuroscience Programme at the IGC Head: Zachary Mainen The Champalimaud Neuroscience Programme (CNP) is a basic research team with the broad aim of understanding brain function through integrative biological approaches. CNP laboratories are using advanced molecular, physiological and imaging techniques to elucidate the function of neural circuits and systems in behaviour using animal models including Drosophila, mouse, rat and zebrafish. As of December 2010 the CNP comprises 12 independent research groups, including 7 in-house PIs, 3 Research Fellows and 2 associated External PIs. The CNP also organises the International Neuroscience Doctoral Programme (INDP). The CNP was created in 2007 through a collaborative agreement between the Champalimaud Foundation and the Calouste Gulbenkian Foundation.
The following IGC Research Fellows also belong to this Unit: • Claudine Chaouiya (Network Modelling) • Constantin Fesel (Lupus and Autoreactive Immune Repertoires) • Elisabetta Padovan (Antigen Presentation and T Cell Activation)
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In 2010 work from the CNP resulted in 13 refereed research articles, including reports on the neural basis of sequence learning (R. Costa) and circuitry for pheromone detection (L. Vasconcelos) published in Nature. This year, the CNP was also joined by two new investigators (M. Carey and M. Orger) and recruited four others who will join the programme in 2012. R. Costa and Z. Mainen received funding awards from the European Research Council, and Z. Mainen was honoured by election to the European Molecular Biology Organization (EMBO).
Patrice Milos (Helicos Biosciences, USA) August 2010 (RECOMB 2010) James Crutchfield (University of California Davis, USA) September, 2010 THE EUROPEAN MOUSE MUTANT ARCHIVE (EMMA) IGC Head: Jocelyne Demengeot
In-house Principal Investigators: • Rui Costa (Neurobiology of Action) • Zach Mainen (Systems Neuroscience) • Marta Moita (Behavioural Neuroscience) • Carlos Ribeiro (Behaviour and Metabolism) • Luísa Vasconcelos (Innate behaviour) • Megan Carey (Neural Circuits and Behaviour) • Michael Orger (Vision to Action)
The laboratory mouse is the most important mammalian model for studying genetic and multi-factorial diseases in Man. The European Mouse Mutant Archive (EMMA) is a non-profit repository for the collection, archiving (via cryopreservation) and distribution of relevant mutant strains that are essential for biomedical research. EMMA draws on the expertise of 11 leading research institutes across Europe, including the IGC, in Portugal. The IGC offers the crucial Germ-Free Service that generates, breeds and houses mice that are free of all microorganisms. These germ-free animals are crucial in studies aimed at understanding the effects of microorganisms on a host, or dissecting the molecular mechanisms underlying the function of the immune system.
Research Fellows: • Inbal Israely (Neuronal Structure and Function) • Susana Lima (Neuroethology) • Joe Paton (Dopamine in Action learning) External Principal Investigators: • Domingos Henrique (Developmental Biology) • Rui Oliveira (Animal Behaviour)
The germ-free facility of the IGC has generated more than 11 different strains of germ-free mice, requested by researchers from Portugal, Germany, USA, France and the UK. The facility has the capacity to temporarily host scientists wishing to carry out their own research with the mice at the IGC itself.
FLAD COMPUTATIONAL BIOLOGY COLLABORATORIUM Head: Luis Rocha
INFRAFRONTIER IGC Head: Jocelyne Demengeot
The chief aim of the FLAD Computational Biology Collaboratorium is to establish, enable, and foster an international, collaborative network of associated institutions and scientists. It is an open host organisation designed to enable intense cooperation amongst researchers from national and international institutions: the centre hub of a collaborative network of research institutions. It's chief aims are to provide suitable facilities for visiting scientists, and to host informatics technology to enable continuing off-site collaboration and research in mathematical and computational biology. The Collaboratorium operates in close synergy with the PhD Programme in Computational Biology: faculty is encouraged to stay longer periods of time to participate in work groups and collaborative projects hosted by the Collaboratorium. Likewise, visitors to the Collaboratorium are encouraged to give seminars and interact with students and faculty of the PhD Programme. Furthermore, the PhD programme will help identify research areas in mathematical and computational biology that are not yet sufficiently developed in Portugal. Reciprocally, the growing collaboration network fostered by the Collaboratorium, will facilitate the insertion of the newly formed computational biology PhDs within the Portuguese research and technology communities.
This consortium aims at building a world-class research infrastructure for mutant mice analysis and archiving, that provides the biomedical research community with the tools needed to unravel the role of gene function in human disease. In this frame, the grant supported the improvement of the legal status of the IGC rodent facility, for all issues related to vertebrate experimental models. It also allowed the Facility manager to visit several state-of-the-art facilities worldwide, for technical and managerial exchanges.
In 2010, the Collaboratorium hosted the following researchers in collaborative projects: Ruy Ribeiro (Los Alamos National Laboratory, USA) March 2010 Zvi Grossman (National Institutes of Health, USA) March 2010 Hagit Shatkay (Queen's University, Canada) June 2010 Rui Alves (Universidad Lleida, Spain) July-August, 2010 Mona Singh (Princeton University, USA) August 2010 (RECOMB 2010)
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PUBLICATIONS
PEER-REVIEWED PAPERS Anney R, Klei L, Pinto D, et al. (2010). A genome-wide scan for common alleles affecting risk for autism. Human Molecular Genetics 19(20):4072-4082. Antunes R and Moita MA. (2010). Discriminative auditory fear learning requires both tuned and nontuned auditory pathways to the amygdala. The Journal of Neuroscience.30(29):9782-7. Baena-González E. (2010). Energy Signaling in the Regulation of Gene Expression during Stress. Molecular Plant 3(2):300-313. Baptista FG, Pamplona A, Pena AC, Mota MM, Pied S, Vigário AM. (2010). Accumulation of Plasmodium-infected red blood cells in the brain is crucial for the development of cerebral malaria in mice. Infection and immunity 78(9):4033-9. Barclay JL, Kerr LM, Arthur L, Rowland JE, Nelson CN, Ishikawa M, d'Aniello EM, White M, Noakes PG, Waters MJ (2010). In Vivo Targeting of the Growth Hormone Receptor (GHR) Box1 Sequence Demonstrates that the GHR Does Not Signal Exclusively through JAK2. Molecular Endocrinology 24(1):204-217. Bray TC, Sousa VC, Parreira B, Bruford MW and Chikhi L. (2010). 2BAD: an application to estimate the parental contributions during two independent admixture events. Molecular Ecology Resources 10(3):538-541. Bergmann JH, Rodríguez MG, Martins NM, Kimura H, Kelly DA, Masumoto H, Larionov V, Jansen LE, Earnshaw WC. (2010) Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore. EMBO J 2010 Dec 14. Brito PH, Guilherme E, Soares H and Gordo I. (2010). Mutation accumulation in Tetrahymena. BMC Evolutionary Biology 10:354. Bruford MW, Ancrenaz M, Chikhi L, Lackman-Ancrenaz I, Andau M, Ambu L and Goossens B. (2010). Projecting genetic diversity and population viability for the fragmented orang-utan population in the Kinabatangan floodplain, Sabah, Malaysia. Endangered Species Research 12:249-261. Cachaco AS, Carvalho T, Santos AC, Igreja C, Fragoso R, Osorio C, Ferreira M, Serpa J, Correia S, Pinto-do-O P, Dias S. (2010). TNF-alpha Regulates the Effects of Irradiation in the Mouse Bone Marrow Microenvironment. PLOS ONE 5(2): Article Number: e8980. Caetano-Lopes J, Nery AM, Canhao H, et al. (2010). Chronic arthritis leads to disturbances in the bone collagen network. Arthritis Research & Therapy 12(1):R9. Campos I, Geiger JA, Santos AC, Carlos V, Jacinto A. (2010). Genetic screen in Drosophila melanogaster uncovers a novel set of genes required for embryonic epithelial repair. Genetics. 184(1):129-40. Carey MR, Regehr WG. (2010). Phosphatase activity controls the ups and downs cerebellar learning. Neuron 67(4):525-526. Carneiro T, Khair L, Reis CC, Borges V, Moser BA, Nakamura TM and Ferreira MG. (2010). Telomere Telomeres avoid end detection by severing the checkpoint signal transduction pathway. Nature 467(7312):228-232 (Press release). Carvalho IS, Cavaco T, Carvalho LM and Duque P. (2010). Effect of photoperiod on flavonoid pathway activity in sweet potato (Ipomoea batatas (L.) Lam.) leaves. Food Chemistry 118(2):384-390. Carvalho RF, Carvalho SD and Duque P. (2010). The plant-specific SR45 protein negatively regulates glucose and ABA signaling during early seedling development. Plant Physiology 154(2):772-783.
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Carvalho-Santos Z, Machado P, Branco P, Tavares-Cadete F, Rodrigues-Martins A, Pereira-Leal JB, Bettencourt-Dias M. (2010). Stepwise evolution of the centriole-assembly pathway. Journal of Cell Science 123(Pt 9):1414-26.
Domingues-Montanari S, Fernández-Cadenas I, Del Rio-Espinola A, Corbeto N, Krug T, Manso H, Gouveia L, Sobral J, Mendioroz M, Fernández-Morales J, Alvarez-Sabin J, Ribó M, Rubiera M, Obach V, Martí-Fàbregas J, Freijo M, Serena J, Ferro JM, Vicente AM, Oliveira SA, Montaner J. (2010). Association of a Genetic Variant in the ALOX5AP with Higher Risk of Ischemic Stroke: A Case-Control, Meta-Analysis and Functional Study. Cerebrovascular Diseases 29(6):528-537.
Cheng C, Noorderloos M, van Deel ED, Tempel D, den Dekker W, Wagtmans K, Duncker DJ, Soares MP, Laman JD, Duckers HJ. (2010). Dendritic Cells Function in Transplantation Arteriosclerosis Is Regulated by Heme Oxygenase 1. Circulation Research 106(10):1656-1666.
Duarte IM, Almeida MTM, Derek JFB, Marques I, Neilson R, Decraemer W. (2010). Phylogenetic relationships, based on SSU rDNA sequences, among the didelphic genera of the family Trichodoridae from Portugal. Nematology. 12(2): 171-180. Duarte J, Agua-Doce A, Oliveira VG, Fonseca JE, Graca L. (2010). Modulation of IL-17 and Foxp3 Expression in the Prevention of Autoimmune Arthritis in Mice. PLOS ONE 5(5): e10558.
Cheung AY, Boavida LC, Aggarwal M, Wu H-M and Feijó JA. (2010). The pollen tube journey in the pistil and imaging the in vivo process by two-photon microscopy. Journal of Experimental Botany 61(7):1907-1915. Chikhi L, Sousa V, Luisi P, Goossens B and Beaumont MA (2010). The Confounding Effects of Population Structure, Genetic Diversity and the Sampling Scheme on the Detection and Quantification of Population Size Changes. Genetics 186(3):983-U347.
Dzhindzhev NS, Yu QD, Weiskopf K, Tzolovsky G, Cunha-Ferreira I, Riparbelli M, Rodrigues-Martins A, Bettencourt-Dias M, Callaini G and Glover DM. (2010) Asterless is a scaffold for the onset of centriole assembly. Nature 467(7316):714-18.
Conine CC, Batista PJ, Gu WF, Claycomb JM, Chaves DA, Shirayama M, Mello CC. (2010). Argonautes ALG-3 and ALG-4 are required for spermatogenesisspecific 26G-RNAs and thermotolerant sperm in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America 107(8):3588-3593.
Epiphanio S, Campos M, Pamplona A, Carapau D, Pena AC, Ataide R, Monteiro C, Felix N, Costa-Silva A, Marinho C, Dias S, Mota M. (2010). VEGF Promotes Malaria-Associated Acute Lung Injury in Mice - art. no. e1000916. PLOS Pathogens 6 (5):916. Feijó JA (2010). The mathematics of sexual attraction. Journal of Biology. 9(3):18.
Correia CT, Coutinho AM, Sequeira AF, Sousa IG, Venda LL, Almeida JP, Abreu RL, Lobo C, Miguel TS, Conroy J, Cochrane L, Gallagher L, Gill M, Ennis S, Oliveira GG, Vicente AM. (2010). Increased BDNF levels and NTRK2 gene association suggest a disruption of BDNF/TRKB signaling in autism. Genes, Brain and Behavior 9(7):841-848.
Feierstein CE, Mainen ZF. (2010). Listening to the crowd: neuronal ensembles rule. Neuron 66(3):438-448.
Correia CT, Almeida JP, Santos PE, Sequeira AF, Marques CE, Miguel TS, Abreu RL, Oliveira GG, Vicente AM. (2010). Pharmacogenetics of risperidone therapy in autism: association analysis of eight candidate genes with drug efficacy and adverse drug reactions. Pharmacogenomics 10(5):418-430.
Fernandes P.(2010). The GTPB training programme in Portugal. Briefings in Bioinformatics 11(6):626-634.
Cortez AMM, Boggio G, Guerra MD, de Gavidia MR, Reyes GCR, Ferrer E, Lares M, Alviarez Y, Harrison LJS and Parkhouse RME (2010). Evidence that active transmission of porcine cysticercosis occurs in Venezuela. Tropical Animal Health and Production 42(3):531-537.
Fokkens L, Botelho S, Boekhorst J, Snel B. (2010). Enrichment of homologs in insignificant BLAST hits by co-complex network alignment. BMC Bioinformatics 11. Article Number: 86. Galhardo L, Vital J and Oliveira RF. (2010). The role of predictability in the stress response of a cichlid fish. Physiology and Behavior 2010 Dec 9 [Epub ahead of print].
De Rosa M, de Sanctis, Rosário AL, Archer M, Rich A, Athanasiadis A, Carrondo MA. (2010) Crystal structure of a junction between two Z-DNA helices. Proceedings of the National Academy of Sciences of the United States of America 107 (20):9088-9092. Debec A, Sullivan W, Bettencourt-Dias M. (2010) Centrioles: active players or passengers during mitosis? Cellular and molecular life sciences 67(13): 2173-2194.
Gomes A, Correia D, Grosso A, Lanca T, Ferreira C, Lacerda J, Barata J, da Silva M, Silva-Santo, B. (2010). Identification of a panel of ten cell surface protein antigens associated with immunotargeting of leukemias and lymphomas by peripheral blood gamma delta T cells. Haematologica-the Hematology Journal 95(8):1397-1404.
Derusso AL, Fan D, Gupta J, Shelest O, Costa RM, Yin HH. (2010). Instrumental uncertainty as a determinant of behavior under interval schedules of reinforcement. Front Integr Neurosci 28(4):17.
Gomes AL, Carvalho T, Serpa J, Torre C , Dias S. (2010). Hypercholesterolemia promotes bone marrow cell mobilization by perturbing the SDF-1:CXCR4 axis. BLOOD 115(19):3886-3894 (Press release). Gonçalves J, Nolasco S, Nascimento R, Fanarraga ML, Zabala JC, Soares H. (2010). TBCCD1, a new centrosomal protein, is required for centrosome and Golgi apparatus positioning. EMBO Reports 11(3):194-200.
Dias-Ferreira E, Sousa N and Costa RM. (2010). Frontocerebellar Connectivity: Climbing through the Inferior Olive. Frontiers in Neuroscience 4:37. Didier G, Remy E and Chaouiya C. (2010). Mapping multivalued onto Boolean dynamics. J Theor Biol 2010 Sep 22 [Epub ahead of print].
Goncalves D, Saraiva J, Teles M, Teodosio R, Canario AVM and Oliveira RF. (2010). Brain aromatase mRNA expression in two populations of the peacock blenny Salaria pavo with divergent mating systems. Hormones and Behavior. 57(2):155-161.
Djokovic D, Trindade A, Gigante J, Badenes M, Silva L, Liu R, Li X, Gong M, Krasnoperov V, Gill P, Duarte A. (2010). Combination of Dll4/Notch and Ephrin-B2/EphB4 targeted therapy is highly effective in disrupting tumor angiogenesis. BMC CANCER 10: Article Number: 641
Goncalves-Sousa N, Ribot JC, Barros A, Correia D, Caramalho I, Silva-Santos B. (2010). Inhibition of murine gamma delta lymphocyte expansion and effector function by regulatory alpha beta T cells is cell-contact-dependent and sensitive to GITR modulation. European Journal of Imunology 40(1):61-70.
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Gonzalez LM, Bailo B, Ferrer E, Fernandez Garcia MD, Harrison LJS, Parkhouse MRE, McManus DP and Garate T. (2010) Characterization of the Taenia spp HDP2 sequence and development of a novel PCR-based assay for discrimination of Taenia saginata from Taenia asiatica. Parasites & Vectors 3:51. Gozzelino R, Jeney V and Soares MP. (2010). Mechanisms of cell protection by heme oxygenase-1. Annual Review of Pharmacology and Toxicology 50:323-54.
Liehl P, Franca AR, Prudencio M, Latz E, Zaidman-Remy A, Mota M. (2010). Phosphothioate oligodeoxynucleotides inhibit Plasmodium sporozoite gliding motility. Cellular Microbiology 12(4):506-515. Lopes S, Lourenco R, Pacheco L, Moreno N, Kreiling J, Saude L. (2010). Notch signalling regulates left-right asymmetry through ciliary length control. Development 137(21):3625-3632. Fanarraga M, Carranza G, Castano R, Nolasco S, Avila J, Zabala J. (2010). Nondenaturing Electrophoresis as a Tool to Investigate Tubulin Complexes. Methods in Cell Biology (95):59-75.
Guerra-Assuncao, Jose Afonso, Enright, Anton J. (2010). MapMi: automated mapping of microRNA loci. BMC Bioinformatics 11: Article Number: 133. Guerrero A, Nishigaki T, Carneiro J, Tatsu Y, Wood CD and Darszon A. (2010). Tuning sperm chemotaxis by calcium burst timing. Developmental Biology 344(1):52-65.
Lacava R, Brasileiro L, Maia R, Oliveira R, Macedo R. (2010). Social environment affects testosterone level in captive male blue-black grassquits. Hormones and Behavior 2010 Oct 13 [Epub ahead of print]. Loueslati B, Troudi W, Cherni L, Rhomdhane K, Mota-Vieira L. (2010). Germline HVR-II mitochondrial polymorphisms associated with breast cancer in Tunisian women. Genetics and Molecular Research 9(3):1690-1700.
Guerrero A, Wood C, Nishigaki T, Carneiro J and Darszon A. (2010). Tuning sperm chemotaxis. Biochemical Society Transactions 38:1270-1274 Part 5. Hendrix A, Maynard D, Pauwels P, Braems G, Denys H, Van den Broecke R, Lambert J, Van Belle S, Cocquyt V, Gespach C, Bracke M, Seabra MC, Gahl WA, De Wever O, Westbroek W. (2010). Effect of the Secretory Small GTPase Rab27B on Breast Cancer Growth, Invasion, and Metastasis. J Natl Cancer Inst. 102(12):866-80.
Lourenco A, Carreira R, Glez-Pena D, Mendez JR, Carneiro S, Rocha LM, Diaz F, Ferreira EC, Rocha I, Fdez-Riverola F, Rocha M. (2010). BioDR: Semantic indexing networks for biomedical document retrieval. Expert Systems with Applications 37(4):3444-3453.
Henrique D, Bally-Cuif L. (2010). A cross-disciplinary approach to understanding neural stem cells in development and disease. Development 137(12):1933-1938.
Lunzer M, Golding GB, Dean AM. (2010). Pervasive Cryptic Epistasis in Molecular Evolution. PLOS Genetics 6(10): Article Number: e1001162.
Hilty M, Burke C, Pedro H, Cardenas P, Bush A, Bossley C, Davies J, (Ervine, A), Poulter L, Pachter L, Moffatt M, Cookson W. (2010). Disordered Microbial Communities in Asthmatic Airways. PLOS ONE. 5(1): Article Number: e8578.
Mallo M, Wellik DM and Deschamps J. (2010). Hox genes and regional patterning of the vertebrate body plan. Developmental Biology 344(1):7-15. Manso H, Krug T, Sobral J, Albergaria I, Gaspar G, Ferro JM, Oliveira SA, Vicente AM. (2010). Variants of the Matrix Metalloproteinase-2 but not the Matrix Metalloproteinase-9 genes significantly influence functional outcome after stroke. Medical Genetics 11: 40. Marais G, Campos P, Gordo I. Can intra-Y gene conversion oppose the degeneration of the human chromosome? A simulation study. Genome Biology and Evolution 2:347-357.
Hviid L, Marinho CRF, Staalsoe T and Penha-Goncalves C. (2010) Of mice and women: rodent models of placental malaria. Trends in Parasitology. 26(8):412-419. Jin X, Costa RM. (2010) Start/stop signals emerge in nigrostriatal circuits during sequence learning. Nature. 466(7305):457-462 (Press release). Johnson HA, Goel A, Buonomano DV. (2010). Neural dynamics of in vitro cortical networks reflects experienced temporal patterns. Nature Neuroscience. 13(8):917-9. Kolchinsky A, Abi-Haidar A, Kaur J, Hamed AA, Rocha LM. (2010). Classification of protein-protein interaction full-text documents using text citation network features. IEEE - ACM Transactions on computational Biology and Bioinformatics. 7(3):400-411. Kretzschmar M, Gomes MGM, Coutinho, RA and Koopman JS. (2010). Unlocking pathogen genotyping information for public health by mathematical modeling. Trends in Microbiology. 18(9):406-412.
Rodrigues-Martins A, Machado P, Callaini G, Bettencourt-Dias M. (2010). Microscopy methods for the study of centriole and function in Drosophila. Methods in Cell Biology 97:223-242. Matos I, Machado MP, Sucena E, Collares-Pereira MJ, Schartl M, Coelho MM. (2010). Evidence for Hermaphroditism in the Squalius alburnoides Allopolyploid Fish Complex. Sexual Development 4(3):170-175. Mena AL, Lam EW, Chatterjee S.(2010). Sustained spindle-assembly checkpoint response requires de novo transcription and translation of cyclin B1. PLoS One 28;5(9) pii: e13037.
Krug T, Manso H, Gouveia L, Sobral J, Xavier JM, Albergaria I, Gaspar G, Correia M, Viana-Baptista M, Simões RM, Pinto AN, Taipa R, Ferreira C, Fontes JR, Silva MR, Gabriel JP, Matos I, Lopes G, Ferro JM, Vicente AM, Oliveira SA.(2010). Kalirin: a novel genetic risk factor for ischemic stroke. Human Genetics. 127(5):513-523.
Mira N, Becker J, Sa-Correia I. (2010). Genomic Expression Program Involving the Haa1p-Regulon in Saccharomyces cerevisiae Response to Acetic Acid. OMICS - A Journal of Integrative Biology 14(5):587-601. Monteiro M, Almeida C, Caridade M, Ribot J, Duarte J, Agua-Doce A, Wollenberg I, Silva-Santos B, Graca L (2010). Identification of Regulatory Foxp3(+) Invariant NKT Cells Induced by TGF-beta. Journal of Immunology 185(4):2157-2163.
Lanca T, Correia D, Moita C, Raquel H, Neves-Costa A, Ferreira C, Ramalho J, Barata J, Moita L, Gomes A, Silva-Santos B. (2010). The MHC class Ib protein ULBP1 is a nonredundant determinant of leukemia/lymphoma susceptibility to gamma delta T-cell cytotoxicity. Blood. 115(12):2407-2411 .
Montero JA, Lorda-Diez CI, Certal AC, Moreno N, Rodriguez-Leon J, Torriglia A and Hurle JM (2010). Coordinated and sequential activation of neutral and acidic DNases during interdigital cell death in the embryonic limb. Apoptosis 15(10):1197-1210.
Larsen R, Gozzelino R, Jeney V, Tokaji L, Bozza FA, Japiassú AM, Bonaparte D, Cavalcante MM, Chora A, Ferreira A, Marguti I, Cardoso S, Sepúlveda N, Smith A and Soares MP. (2010). A central role for free heme in the pathogenesis of severe sepsis. Science Translational Medicine. 2(51):51ra71 (Press release).
IGC ANNUAL REPORT ‘10
PUBLICATIONS
Moura R, Weinmann P, Pereira P, Caetano-Lopes J, Canhão H, Sousa E, Mourão A, Rodrigues A, Queiroz M, Souto-Carneiro M, Graça L, Fonseca J. (2010). Alterations on peripheral blood B-cell subpopulations in very early arthritis patients. Rheumatology 49(6):1082-1092.
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Nagy E, Eaton JW, Jeney V, Soares, MP, Varga Z, Galajda Z, Szentmikloski J, Mehes G, Csonka T, Smith A, Vercellotti GM, Balla G, Balla J. (2010). Red Cells, Hemoglobin, Heme, Iron, and Atherogenesis. Arteriosclerosis Thrombosis and Vascular Biology 30(7):1347-U190.
Oteiza P, Koeppen M, Krieg M, Pulgar E, Farias C, Melo C, Preibisch S, Mueller D, Tada M, Hartel S, Heisenberg CP, Concha ML. (2010). Planar cell polarity signalling regulates cell adhesion properties in progenitors of the zebrafish laterality organ. Development 137(20):3459-3468. Otto EA, Hurd TW, Airik R, Chaki M, Zhou W, Stoetzel C, Patil SB, Levy S, Ghosh AK, Murga-Zamalloa CA, van Reeuwijk J, Letteboer SJ, Sang L, Giles RH, Liu Q, Coene KL, Estrada-Cuzcano A, Collin RW, McLaughlin HM, Held S, Kasanuki JM, Ramaswami G, Conte J, Lopez I, Washburn J, Macdonald J, Hu J, Yamashita Y, Maher ER, Guay-Woodford LM, Neumann HP, Obermüller N, Koenekoop RK, Bergmann C, Bei X, Lewis RA, Katsanis N, Lopes V, Williams DS, Lyons RH, Dang CV, Brito DA, Dias MB, Zhang X, Cavalcoli JD, Nürnberg G, Nürnberg P, Pierce EA, Jackson PK, Antignac C, Saunier S, Roepman R, Dollfus H, Khanna H, Hildebrandt F. (2010). Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nat Genet 42(10):840-50.
Naldi A, Carneiro J, Chaouiya C, Thieffry D. (2010). Diversity and plasticity of Th cell types predicted from regulatory network modelling. PLOS Computational Biology 6(9): e1000912. Nascimento R, Costa H, Dias JD, Parkhouse R. (2010). MHV-68 Open Reading Frame 20 is a nonessential gene delaying lung viral clearance. Archives of Virology 2010 Nov 23 [Epub ahead of print]. Neto-Silva RM, de Beco S, Johnston LA. (2010). Evidence for a growth-stabilizing regulatory feedback mechanism between Myc and Yorkie, the Drosophila homolog of Yap. Developmental Cell. 19(4):507-20. Nunes-Cabaco H, Ribot J, Caramalho I, Serra-Caetano A, Silva-Santos B, Sousa A. Foxp3 induction in human and murine thymus precedes the CD4(+) CD8(+) stage but requires early T-cell receptor expression. Immunology and Cell Biology 88(5):523-528.
FPavri R, Gazumyan A, Jankovic M, Di Virgilio M, Klein I, Ansarah-Sobrinho C, Resch W, Yamane A, San-Martin B, Barreto V, Nieland T, Root D, Casellas R, Nussenzweig M. (2010). Activation-Induced Cytidine Deaminase Targets DNA at Sites of RNA Polymerase II Stalling by Interaction with Spt5. Cell 143(1):122-133.
Oliveira NM, Hilker FM.(2010). Modelling disease introduction as biological control of invasive predators to preserve endangered prey. Bulletin of Mathematical Biology 72(2):444-68.
Pinto D, Pagnamenta A, Klei L, Anney R, Merico D, Regan R, Conroy J, Magalhaes T, Correia C, Abrahams BS, Almeida J, Bacchelli E, Bader G, Bailey A, Baird G, Battaglia A, Berney T, Bolshakova N, Boelte S, Bolton P, Bourgeron T, Brennan S, Brian J, Bryson S, Carson A, Casallo G, Casey J, Chung B, Cochrane L, Corsello C, Crawford E, Crossett A, Cytrynbaum C, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez B, Folstein S, Fombonne E, Freitag C, Gilbert J, Gillberg C, Glessner J, Goldberg J, Green A, Green J, Guter S, Hakonarson H, Heron, Elizabeth A, Hill M, Holt R, Howe J, Hughes G, Hus V, Igliozzi R, Kim C, Klauck S, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere C, Lamb J, Laskawiec M, Leboyer M, Le Couteur A, Leventhal B, Lionel A, Liu X, Lord C, Lotspeich L, Lund S, Maestrini E, Mahoney W, Mantoulan C, Marshall C, McConachie H, McDougle C, McGrath J, McMahon W., Merikangas A, Migita O, Minshew N, Mirza G, Munson J, Nelson S, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr J, Parrini B, Paton T, Pickles A, Pilorge M, Piven J, Ponting C, Posey D, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter M, Bierut L, Rice J, Salt J, Sansom K, Sato D, Segurado R, Sequeira A, Senman L, Shah N, Sheffield V, Soorya L, Sousa I, Stein O, Sykes N, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson A, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent J, Volkmar F, Wallace S, Wang K, Wang Z, Wassink T, Webber C, Weksberg R, Wing K, Wittemeyer K, Wood S, Wu J, Yaspan B, Zurawiecki D, Zwaigenbaum L, Buxbaum J, Cantor R, Cook E, Coon H, Cuccaro M, Devlin B, Ennis S, Gallagher L, Geschwind D, Gill M, Haines J, Hallmayer J, Miller J, Monaco P, Nurnberger J, Jr. P, Andrew D., Pericak-Vance, Margaret A., Schellenberg, Gerard D., Szatmari P, Vicente A, Vieland V, Wijsman E, Scherer S, Sutcliffe J, Betancur C. (2010). Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466 (7304):368-372.
Orge L, Oliveira A, Machado C, Lima C, Ochoa C, Silva J, Carvalho R, Tavares P, Almeida P, Ramos M, Pinto M, Simas J. (2010). Putative emergence of classical scrapie in a background of enzootic atypical scrapie. Journal of General Virology (91):1646-1650 Part 6. Ostrowski M, Carmo N, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume A, Freitas R, Goud B, Benaroch P, Hacohen N, Fukuda M, Desnos C, Seabra M, Darchen F, Amigorena S, Moita LF, Thery C.(2010). Rab27a and Rab27b control different steps of the exosome secretion pathway. Nature Cell Biology 12 (1):19-U61.
Pires AE, Afonso AF, Queirós A, Cabral MS, Porrata L, Markovic SN, Kaveri SV, da Silva MG, João C. (2010). Treatment With Polyclonal Immunoglobulin During T-cell Reconstitution Promotes Naive T-cell Proliferation. Journal of Immunotherapy 33(6):618-625. Pokorny I, Sharma R, Goyal S, Mishra S, Tiedemann R. (2010). MHC class I and MHC class II DRB gene variability in wild and captive Bengal tigers (Panthera tigris tigris). Immunogenetics 62(10):667-679. Quemere E, Champeau J, Besolo A, Rasolondraibe E, Rabarivola C, Crouau-Roy B and Chikhi L. (2010). Spatial Variation in Density and Total Size Estimates in Fragmented Primate Populations: The Golden-Crowned Sifaka (Propithecus tattersalli). American Journal of Primatology 72(1):72-80.
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Quemere E, Crouau-Roy B, Rabarivola C, Louis EE Jr and Chikhi L. (2010). Landscape genetics of an endangered lemur (Propithecus tattersalli) within its entire fragmented range. Molecular Ecology 19(8):1606-1621. Raposo BR, Rodrigues-Santos P, Carvalheiro H, Agua-Doce AM, Carvalho L, Pereira da Silva JA, Graça L, Souto-Carneiro MM. (2010). Monoclonal anti-CD8 therapy induces disease amelioration in the K/BxN mouse model of spontaneous chronic polyarthritis. Arthritis and Rheumatism 62(10):2953-2962.
Schlüter JP, Reinkensmeier J, Daschkey S, Evguenieva-Hackenberg E, Janssen S, Jänicke S, Becker JD, Giegerich R, Becker A. (2010). A genome-wide survey of sRNAs in the symbiotic nitrogen-fixing alpha-proteobacterium Sinorhizobium meliloti. BMC Genomics 11: 245. Schneider MV, Watson J, Attwood T, Rother K, Budd A, McDowall J, Via A, Fernandes P, Nyronen T, Blicher T, Jones P, Blatter MC, De Las Rivas J, Phillip Judge D, van der Gool W, Brooksbank C. (2010). Bioinformatics training: a review of challenges, actions and support requirements. Briefings in Bioinformatics 11(6):544-551.
Resende T, Ferreira M, Teillet M, Tavares A, Andrade R, Palmeirim I. (2010). Sonic hedgehog in temporal control of somite formation. Proceedings of the National Academy of Sciences of the United States of America. 107(29):12907-12912. Ribeiro C, Dickson BJ. (2010). Sex peptide receptor and neuronal TOR/ S6K signaling modulate nutrient balancing in Drosophila. Current Biology 20(11):1000-5 (Press release). Ribot J, Chaves-Ferreira M, d'Orey F, Wencker M, Goncalves-Sousa N, Decalf J, Simas J, Hayday A, Silva-Santos B. (2010). Cutting Edge: Adaptive Versus Innate Receptor Signals Selectively Control the Pool Sizes of Murine IFNgamma or IL-17-Producing gamma delta T Cells upon Infection. Journal of Immunology 185(11):6421-6425. Ros AFH, Lusa J, Meyer M, Soares MC, Oliveira RF, Brossard M, Bshary R (2010). Does access to the bluestreak cleaner wrasse Labroides dimidiatus affect indicators of stress and health in resident reef fishes in the Red Sea? Hormones and Behavior 2010 Nov 16 [Epub ahead of print].
Schneider N, Chikhi L, Currat M and Radespiel U. (2010). Signals of recent spatial expansions in the grey mouse lemur (Microcebus murinus). BMC Evolutionary Biology 10:105-121. Seixas C, Cruto T, Tavares A, Gaertig J, Soares H. (2010). CCTalpha and CCTdelta Chaperonin Subunits Are Essential and Required for Cilia Assembly and Maintenance in Tetrahymena. PLoS One 5(5):e10704. Sepúlveda N, Paulino CD, Carneiro J. (2010). Estimation of T-cell repertoire diversity and clonal size distribution by Poisson abundance models. Journal of Immunological Methods 353(1-2):124-137. Serpa J, Caiado F, Carvalho T, Torre C, Goncalves L, Casalou C, Lamosa P, Rodrigues M, Zhu Z, Lam E, Dias S. (2010). Butyrate-rich Colonic Microenvironment Is a Relevant Selection Factor for Metabolically Adapted Tumor Cells. Journal of Biological Chemistry 285(50):39211-39223. Shmelkov S, Hormigo A, Jing DQ, Proenca C, Bath K, Milde T, Shmelkov E, Kushner J, Baljevic M, Dincheva I, Murphy A, Valenzuela D, Gale N, Yancopoulos G, Ninan I, Lee F, Rafii S. (2010). Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive-like behaviors in mice. Nature Medicine 16(5):598-U135. Silva-Santos B. (2010). Promoting angiogenesis within the tumor microenvironment: The secret life of murine lymphoid IL-17-producing gammadelta T cells. European Journal of Immunology 40(7):1873-6.
Saenko S, Brakefield P, Beldade P. (2010). Single locus affects embryonic segment polarity and multiple aspects of an adult evolutionary novelty. BMC Biology 8. Article Number: 111. Salmona J, Dawson DA, Fouillot D, Ghestemme T, Thebaud T, Chikhi L, Salamolard M. (2010). The utility of existing passerine microsatellite markers for genetic studies in endangered species - as demonstrated for a critically endangered forest bird endemic to Réunion Island, the Réunion cuckooshrike (Coracina newtoni). Conservation Genetics Resources.
Soares MC, Bshary R, Fusani L, Goymann W, Hau M, Hirschenhauser K, Oliveira RF (2010). Hormonal mechanisms of cooperative behaviour. Philosophical Transactions of the Royal Society B-Biological Sciences 365(1553):2737-2750.
Sambo MR, Trovoada MJ, Benchimol C, Quinhentos V, Gonçalves L, Velosa R, Marques MI, Sepúlveda N, Clark TG, Mustafa S, Wagner O, Coutinho A and Penha-Gonçalves C. (2010). Transforming growth factor beta 2 and heme oxygenase 1 genes are risk factors for the cerebral malaria syndrome in Angolan children. PLos One 5(6):e11141 (Press release). Santos MR, Cosme AM, Becker JD, Medeiros JM, Mata MF, Moreira LM. (2010). Absence of functional TolC protein causes increased stress response gene expression in Sinorhizobium meliloti. BMC Microbiology 23; 10(1):180. Saraiva JL, Goncalves DM, Oliveira RF. (2010). Environmental modulation of androgen levels and secondary sex characters in two populations of the peacock blenny Salaria pavo. Hormones and Behavior 57(2):192-197.
Soares M. Cote I, Cardoso SC, Oliveira RF and Bshary R. (2010). Caribbean Cleaning Gobies Prefer Client Ectoparasites Over Mucus. Ethology 116(12):1244-1248. Sousa V, Penha F, Pala I, Chikhi L and Coelho MM. (2010). Conservation genetics of a critically endangered Iberian minnow: evidence of population decline and extirpations. Animal Conservation 13(2):162-171. Stollenwerk N, van Noort SP, Martins J, Aguiar M, Hilker FM, Pinto A, Gomes MGM. (2010). A spatially stochastic epidemic model with partial immunization shows in mean field approximation the reinfection threshold. Journal of Biological Dynamics 4:634-649.
Sardinha LR, Mosca T, Elias RM, do Nascimento RS, Goncalves LA, Bucci DZ, Marinho CR, Penha-Goncalves C, D'Imperio LMR and Alvarez JM (2010). The Liver Plays a Major Role in Clearance and Destruction of Blood Trypomastigotes in Trypanosoma cruzi Chronically Infected Mice. PLOS Neglected Tropical Diseases 4(1):e578. Santos ME, Athanasiadis A, Leitao AB, Dupasquier L, Sucena E. (2010). Alternative splicing and gene duplication in the evolution of the FoxP gene subfamily. Mol Biol Evol 28(1):237-47.
Tansey K, Brookes K, Hill M, Cochrane L, Gill M, Skuse D, Correia C, Vicente A, Kent L, Gallagher L, Anney R. (2010). Oxytocin receptor (OXTR) does not play a major role in the aetiology of autism: Genetic and molecular studies. Neuroscience Letters 474(3):163-167. Tavares R, Turer E, Liu C, Advincula R, Scapini P, Rhee L, Barrera J, Lowell C, Utz P, Malynn B, Ma A. (2010). The ubiquitin modifying enzyme A20 restricts B cell survival and prevents autoimmunity. Immunity 33(2):181-191.
Sato T, Rocancourt D, Marques L , Thorsteinsdottir S, Buckingham M. (2010). A Pax3/Dmrt2/Myf5 Regulatory Cascade Functions at the Onset of Myogenesis. PLOS GENETICS 6(4):e1000897.
IGC ANNUAL REPORT ‘10
PUBLICATIONS
Tenazinha N, Vinga S.(2010). “A Survey on Methods for Modeling and Analyzing Integrated Biological Networks”. IEEE/ACM Trans Comput Biol Bioinform [Epub ahead of print].
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Tolmachova T, Wavre-Shapton S, Barnard A, MacLaren R, Futter C, Seabra M. (2010). Retinal Pigment Epithelium Defects Accelerate Photoreceptor Degeneration in Cell Type-Specific Knockout Mouse Models of Choroideremia. Investigative Ophthalmology & Visual Science 51 (10):4913-4920. Thornhill JA., McVeigh P., Jurberg AD., Kusel JR. (2010). Pathways for the influx of molecules into cercariae of Schistosoma mansoni during skin penetration. Parasitology 137(7):1089-1098.
Sepúlveda N, Carneiro J. (2010) Repertoire dynamics of peripheral regulatory and effector T cells competing for antigen presenting cells. In: Current Mathematical Models in T cell Biology Lythe and Molina-Paris (Eds). Elsevier. In press. Yin HH, Costa R. (2010) Striatal dopamine and glutamate in action: the generation and modification of adaptive behavior. Frontiers in Neuroscience, The Role of Dopamine in the Basal Ganglia, ed. Susan Jones. Taylor & Francis Group, Boca Raton, FL, US.
Trindade S, Perfeito L, Gordo I. (2010). Rate and effects of spontaneous mutations that affect fitness in mutator Escherichia coli. Philosophical Transactions of the Royal Society B: Biological Sciences 365(1544):1177-86. Van Noort SP, Nunes MC, Weedall GD, Hviid L and Gomes MG. (2010). Immune selection and within-host competition can structure the repertoire of variant surface antigens in Plasmodium falciparum - a mathematical model. PLoS One 5(3):e9778.
BOOK REVIEW Padovan E. (2010) Book review: Diagnostic samples: From the patient to the Laboratory by Walter G. Guder, Sheshadri Narayanan, Hermann Wisser and Bernd Zawta, Wiley-Blackwell Ed., ISBN: 978-3-527-32307-4. Eur. J. Immunol 40: 922.
Vasale JJ, Gu WF, Thivierge C, Batista PJ, Claycomb JM, Youngman EM, Duchaine TF, Mello CC, Conte D. (2010). Sequential rounds of RNA-dependent RNA transcription drive endogenous small-RNA biogenesis in the ERGO-1/Argonaute pathway. Proceedings of the National Academy of Sciences of the United States of America 107(8):3582-3587
OTHER PUBLICATIONS
Venkatraman S, Jin X, Costa R, Carmena JM. (2010). Investigating Neural Correlates of Behavior in Freely Behaving Rodents Using Inertial Sensors. Journal of Neurophysiology 104(1):569-575.
Prado A, Cristina D, Bubela T. (2010). Setting up a technology transfer office for a life sciences research institute in a european economy: opportunities and challenges. Tomorrow’s Technology Tranfer 2(1):38-45.
Ferrer E, González LM, Gárate T, Parkhouse RM. (2010) Cisticercosis: una enfermedad tropical abandonada. La lucha frente a las enfermedades de la pobreza: responsabilidad y necesidad, Fundación BBVA.
Viana D, Gordo I, Sucena E, Moita MAP. (2010). Cognitive and Motivational Requirements for the Emergence of Cooperation in a Rat Social Game. PLOS ONE 5(1):Article Number: e8483. Vinagre T, Moncaut N, Carapuço M, Névoa A, Bom J and Mallo M. (2010). Evidence for a myotomal Hox/Myf cascade governing nonautonomous control of rib specification within global vertebral domains. Developmental Cell 18(4):655-661 (Press release). Zelenay S, Bergman M, Sousa Paiva R, Lino A, Martins A, Duarte J, MoraesFontes M, Bilate A, Lafaille J, Demengeot J. (2010). Cutting edge: Intrathymic Differentiation of Adaptative Foxp3+Regulatory T Cells upon Peripheral Proinflammatory Immunization. Journal of Immunology 185(7):3829-33. Zhao Y, Yan A, Feijo J, Furutani M, Takenawa T, Hwang I, Fu Y, Yang Z. (2010). Phosphoinositides Regulate Clathrin-Dependent Endocytosis at the Tip of Pollen Tubes in Arabidopsis and Tobacco. The Plant Cell 22:4031-4044 BOOK CHAPTERS Cabrito TR, Remy E, Teixeira MC, Duque P, Sá-Correia I. (2010) Resistance to herbicides in the model organisms Saccharomyces cerevisiae and Arabidopsis thaliana: the involvement of multidrug resistance transporters. Herbicides, Theory and Applications (ed. Nikolic A), IN-TECH Publishers, Vienna, Austria. Chaouiya C, Klaudel H, Pommereau F. (2010) A Modular, Qualitative Modeling of Regulatory Networks Using Petri Nets. Modeling in Systems Biology, the Petri Net Approach. Koch I, Reisig W, Schreiber F (Eds.), Springer. Gordo I and Sousa A. (2010) Mutation, Selection and Genetic Interactions in Bacteria. In: Encyclopedia of Life Sciences. Prado MP, Feijó JA, Porterfield MD (2010) Calcium dependent NO signaling in plant cell polarity and sexual reproduction. Nitric Oxide in Plant Physiology. S. Hayat, M. Mori, J. Pichtel, and I. Ahmad (eds.) WILEY-VCH Verlag GmbH & Co. KGaA, Weinheimin. pp. 31-50.
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AWARDS AND HONOURS INSTITUTO GULBENKIAN DE CIÊNCIA Best Places to Work for Post-docs 2010 Award The Scientist - Faculty of 1000's Magazine of the Life Sciences
Mónica Bettencourt Dias Nominated Associate Editor of Molecular Biology of the Cell (American Society for Cell Biology)
Rui Costa Seeds of Science - Life Science Award Ciência Hoje and Ciência Viva (Portugal)
Carlos Penha-Gonçalves Nominated Academic Editor on the Editorial Board of PLosOne (Public Library of Science)
Tânia Vinagre, Natalia Moncaut, Marta Carapuço, Ana Nóvoa, Joana Bom and Moises Mallo 2010 Pfizer Prize for Basic Research Sociedade das Ciências Medicas de Lisboa and Pfizer Laboratories (Portugal)
Patrícia Beldade Invited to join the Editorial Board of EvoDevo (BioMedCentral) Jorge Carneiro Invited to join the Editorial Board of BioSystems (Elsevier)
Rosário Sambo and Carlos Penha Gonçalves 2010 Pfizer Prize for Clinical Research Sociedade das Ciências Medicas de Lisboa and Pfizer Laboratories (Portugal)
Gabriela Gomes Invited to join the editorial board of the Journal of Statistical Communications in Infectious Diseases (Berkeley Electronic Press) Moises Mallo Invited to join the Editorial Board of Developmental Dynamics (Wiley) Miguel Seabra Invited to join the Editorial Board of Biochemical Journal (Portland Press Limited)
Miguel Seabra Member of the Wellcome Trust Molecules, Genes and Cells Funding Panel
Rui Oliveira Member of the Programme Committee of the Annual Meetings of the Society for Behavioural Neuroendocrinology (USA)
Alaa Abi-Haidar and Luis Rocha "Biomedical Article Classification Using an Agent-Based Model of T-Cell Cross-Regulation" Best Paper Award 9th International Conference on Artificial Immune Systems David Cristina (IGC), Luis Graça (IMM) and Marta Monteiro (IMM) Acellera Therapeutics National BES Innovation Competition - Health Technologies Category Award Banco Espírito Santo, Portugal David Cristina (IGC), Luis Graça (IMM) and Marta Monteiro (IMM) Acellera Therapeutics ANJE Young Entrepreneur Award Associação Nacional de Jovens Empresários, Portugal
Zachary Mainen Elected member of the European Molecular Biology Organisation (EMBO) Isabel Gordo Elected member of the Council of the European Society for Evolutionary Biology Miguel Seabra Member of External Advisory Board of IBILI, Univ. Coimbra Miguel Seabra Awarded the Jessie Mole Lectureship, Oxford University
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BREAKDOWN OF IGC EXPENDITURE 2010 TOTAL: €17.1m PERSONNEL (STAFF AND RESEARCHERS)
€7.54m INFRASTRUCTURE (BUILDING MAINTENANCE AND REFURBISHMENTS)
€1.9m OPERATIONS (NEW EQUIPMENT, FACILITIES COSTS, ETC)
€7.7m CALOUSTE GULBENKIAN FOUNDATION (CORE)
€5.1m EXTERNAL (FUNDING AGENCIES, OTHERS)
€6m
IGC FUNDING SOURCES 2010 CALOUSTE GULBENKIAN FOUNDATION (CORE)
€5.1m EXTERNAL PRIVATE (CHAMPALIMAUD FOUNDATION, COMPANIES, OTHERS))
€5.2m EXTERNAL PUBLIC (EUROPEAN COMMISSION, FCT, CITY COUNCILS)
€6.8m
COMPETITIVE RESEARCH GRANTS RUNNING AT THE IGC IN 2010 TOTAL: 145 (includes new grants awarded in 2010)
FUNDAÇÃO PARA A CIÊNCIA E TECNOLOGIA
ASSOCIAÇÃO VIVER A CIÊNCIA + CRIOESTAMINAL
93
2
EUROPEAN COMMISSION (EU)
BILL & MELINDA GATES FOUNDATION
26
1
EMBO + FCT + FCG
ASSOCIAÇÃO PARA O DESENVOLVIMENTO FCUP
3 CÂMARA MUNICIPAL DE OEIRAS
1
3
ADVANCEMENT OF RESEARCH FOR MYOPATHIES, USA
FUNDAÇÃO BIAL
1
3
APCL - ASSOCIAÇÃO PORTUGUESA CONTRA A LEUCEMIA
EMBO
1
2 HFSP
AUTISM SPEAKS, CONSORTIUM USA, UK, CANADA AND IRELAND AGENCIES
2
1
EMBAIXADA DO CANADÁ E NRS-LPCC
FUNDAÇÃO LUSO AMERICANA
2
1
RESEARCH GRANTS RUNNING AT THE IGC 2010 BY NATIONALITY OF FUNDER NATIONAL
106 EUROPEAN
30 INTERNATIONAL
5 PARTNERSHIP
4
IGC ANNUAL REPORT ‘10
MAJOR FUNDING SOURCES
106
GRADUATE TRAINING AND EDUCATION
MAJOR FUNDING SOURCES
PHD PROGRAMME IN INTEGRATIVE BIOMEDICAL SCIENCES Head: Thiago Carvalho
Within Cells 11 - 15 October Lars Jansen (IGC, Portugal) (Org) Mónica Dias, Miguel Godinho, Catarina Henriques, José Leal (IGC), Jagesh Shah (USA), Minoo Rassoulzadegan (FR), Robin Allshire (UK)
PhD in Immunology
The PhD Programme in Integrative Biomedical Sciences (PIBS) offers graduate students the opportunity to learn and discuss cutting edge topics and fundamental concepts in biological sciences, before they choose a theme for their thesis work.
SUPPORT STAFF Manuela Cordeiro (Administrative Assistant) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal Calouste Gulbenkian Foundation, Portugal
The PIBS programme is supported by the Fundação Para Ciência e Tecnologia and the Calouste Gulbenkian Foundation. The programme selects a small number of students to develop their own research projects at the IGC. PIBS students are chosen by a committee from a large pool of applicants from all over the world, with very diverse backgrounds, not restricted to life sciences. After a semester of courses taught by a mixture of IGC faculty and invited guest lecturers, students are given time to design their research programmes. PIBS students are strongly encouraged to engage in projects that involve more than one research group at the IGC.
Genetic Models 25-29 October Vitor Barbosa (IGC, Portugal) (Org) Vitor Barbosa, Miguel Ferreira, Elena Baena, Moises Mallo, Thiago Carvalho (IGC), Caryn Navarro (USA), Fernando Roch (FR), Karen Liu (UK), Mathieu Molet (FR) Evolution (Population Genetics) 1-5 November Isabel Gordo (IGC, Portugal) (Org) Isabel Gordo, Ana Margarida Sousa, Ivo Chelo, Patrícia Brito (IGC), Guillaume Martin (FR), Lilia Perfeito (DE)
Student life at the IGC is a learning experience not restricted to the course modules, with several workshops and courses available throughout the year, an abundance of guest seminar speakers (who are asked to spend time with graduate students), as well as meetings students themselves organise, like their annual retreat. PIBS is the continuation of a strong investment in graduate education at the IGC that dates back to 1993. IGC alumni as a group have not only been personally sucessful, over the past decade those who stayed or returned to Portugal have dramatically reshaped the country’s research landscape.
Evolution (Evolution and Development) 8-12 November Patrícia Beldade (IGC, Portugal) (Org) Patrícia Beldade, Christen Mirth, Élio Sucena (IGC), Michael Akam (UK), Christian Braendle (FR), Johannes Jaeger (ES) Instrumentation 15-19 November Nuno Moreno (IGC, Portugal) (Org) Nuno Moreno (IGC), Simon Monard (UK), Jan Willem Borst (NL)
STUDENTS IN 2010 Cláudia Mendes Ewa Anna Chrostek Jorge André Sousa Krzysztof Kuś Leonor Duarte Madalena Carneiro Marc Gouw Ozlem Aybuke Isik Jordi Salmona
Between Cells 8-22 October António Jacinto (IMM, Portugal) (Org) António Jacinto (IMM/IGC), Soren Prag, Leonor Saude, Rita Fior, Susana Lopes (IMM), Florence Janody, Catarina Certal, Joaquin Leon (IGC), Karina Xavier (ITQB/IGC), Christos Zervas, Vassiliki Kostourou (GR)
Immunology 22-26 November Luis Teixeira (IGC, Portugal) (Org) LuisTeixeira,ThiagoCarvalho,VascoBarrero,MiguelSoares(IGC),BrunoSantos(IMM), Jonathan Howard (DE), Louis Du Pasquier (CH), Santiago Zelenay (UK)
Portuguese Biology Polish Biotechnology Portuguese Informatics Engineering Polish Biotechnology Portuguese Pharmacy Portuguese Chemical Engineering Dutch Life Science and Technology Turkish Molecular Biology French Plant Biotechnology
Hypothesis Driven Research 29 November - 10 December Rui Martinho and Vasco Barreto (IGC, Portugal) (Org) Rui Martinho, Alekos Athanasiadis, Vasco Barreto, (IGC), Manuel Santos (UA-PT), Donald Rio, Michael Lynch, Nina Papavasiliou (USA)
MODULES RUN IN 2010 Arrival and orientation week 13 - 17 September Thiago Carvalho and Zach Mainen (IGC) (Org) Rita Venturini, Paul Bush (USA) History of Biology 20 - 24 September Thiago Carvalho (IGC, Portugal) (Org) Lars Jansen, Christen Mirth, Anthony Dean, Alekos Athanasiadis, Monica Dias, José Leal, Joe Paton (IGC), Fern Elsdon-Baker (UK), Jonathan Howard (DE) Statistics 27 September - 8 October Jorge Carneiro (IGC, Portugal) (Org) Jorge Carneiro (IGC)
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PHD PROGRAMME IN COMPUTATIONAL BIOLOGY
INDP - INTERNATIONAL NEUROSCIENCE DOCTORAL PROGRAMME
Director: Jorge Carneiro
Director: Zachary Mainen
Group Leader - Quantitative Organism Biology Group
Group Leader - Systems Neuroscience Group and Head of Champalimaud Neruoscience Programme at the IGC
The PhD Programme in Computational Biology (PDBC) is a pilot graduate programme that aims to create a critical mass of researchers in computational biology, who will act as the future leaders in the field. To this end it operates in close association with its twin initiative, the Collaboratorium in Computational Biology. It is promoted by the Portuguese Ministry for Science and Technology, the Calouste Gulbenkian Foundation, and Siemens Portugal SA. The PDBC was launched in 2005, has a definitive lifespan and was planned to educate four generations of 12 students per year. Education is organised as a four-year programme divided into a year of full-time courses, workshops and projects, covering the main aspects of computational biology from the biological, computational, mathematical, chemical and physical points of view, and three years of research training in a recognised laboratory anywhere in the world, including Portugal. Non-national citizens were accepted but their research training was restricted to Portuguese research labs. The choice of laboratory was left to the student but met the standards set by the Programme Direction.
SUPPORT STAFF Cláudio Soares (ITQB, Deputy Director) Manuela Cordeiro (Administrative Assistant) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal Siemens Portugal, SA Calouste Gulbenkain Foundation, Portugal PT Foundation, Portugal Fundação Luso-Americana para o Desenvolvimento (FLAD), Portugal Fundação para a Computação Científica Nacional (FCCN), Portugal
The International Neuroscience Doctoral Programme (INDP) aims to train students to perform innovative and integrative research into the biological bases of behaviour. During the first year, students attend courses organised by a combination of internal faculty and invited international researchers. This initial training phase aims at providing students with a broad background and common language in biology and neuroscience. The curriculum emphasises active participation, discussion and practical exercises. The goal is to develop critical and creative thought and to gain exposure to a variety of perspectives on the biology of the nervous system.
SUPPORT STAFF Élio Sucena (Coordinator) Alexandra Piedade (Assistant) FUNDING Champalimaud Foundation, Portugal Fundação para a Ciência e a Tecnologia (FCT), Portugal Calouste Gulbenkian Foundation, Portugal
Autumn courses, organised in conjunction with the in-house PIBS programme, focus on general biological principles. Spring courses concentrate on neuroscience,including physiology, development, sensory and motor systems, learning, social behaviour and cognition. There is a strong quantitative component to the curriculum, including programming, data analysis and modeling. At the end of the first year, students choose a thesis laboratory guided by faculty, the programme director and neuroscience core faculty. In 2010, the INDP entered its fourth year. A total of 40 students were enrolled, including 8 first-year students, 12 students performing thesis research abroad and 20 developing their research in CNP laboratories at the IGC.
The PDBC has come of age and all 41 students are carrying out their research training in labs in Europe and beyond, and three (Pedro Monteiro, Bruno Correia, and Luis Figueiredo) have obtained their doctoral degree. Information on the individual students can be found in our website (link ‘students’), where visitors can find also their completed theses.
STUDENTS IN 2010 Bruno Miranda Ana Carolina de Sousa Gustavo Mello Gonçalo Lopes Ivo Marcelo Raimundo Coelho Leong Tiago Marques Simone Lackner
Portuguese MD Portuguese Biotechnology Brazilian Psychology/Psychobiology Portuguese Computer Science Portuguese Biological engineering Portuguese Mathematics Portuguese Physics/engineering Austrian Molecular Biology
MODULES RUN IN 2010 Core concepts I 11 - 16 January Rui Costa (CNP-IGC), Susana Lima (CNP-IGC), Marta Moita (CNP-IGC) Core concepts II 18 to 23 January Rui Costa (CNP-IGC), Susana Lima (CNP-IGC), Marta Moita (CNP-IGC) Evolution & Development I 25 - 30 January Luisa Vasconcelos (CNP-IGC) (Org) Joshua Corbin (George Washington University) Evolution & Development II 1 - 6 February Luisa Vasconcelos (CNP-IGC) (Org) Chris Braun (Hunter college), Georg Striedter (University of California at Irvine) Cellular physiology 8 - 13 February Joe Paton (CNP-IGC) (Org) Kevin Franks (Columbia), Josh Dudman (HHMI, JFRC), Guillaume Dugue (CNP-IGC)
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PROGRAMME FOR ADVANCED MEDICAL RESEARCH DOCTORAL PROGRAMME FOR PHYSICIANS Director: Leonor Parreira
Learning & Plasticity I 22 - 27 February Marta Moita (CNP-IGC) and Inbal Israely (CNP-IGC) (Org) Martha Constantine-Paton (MIT), Steven Kushner (Erasmus Medical Center, Rotterdam)
Histology and Developmental Biology Faculdade de Medicina da Universidade de Lisboa, Portugal
Learning & Plasticity II 1 - 6 March Marta Moita (CNP-IGC) and Inbal Israely (CNP-IGC) (Org) Allan Hobson (Harvard Medical School), Richard Morris (University of Edinburgh), Bruno da Silva (University of Edinburgh)
The Programme for Advanced Medical Education is a Doctoral Programmme for physicians, supported by the Gulbenkian (FCG) and Champalimaud Foundation (FC), the Ministry of Health and the Fundação para a Ciência e a Tecnologia (FCT), Portugal.
Metabolism 8 - 13 March Carlos Ribeiro (CNP-IGC) (Org) Leon Avery (Univeristy of Texas, Southwestern)
FUNDING Ministry of Health, Portugal Fundação para a Ciência e a Tecnologia (FCT), Portugal Calouste Gulbenkian Foundation, Portugal Champalimaud Foudnation, Portugal
The Programme is targeted at highly motivated clinicians who, as a complement to their clinical practice, wish to acquire a strong scientific background as a basis for excellence in medical research and clinical practice. The programme selects 10 students per year, five on a full time-basis (Specialists and Interns), fully supported by a FCG or FC three year fellowship, five on a part-time basis (Interns). Part-time students receive a six months FCG fellowship for full-time attendance of graduate courses, after which they return to the internship supported by FCT and the Ministry of Health.
Foraging 15 - 20 March Carlos Ribeiro (CNP-IGC) and Rui Costa (CNP-IGC) (Org) Action 22 - 27 March Rui Costa (CNP-IGC) (Org) Jose Carmena (University of California at Berkeley); Joseph McIntyre (Université Paris Descartes); Chris de Zeeuw Erasmus University)
Students receive six months' graduate courses by an international Faculty, followed by doctoral thesis work at national or international institutions. Graduate courses take place at leading Portuguese biomedical research institutions: Instituto Gulbenkian de Ciência; Instituto de Medicina Molecular/ Faculdade de Medicina de Lisboa; IPATIMUP, Porto; Faculdade de Ciência Médicas, Universidade Nova de Lisboa; Faculdade de Medicina da Universidade do Porto.
Social behaviour 1 – 7 April Susana Lima (CNP-IGC) and Zach Mainen (CNP-IGC) (Org) Ken Harris (Imperial College) and Marta Moita (CNP-IGC)
STUDENTS IN 2010
Sense and Systems 12 - 17 April Joe Paton (CNP-IGC), Brian Lau (Columbia) and Kenway Louie (NYU) (Org) David Freedman (U. Chicago), Anitha Pasupathy (U. Washington)
FULL-TIME:
Eva Pereira Mendes Ana Sadio Assunção Tuna Luis Rocha Lopes Jorge Ruivo
Attention and Cognition 19 - 24 April Joe Paton (CNP-IGC), Leo Sugrue (Stanford), and Greg Corrado (Stanford/IBM) (Org) Michael Goldberg (Columbia), Kacy Ballard (Stanford)
Intern in Radiology, Hospital Fernando Fonseca, Lisbon Specialist in Gastroenterology, Hospital da Guarda, Guarda Specialist in Neurology, Hospital Santo António, Porto Specialist in Cardiology, Hospital Garcia de Orta, Almada Intern in Internal Medicine, Hospital Santa Maria, Lisbon
PART-TIME:
The Basics of Experimental Neuroscience 26 April - 1 May Zach Mainen (CNP-IGC) (Org) Adam Kampff (CNP-IGC), Florian Engert (Harvard), Bence Ölveczky (Harvard), Rajesh Poddar (Harvard)
Ana Rita Matos Dulce Alfaiate Joaquim P. Silva Patrícia Reis Ricardo R. Pinto
Techniques: Imaging, Ethology & Physiology 3 - 8 May Zach Mainen (CNP-IGC) (Org) Adam Kampff (CNP-IGC), Florian Engert (Harvard), Bence Ölveczky (Harvard), Rajesh Poddar (Harvard), Mike Orger (Harvard)
MODULES RUN IN 2010 Opening Lecture 1 October Leonor Parreira (IGC, Portugal) (Org) Erna Möller (Karolinska Institutet, Sweden), Cecília Naucler (Karolinska Institutet, Sweden)
Imaging projects 10 - 15 May Zach Mainen (CNP-IGC) (Org) Adam Kampff (CNP-IGC), Brian Keeley (Pitzer College)
Gene Expression 2-15 October João Ferreira (IMM/FML, Portugal) (Org) João Ferreira (IMM / FML), Luis F. Moita (IMM / FML), Margarida G Carvalho (FML, BioFig-FCUL), Carlos Farinha (FCUL), Francisco Enguita (IMM / FML), Joana Cardoso (IMM), Jamal Tazi (Institut de Génètique Molèculaire, Montpellier), Patrick Varga-Weisz (Babraham Institute, Cambridge), Christian Muchardt (Institut Pasteur, Paris)
Bayesian Brain 17 - 22 May Zach Mainen (CNP-IGC) (Org) Alex Pouget (University of Rochester) and Jeff Beck (UCL, Gatsby)
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Intern in Thoracic Surgery, Hospital Pulido Valente, Lisbon Intern in Infecciology, Hospital Egas Moniz, Lisbon Intern in Pshychiatry, Hopsital S. Francisco Xavier, Lisbon Intern in Pediatrics, Hospital Santa Maria, Lisbon Intern in Orthopedics, Hospital Santo António, Porto
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GTPB - THE GULBENKIAN TRAINING PROGRAMME IN BIOINFORMATICS Director: Pedro Fernandes
Structural Biology 18-22 October José Pereira Leal (IGC, Portugal) (Org) José Pereira-Leal (IGC), Guillermo Montoya (CNIO), Francisco Enguita (IMM), Claudio Gomes (ITQB/UNL), Nuno Palma (BIAL), Alekos Athanasiadis (IGC), Maria Luisa Rodrigues (IGC), Bruno Victor (TQB/UNL) Cell Cycle, Cytoskeleton & Disease 25-29 October Mónica Bettencourt Dias (IGC, Portugal) (Org) Buzz Baum (UCLA, UK), Ted Weinert (Arizona University, USA), Helder Maiato (IBMC), Carla Martins (Cancer Research, UK), Andrew Jackson (MRC, UK), Peter Jackson (Genentech, California, USA), Monica Bettencourt Dias (Centrosomes & Cell Cycle, IGC) , Miguel Godinho Ferreira (Telomeres and Genome Stability, IGC), Florence Janody (ctin Cytoskeleton & Cancer, IGC), Lars Jansen (Centromeres & Epigenetics, IGC), Rui Martinho (Early Fly Development, IGC), Vitor Barbosa (Meiosis & Development, IGC)
The GTPB has been running at the IGC since 1999. It aims at providing a fair degree of independence in the usage of Bioinformatics tools and resources. This is achieved by combining a series of methods that maximise the rate of acquisition of skills, while keeping the attendees interested in the conceptual framework of each course theme. The courses are exclusively taught in English, and completely documented in electronic form (CDROM; DVD). Tracking of self-assessment questionnaires allows for a continued improvement in the organisation and methods. Periodical polling for expressions of interest allows probing new subjects for adequacy to the interests of audiences that are constantly being renewed. GTPB courses range very widely in level, from introductory to professionally specialised. The programme's design features are described in the paper Pedro L. Fernandes, "The GTPB training programme in Portugal", Brief Bioinform, first published online October 21, 2010.
Medical Statistics 1-6 November Armando Teixeira Pinto (FMUP, Portugal) (Org) Armando Teixeira Pinto (FM.UP), Jaroslaw Harezlak (Univ. Indiana, USA) Computational Biology 8-12 November José Pereira Leal (IGC, Portugal) (Org) Patrick Aloy (Institute for Biomedical Research, ES), Nuria Lopez-Bigas (University Pompeu Fabra, ES), James Brenton (Cancer Research, UK), Sofia Braga (IGC), Ana Teresa Maia ( Cancer Research, UK), Isabel Gordo (IGC), Jorge Carneiro (IGC), Ana Teresa Freitas (INESC-ID/IGC), Ramana Madupu (J. Craig Venter Institute, USA), Yu-Hui Rogers (J. Craig Venter Institute, USA), José PereiraLeal (IGC)
In 2010, a total of 223 students attended the GTPB training programme: 131 from the Oeiras Associated Laboratory (IGC, ITQB and IBET), and 92 from external research institutes. Of these, 51 were Portuguese, and 38 were foreigners. COURSES RUN IN 2010 All courses were organised by Pedro Fernandes. Molecular Evolution, Phylogenetics and Adaptation 15 - 19 February Hernan Dopazo, François Serra
Epidemiology 15-19 November Isabel dos Santos Silva (London School of Hygiene and Tropical Medicine, UK) (Org) Valerie McCormack (International Agency for Research on Cancer, Lyon, FR), Pablo Perel (London School of Hygiene and Tropical Medicine, UK), Isabel dos Santos Silva (London School of Hygiene and Tropical Medicine, UK)
Introductory Bioinformatics (First Course) 8 - 12 March David Judge, Phil Cunningham, Pedro Fernandes Bioinformatics using Python for Biologists 19 - 23 April Allegra Via, Mariagiovanna Mazzapioda
Genetics 22-26 November Carlos Penha Gonçalves (IGC, Portugal) (Org) Taane Clark (Wellcome Trust Sanger Institute, Hinxton, UK), Susana Campino (Wellcome Trust Sanger Institute, Hinxton, UK), Lounes Chicki (IGC), Frank Dudbridge (London School of Hygiene and Tropical Medicine, UK), Thomas Dan Otto (Wellcome Trust Sanger Institute, Hinxton, UK), Isabel Marques (IGC), Carlos Penha-Gonçalves (IGC)
Hunting for genes and promoters 3 - 6 May Alexander Kel, Enrique Blanco Microarray Data Analysis using GEPAS and Babelomics 10 - 12 May Joaquin Dopazo, Javier Santoyo-Lopez, Ana Conesa Automatic Functional Annotation and Data Mining 13 - 14 May Ana Conesa, Javier Santoyo-Lopez
Participants in the Bioinformatics using Python for Biologists course.
Macromolecular NMR assignment with CcpNmr Analysis 31 May - 4 June Manolis Matzapetakis, Pedro Lamosa, Rasmus Fogh, Tim Stevens, Marc van Dijk Analysis and manipulation of phylogenomic data using ETE 23 - 25 June Jaime Huerta-Cepas, Marina Marcet-Houben RNA Bioinformatics 5 - 7 July Paul Gardner, Anton Enright Proteomics data analysis wihtin the GTPB Programme
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THESES MSc THESES
Microarray Data Analysis using R and Bioconductor 6 - 10 September Nuno Barbosa-Morais, Oscar Rueda, Benilton Carvalho
Pedro Alves Arousal and its effect on hormonal response. Instituto Superior de Psicologia Aplicada, Portugal February 2010
Proteomics Data Analysis 13 - 17 September Lennart Martens, Lukas Käll
Aubin Besolo Estimation de la densitédu Propithecus tattersalli (Simons, 1988) au nord-est, du Propithecus coquereli (Grandidier, 1867) et Propithecus coronatus (Edwards, 1871) au nord-ouest de Madagascar. University of Mahajanga, Madagascar July 2010
Structural Genomics and Drug Design 20 - 24 September Marc Marti-Renom, Antonio Pineda-Lucena Pathway Analysis and Drug Targets 18 - 20 October Alexander Kell, Alexey Zakharov, Roman Zubarev
Niccolò Bonacchi Behavioral suppression in a modified conflict paradigm - A framework to test the photostimulation of 5-H. Instituto Superior de Psicologia Aplicada, Portugal. February 2010
Integrative Cancer Genomics 8 - 10 November Nuria Lopez-Bigas, Gunes Gundem Biostatistical Foundation in Bioinformatics 15 - 18 November Lisete Sousa, Carina Silva
Paulo Duarte Fission yeast as a test tube for assembling complex biological structures. Escola Superior Agrária de Bragança, Portugal November 2010
Introductory Bioinformatics (Second Course) 20 November - 6 December David Judge, Phil Cunningham, Pedro Fernandes
Rita Félix The relationship of ERG Potassium Channel with programmed cell death in the vertebrate developing limb. Universidade de Lisboa, Portugal November 2010 Fernando Ferreira Regeneração da barbatana caudal em peixe-zebra (Danio rerio): uma perspectiva biofísica (Regeneration of the caudal fin in zebrafish (Danio rerio): a biophysical perspective). Universidade de Lisboa, Portugal December 2010 Maria Gallo Genome-wide analysis of telomere protection in S. pombe. Universidad Complutense de Madrid, Spain September 2010 Maria Adelina Jerónimo Wound response and pigmentation pattern formation. Universidade de Lisboa, Portugal November 2010 Ana Carina Marcelino Global and local effects on pigmentation in Bicyclus anynana butterflies. Universidade de Lisboa November 2010 Nuno Martins Different behaviours elicited by CO2 in fruit fly larvae. Universidade de Lisboa, Portugal. December 2010 Sofia Melo Relationship between perceived stress and cortisol response during an academic exam. Instituto Superior de Psicologia Aplicada, Portugal December 2010 Patrícia Mendonça Effects of mood manipulation on testosterone and cortisol. Instituto Superior de Psicologia Aplicada, Portugal February 2010
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SEMINARS WORKSHOPS AND MEETINGS
Pedro Prudêncio Differential requirements of αPKC activity within different epithelial tissues. Universidade do Algarve, Portugal March 2010 Emmanuel Rasolondraibe Distribution spatiale des ressources alimentaires chez Propithecus tattersalli (SIMONS, 1988), P. coquereli (GRANDIDIER, 1867) et P. coronatus (MILNE EDWARDS, 1871) ainsi que certains aspects de sa distribution. University of Mahajanga, Madagascar July 2010 Joana Ferreira da Silva Winners and Losers: social modulation of behaviour in zebrafish (Danio rerio). Instituto Superior de Psicologia Aplicada, Portugal February 2010 Sofia Soares Optogentic identification of striatal cell types during timing behavior. Universidade Nova de Lisboa, Portugal December 2010 Ines Tenente The role of telomerase in cell proliferation in zebrafish (Danio rerio). Universidade de Lisboa, Portugal November 2010 PhD THESES Teresa Fagundes Mating system of the peacock blenny at Ria Formosa: male alternative mating tactics and sex-role reversal. Universidade do Porto, Portugal October 2010 Leonor Galhardo Fish welfare: behavioural, cognitive and physiological aspects in the Mozambique tilapia, Oreochromis mossambicus. Universidade do Porto, Portugal. July 2010 Filipa Pontes de Moraes Tbx1 and Bmp2 in the development of the ear, neural crest and pharyngeal system in mice. Universidade Nova de Lisboa, Portugal March 2010 Lisa Roque Emotional regulation, temperament, attachment and adrenocortical functioning in children. Instituto Superior de Psicologia Aplicada, Portugal November 2010 Zita Santos Evolution and biogenesis of microtubule-derived structures. Universidade Nova de Lisboa, Portugal November 2010 Vitor Sousa Inference of admixture and population size changes in structured populations with applications to conservation genetics. Universidade de Lisboa, Portugal. March 2010
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SEMINARS AT THE IGC JANUARY 2010
MARCH 2010
DATE SPEAKER AFFILIATION TITLE
DATE SPEAKER AFFILIATION TITLE
05.01
Carlos Penha-Gonçalves
IGC
Pregnancy-associated malaria in the mouse
02.03 Moises Mallo IGC Body building... beyond muscles
08.01
Domingos Henrique
Instituto de Medicina Molecular, Lisboa
Welcome to Notchland
05.03 Richard Morris University of Edinburgh, UK Memory Consolidation: Synaptic Tagging and Schemas
12.01
Miguel Godinho Ferreira
IGC
Telomeres and chromosome-end protection
15.01
Karel Svoboda
Howard Hughes Medical Institute
The neural circuits underlying somatosensation
19.01 Rui Costa IGC Generating and Sequencing Actions 22.01 Charles Zuker
Columbia University College of Physicians and Surgeons, Howard Hughes Medical Institute
From the Tongue to the Brain: The Biology of Mammalian Taste
26.01 Elisabetta Padovan IGC Blood monocytes: desguised regulators of T cell responses 27.01 Bill Hansson Dep. Evolutionary Neuroethology, Evolution of Olfaction Max Planck Institute for Chemical Ecology, Germany 29.01 Andres Alcover Institut Pasteur, France Immunological synapses and their subversion by HIV-1 and HTLV-1 retroviruses
09.03 Miguel Soares IGC Towards a molecular basis of host tolerance to infection 11.03 Leon Avery University of Texas Southwestern Medical Center, Behavioral Strategies in C elegans Dallas, Texas 12.03 John F. X. Diffley Cancer Research UK London Research Institute Mechanism and Regulation of DNA Replication during the Cell Cycle and in Response to DNA Damage 12.03 EU Project Management 16.03 José Leal IGC The bacteria within 23.03
João Sousa
IGC
ITI - Past, present and future
23.03 Rosalina Fonseca IGC Shaping the system: rules of heterosynaptic plasticity 25.03 Dinu Florin Albeanu Cold Spring Harbor Laboratory Understanding neuronal circuits in the mammalian olfactory bulb
FEBRUARY 2010 DATE SPEAKER AFFILIATION TITLE 02.02 Jorge Carneiro IGC Getting there by running round in circles: the sensorimotor system of a single (sperm) cell
26.03 Tom Silhavy Princeton University Outer Membrane Biogenesis in Gram-Negative Bacteria 30.03
Jorg Becker
IGC
When boy meets girl… beyond DNA and diamonds
05.02 Octávio Mateus Universidade Nova de Lisboa (CICEGe-FCT) Paleontology of Jurassic dinosaurs of Portugal & Museu da Lourinhã. evolutionary perspective 09.02
Rob Kesseler
IGC
Morphogenesis: hybrid fusions of art and science.
APRIL 2010 DATE SPEAKER AFFILIATION TITLE
12.02 Mark Travis University of Manchester, Faculty of Life Sciences, UK Keeping the immune system in check: the role of dendritic cells, integrins and TGF-beta in preventing autoimmunity and fighting infection 15.02 Alexander Friedman Multidisciplinary Brain Research Center Behavioral “re-programming” through pattern Bar-Ilan University, Israel stimulation of the neuronal tissue 19.02 Angela Gallo Ospedale Pediatrico Bambino Gesù, Rome RNA editing A-to-I: from RNA modification to human pathology 23.02 Robert Horvitz MIT, USA The Genetic Control of Programmed Cell Death in C. elegans 26.02 Jocelyne Demengeot IGC Thymic Tricks and Treats 26.02 Ana Confraria Centre for Research in Agrogenomics, Barcelona A role for brassinosteroids and auxin in the vascular patterning of the Arabidopsis stem
07.04
Andrew Poulos
UCLA
Pathways to Fear, Memory & Trauma
09.04 Ji He The Samuel Roberts Noble Foundation, Ardmore Novel Machine Learning Architectures for Knowledge Discovery from Heterogeneous Data Domains and Their Applications to Functional Genomics 12.04
David Glover
University of Cambridge, UK
Centrosome Assembly and Function
13.04 Jorg Becker IGC Genomics and Gene Expression units and Carlos Penha Gonçalves 20.04 Alekos Athanasiadis IGC Principles of Protein Nucleic Acids Interactions: Unmasking the Biological Function of Z-DNA 23.04 Michael Goldberg Columbia University Hering and Helmholtz were both right: two mechanisms for spatial accuracy in the parietal cortex 27.04 Robert Malinow Dep. of Neurosciences and Biology, Synapses in normal and diseased brain function Univ. of California at San Diego 30.04
Mónica Dias
IGC
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Centriole and Cilia Biogenesis and Evolution
MAY 2010
JUNE 2010
DATE SPEAKER AFFILIATION TITLE
DATE SPEAKER AFFILIATION TITLE
03.05 Catherine Nguyen TAGC - U928, Inserm, Université de la Méditerranée Integrative analyses of transcriptional regulatory networks involved in diseases and immune responses
04.06 Guido Barbujani Univ Ferrar Human genome diversity: frequently asked questions
03.05 Dave Lovinger National Institutes of Health (NIAAA/NIH) Synaptic Plasticity in Striatum: Substrates for Action Learning?
07.06 Gohta Goshima Nagoya University Mechanisms of microtubule nucleation and growth in cells
04.05 Enrique Blanco Departament de Genetica/IBUB, Wing imaginal disc regeneration Universitat de Barcelona
08.06 Marie Louise Bergman IGC TEC it for granted: New mechanism used by Thymic Epithelial Cells to promote tolerance
04.05 Rui Martinho IGC Constraints on gene expression during early embryonic development
08.06 Sílvia Castro IGC Science communication through the media (the old and the new)
05.05 Cristina Marquez Dep de Psicobiologia i Metodologia de les Ciencies de la Salut, Univ Autònoma de Barcelona Mad, Bad or Sad? Neural correlates of abnormal aggression following peripubertal stress in rats
08.06 Jeremy Reiter UCSF, USA Primary cilia regulate Hedgehog signaling in development and cancer
06.05 Rainer Friedrich Friedrich Miescher Institute Neuronal circuits and computations in the olfactory system 07.05 Christian Peeters Laboratoire Ecologie & Evolution, Université Pierre Social buffering and the repeated evolution et Marie Curie, Paris of wingless reproductives in ants 11.05 Manuel Rebelo IGC The Animal House Facility at IGC and Moisés Mallo
08.06 Tamara Caspary Emory University School of Medicine, Atlanta Normal neural tube patterning without maintained graded Shh activity 11.06 Kamal Sen Dept. of Biomedical Engineering, Boston University Neural discrimination of complex natural sounds in songbirds 14.06 Sebastian Amigorena Curie Institute, Paris, France T cell-Dendritic Cell dynamics during priming and tolerance
14.05 Eurico Sá Cambridge University Molecular mechanisms for organization of cell polarity and axis formation in Drosophila
15.06 Michael Parkhouse IGC Pathogen Host Evasion Mechanisms: Ready made tools for the control of infectious and non-infectious diseases
14.05
15.06
Manuel A. S. Santos
Department of Biology - CESAM, University of Aveiro
The engineering of a genetic code alteration
18.05 Gerald Schatten University of Pittsburgh School of Medicine Centrosome Challenges During Fertilization and In Pluripotent Stem Cells 18.05
Constantin Fesel
IGC
Lupus, autoantibodies and T-cell regulation
21.05
Antony Carr
University of Sussex
Mechanisms of genome stability
27.05 Sheila Vidal IGC How to apply to 2010 FCT Call for individual fellowship 28.05 Don Cleveland Ludwig Institute, LaJolla USA Guarding the genome: centromeres, aneuploidy and tumorigenesis
University of Magdeberg, Magdeberg, Germany
Neutrophils at work: in vivo, full color, and real time
16.06 Laura Johnston Columbia University, College of Physicians Mechanisms of growth regulation and Surgeons in the Drosophila wing 16.06 Michael Dustin New York University Top down and bottom up approaches to T cell activation 17.06
25.05 Gabriela Gomes IGC Ecology and evolution of infectious diseases: The case of influenza
Matthias Gunzer
Ulrich von Andrian
Harvard University Medical School
In vivo visualization of T cell priming in lymph nodes
17.06 Catia Laranjeira National Institute for Medical Research, London In vivo identification of neural stem cells in the enteric nervous system National 18.06 Andrew Bowie School of Biochemistry and Immunology, Virus-host interactions and pattern recognition Trinity College Dublin receptor signalling 22.06 Karina Xavier IGC Interference with inter-species bacterial cell-cell communication 24.06
Andrew Murray
University of Harvard
How budding yeast cells find a mate
25.06 Carsten Janke Curie Institute, Paris Tubulin modifying enzymes as regulators of microtubule functions 28.06 Patrick Meraldi ETH biochemistry, Zurich Finding the middle ground: achieving the perfect metaphase plate 28.06 Sandrinne Etienne-Manneville Pasteur Institute Mechanisms of centrosome positioning in migrating cells 28.06 Catarina Carmo The Janus kinase TYK2 mediates FGF-2-induced chemoresistance 28.06
Monica Gotta
University of Geneva
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Asymmetric cell division in C. elegans
JULY 2010
AUGUST 2010
DATE SPEAKER AFFILIATION TITLE
DATE SPEAKER AFFILIATION TITLE
02.07 Nic Tapon London Research Institute Developmental control of tissue size by the Hippo signalling pathway
04.08
09.07 Francesco Colucci University of Cambridge School of Clinical Medicine New views on natural killer cells in reproduction and cancer
12.07 Ekaterina Vinnik Hippocampal representation of sound-guided behavior 13.07 Carlos Ribeiro IGC The neuronal and molecular control of food choice in Drosophila 14.07 Vincenzo Bronte Ist. Oncologico Veneto and Venetian Inst. Tumor-induced tolerance and immune suppression for Molecular Medicine, Padova, Italy depend on C/EBPb transcription factor 15.07 Kohtaro Tanaka Shriners Research Center, Portland, Oregon Molecular and morphogenetic mechanisms underlying evolution of sex combs in Drosophila species 16.07 Luisa Figueiredo Instituto de Medicina Molecular The role of chromatin in antigenic variation of African Trypanosomes 20.07 Miguel Seabra IGC Membrane Traffic and Disease 21.07 Samuel Aparício University of British Columbia Genetic heterogeneity in cancer revealed by next generation genome sequencing 23.07 Stefan Thor Dep. of Clinical and Experimental Medicine From Progenitor to Unique Neuron: Linkoping Univ., Sweden Cell Specification by the Integration of Temporal and Positional Cues 23.07 Arp Schnittger Inst. de Biologie Moléculaire des Plantes du CNRS, Plant reproductive biology Univ. de Strasbourg 26.07 Antonella Viola Humanitas Research Institute, Rozzano, Italy Signaling amplification at the T cell immunological synapse
New York University School of Medicine
Natural and Adaptive Regulatory T Cells
09.08 Andrew Seeds Janelia Farm Research Campus, HHMI Neurons affecting innate grooming behavior in Drosophila 09.08
12.07 Pavle Itskov Texture coding in rat brain: From the neuronal code for roughness in the barrel cortex to persistent and independent traces of stimulus and reward location in hippocampus
Juan Lafaille
Arnim Jenett
Janelia Farm Research Campus, HHMI
Not supplied
10.08 Keith Gull University of Oxford, UK Centrioles and basal bodies: conservation and diversity in evolution and biological functions 12.08 Adam Peltan University of York Drosophila RNAi screen to identify host factors regulating phagocytosis of Leishmania parasites
SEPTEMBER 2010 DATE SPEAKER AFFILIATION TITLE 03.09 John Kearney University of Alabama, Birmingham Modulation of Allergy and Autoimmunity by Perinatal Exposure to Specific Microorganisms 03.09 Neil Perkins Newcastle University Regulation of cancer cell proliferation and survival by NF-kappaB 07.09 Lounes Chikhi IGC Is DNA mytho-chondrial? (some results on the Neolithic transition in Europe) 08.09 Michael Schroeder Biotec and Dept. of Computing, Dresden Network compression: Concept and Applications in Neurodegeneration and Cancer 09.09 Benilton Carvalho University of Cambridge Improvements on preprocessing of massive microarray datasets 10.09 Acaimo González-Reyes Univ. Pablo de Olavide, Sevilla Extracellular matrix and signalling in a stem cell niche: A view from Drosophila. 10.09 Oscar Rueda University of Cambridge Copy number analysis of 1001 breast cancer tumors: METABRIC project 14.09
Ana Domingos
Rockefeller University
Leptin Regulates the Hedonic Value of Sucrose
14.09
Lennart Martens
University of Ghent
Protein quantification: a question of data processing
27.07 Luís Rosário IGC Regulation of Cardiac Progenitor Cells Proliferation and Differentiation by microRNAs
16.09 Lukas Käll Stockholm University Semi-supervised machine learning for the peptide identification problem in shotgun proteomics
27.07 Ivo Chelo IGC Dynamics of adaptation from standing genetic variation in Drosophila melanogaster experimental populations
17.09 Siegfried Roth Institut für Entwicklungsbiologie,Universität The evolution of gene regulatory networks zu Köln, Biowissenschaftliches Zentrum, Germany for dorsoventral patterning in insects 21.09 Lars Jansen IGC Vertebrate molecular genetics is coming of age: Cool tools to understand centromeres
30.07
António Jacinto
Instituto de Medicina Molecular
The Actin Wave
23.09 Snjezana Juric Not supplied Connecting The Dots: Implementation Of The Novel Thylakoid Protein Trol Into The Z-Scheme 23.09 Marc Marti-Renom Centro de Investigación Príncipe Felipe, Three-dimensional folding of chromosomal Valencia, Spain domains in relation to gene expression 24.09 João Barata Instituto de Medicina Molecular PTEN non-deleting posttranslational inactivation in human T-cell leukemia 28.09 Vasco Barreto IGC Clonal Analysis of V(D)J rearrangement in immunoglobulin genes: implications for allelic exclusion of the Ig loci and beyond 30.09 Laszlo Tirian Institute of Molecular Pathology (IMP) Toward understanding the genetic control of male courtship behaviour in Drosophila
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IGC ANNUAL REPORT ‘10
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125
OCTOBER 2010 DATE SPEAKER AFFILIATION TITLE
DATE SPEAKER AFFILIATION TITLE
01.10 Erna Moller Karolinska Institute Translational medical research - what is it really about?
25.10 Caryn Navarro Boston University School of Medicine Genetic and Molecular Analysis of Cell Polarity and the piRNA Pathway
06.10 Estelle Remy IGC A novel Major Facilitator Superfamily transporter in Arabidopsis: A component of the auxin transport system?
25.10 Kenn Albrecht Boston University School of Medicine Genetic and genomic analysis of mammalian gonadal progenitor differentiation 26.10
06.10 Matteo de Rosa IGC Structural characterization of protein: nucleic acid complexes 07.10 Ernst H. K. Stelzer EMBL-Heidelberg Light sheet-based fluorescence microscopy (LSFM) reduces phototoxic effects and provides new means for the modern life sciences 11.10 Jagesh Shah Harvard Medical School Spindle Checkpoint Dynamics - Achieving Tight Inhibition and Rapid Release 12.10 Isabel Campos Instituto de Medicina Molecular Embryonic epithelia wound healing: a genetic approach in Drosophila 12.10 Bruno Correia PhD Program in Computational Biology, Computational Design of Epitope-scaffolds: Portugal and Washington Univ., Seattle, USA rational strategies for epitope transplantation and antibody re-elicitation 13.10 Rui Sanches Universidade do Algarve Teachers 13.10 Armand Leroi Imperial College London The Metabolic Logic of Growth and Ageing in Worms 13.10 Dan Needleman Harvard Medical School Spindle Assembly, Architecture & Evolution: From Laser Ablation to Microtubule Nucleation
Elena Baena
IGC
Energy signals in the plant stress response
27.10 Catarina Cortesão IGC Ectopic expression of Activation-Induced Cytidine Deaminase (AID) 27.10 Ted Weinert University of Arizona Repeats, Dicentrics and Genome Instability: Lessons from Yeast 28.10
Andrew Jackson
MRC, Edinburgh
Cellular Pathways determining brain size
28.10 Karen Liu Dept of Craniofacial Development, GSK-3 at the crossroads: King's College London chemical tools and embryonic signaling 29.10 Peter Jackson Genentech How The Cell Smells: Organizing Signaling within Primary Cilia
NOVEMBER 2010 DATE SPEAKER AFFILIATION TITLE 02.11 Carla Lopes University of Leicester Satellites and Antennae: cellular studies on the OFD1 disease protein
14.10
Martin Raff
University College London
An Outsider's Take on Autism
02.11 Henrique Teotónio IGC Adaptation from standing genetic variation in C. elegans
14.10
Minoo Rassoulzadegan
Inserm, Université de Nice, France
RNA mediated epigenetic heredity in mice
03.11 Mariana Faria IGC Not supplied
15.10 Robin Allshire Making Wellcome Trust, Edinburgh CENs of Heterochromatin: rebooting and programming centromeres 15.10
Maria Mota
Instituto de Medicina Molecular
Plasmodium - Host - Plasmodium Interactions
03.11 Catarina A. Pereira IGC Not supplied 04.11 Hauke Drechsler University of Heidelberg Cortical regulation of astral microtubule function in yeast
18.10 Paul Martin University of Bristol Epigenetics and immune cell recruitment - parallels between wound repair and cancer
05.11 Michael Laessig University of Cologne Independence and interference of molecular functions
18.10
09.11 Gaelle Marteil Université de Rennes Study of M phase regulation in Xenopus laevis oocytes
Christos Zervas
Biomedical Research Foundation, Academy of Athens
Adhesion in Drosophila Development
19.10 Florence Janody IGC The interplay between the actin cytoskeleton and signal transduction pathways. 20.10
Nádia Duarte
IGC
Role of B1 cells in early steps of type 1 diabetes
20.10
Leonardo Guilgur
IGC
aPKC function "beyond apical-basal polarity
21.10 Sidonia Fagarasan
Lab Mucosal Immunity Riken, Research center Allergy Immunoglobulin A, Vitamine A and gut homeostasis and Immunology, Yokohama City, Kanagawa, Japan
21.10 Ben Engel UCSF IFT Train Size: Implications for Flagellar Length Control 22.10 Vassiliki Kostourou Alexander Fleming Biomedical Sciences Research Center 25.10 Buzz Baum UCL
Vascular Development in Health and Disease
09.11 Élio Sucena IGC Evolution and Development of Arthropod Innate Immunity 10.11 Philip Gerrish Centro de Matemática e Aplicações Fundamentais, Genomic mutation rates that cause extinction: Univ. de Lisboa general evolutionary predictions 10.11 Américo Rodrigues IGC SnRK1.1 Protein interactors 10.11 Cecile Vanpe IGC Genetic effects of habitat loss and fragmentation on lemurs from Northern Madagascar: an integrative approach 10.11 Christian Frezza The Beatson Institute for Cancer Research, Glasgow Starve cancer to death: metabolic synthetic lethality as a new strategy for cancer therapy
Cell shape through the cell cycle 11.11
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Michael Akam
University of Cambridge
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The evolution of segmentation in animals
DECEMBER 2010 DATE SPEAKER AFFILIATION TITLE
DATE SPEAKER AFFILIATION TITLE
12.11 Wallace Marshall UCSF The flagellar length control system - A paradigm for organelle size control
02.12 Pierre Crozet Université Paris-Sud 11 Study of the upstream regulation of Arabidopsis SnRK1
16.11 António Coutinho IGC Old Amateur's Concerns
03.12
17.11 Elodie Mohr IGC Help for immunoglobulin production: myeloid cells, CD4, CD8 T cells and a hint of regulatory T cells?
07.12 Bruno Cardoso Instituto de Medicina Molecular TAL1/SCL is down-regulated upon HDAC inhibition in T-cell Acute Lymphoblastic Leukemia cells
17.11 Ivo Chelo IGC Dynamics of adaptation from standing genetic variation in Drosophila melanogaster experimental populations: behind the scenes 18.11 Josh Corbin George Washington University Embryonic patterning mechanisms for constructing the mammalian limbic system 19.11 Niels Gehring University of Cologne Post-transcriptional control of gene expression: exon junction complexes and beyond 22.11 Stéphane Marcand Commissariat à l'énergie atomique, Fontenay Dicentric breakage at telomere fusions 23.11 Lúcia Marri Supramolecular complexes in redox signalling: a case study about an intrinsically disordered protein, CP12, regulating photosynthetic enzymes 23.11 Christen Mirth IGC Size Control and Feeding Behaviour: the development and evolution of environmentally dependent traits 24.11 Sabine Patot IGC Symbiotic protection against viruses in Drosophila melanogaster 24.11 Luís Valente IGC Centromeres: genetic or epigenetic? 26.11 Louis du Pasquier Basel University Origin and evolution of the vertebrate leukocyte receptors: the lesson from tunicates 29.11 Kathrin Steck Max Planck Institute for Chemical Ecology in Jena Smells like home: Olfactory orientation in desert ants
Paula Duque
IGC
07.12 Rui Oliveira IGC Swimming in Vygotsky pool: Social modulation of hormones, brain and behavior 09.12 Nina Papavasiliou The Rockefeller University Genome Diversification: DNA breaks and antigenic variation in T. brucei 09.12 Ivo G. Gut Centro Nacional de Análisis Genómico (CNAG) From Genome-Wide Association To Whole Genome Barcelona Sequencing 09.12 Paulo Vieira Institut Pasteur Specification and commitment during differentiation of B lymphocytes 10.12
Michael Lynch
Indiana University Bloomington
Mutation and Evolution
10.12
Averil Ma
University of Chicago
Ubiquitination and Innate Immunity
14.12
Isabel Gordo
IGC
The geometry of adaptation in E. coli
15.12 Lisa Bergman IGC Ruled by the thymus: Immunity vs. tolerance to foreign antigens 15.12 Rasmus Larsen IGC A Central Role for Free Heme in The Pathogenesis of Severe Sepsis 17.12 Raquel Oliveira Dep. Biochemistry, University of Oxford The Ring Cycle: building and breaking chromosome linkages 21.12 Ana Raquel Tomás IGC Apical Ectodermal Ridge Activity during limb development
30.11 Donald Rio UC Berkeley Mechanisms of P element transposition and alternative pre-mRNA splicing in Drosophila
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A role for SR proteins in plant stress responses
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PRESENTATIONS BY IGC RESEARCHERS
The Role of small RNAs During Germ Cell Specification in Arabidopsis Pollen XXI International Congress on Sexual Plant Reproduction Bristol, UK August 2010
RICARDO ÁGUAS Prospects for malaria eradication in sub saharan Africa Jornadas de Epidemiologia Teórica Centro Internacional de Matemática Coimbra, Portugal January 2010
PATRÍCIA BELDADE Evolutionary diversification and evo-devo of butterfly wing-patterns Laboratory of Entomology Wageningen University The Netherlands February 2010
Applicability of simple deterministic models in epidemiologically complex scenarios Workshop on Dynamical Systems Applied to Biology and Natural Sciences Universidade de Lisboa Lisbon, Portugal February 2010
Evo-devo: the mechanisms behind morphological diversification ISEM, University of Montpellier France June 2010
Applicability of simple deterministic models in epidemiologically complex scenarios Oxford University February 2010
Pulling butterfly wings: genes and environment in evolutionary diversification EuroScience Open Forum (ESOF) 2010; Symposium on The challenges of a changing environment: How do animals cope? Lingotto Conference and Exhibition Center Torino, Italy July 2010
RITA AIRES Dynamic extracellular proton fluxes during fin regeneration in Zebrafish Joint Meeting of the Portuguese and Spanish Developmental Biology Societies Badajoz, Spain November 2010
Evo-devo and the mechanisms behind morphological diversification Department of Zoology & Animal Biology University of Geneva Switzerland September 2010
ANA TERESA AVELAR Contribution of chromosomal rearrangements for Adaptation and Speciation Faculdade de Ciências e Tecnologia Universidade Nova de Lisboa, Portugal October 2010
LAURA NAPAL BELMONTE Drosophila, a model to study neuronal nutrient sensing pathways and how they control feeding behaviour 14th Portuguese Obesity Conference Porto, Portugal November 2010
ELENA BAENA-GONZÁLEZ Convergent stress and energy signaling EMBO Young Investigator Meeting Heidelberg, Germany May 2010 Convergent stress and energy signaling Instituto Superior de Agronomia (ISA) Lisbon, Portugal June 2010
MÓNICA BETTENCOURT-DIAS Keystone Meeting on Cilia and Human Disease Monterrey, California, USA February 2010 Sloan Kettering Institute New York, USA February 2010
Energy signaling events in the convergent stress response 6th SPPS PhD Student Conference Helsinki, Finland September 2010
Curie Developmental Biology Institute Paris, France June 2010 Biozentrum Basel, Switzerland June 2010
VASCO BARRETO Functional analysis of the AID from a cartilaginous fish AID Workshop Stockholm, Sweden June 2010 A clonal analysis of V(D)J rearrangement in immunoglobulin genes Implications for allelic exclusion Instituto de Medicina Molecular Lisbon, Portugal November 2010
Young Investigator PhD Course, EMBO Heidelberg, Germany September 2010 Institut de Génétique et Dévelopement de Rennes Université de Rennes France September 2010 EMBC meeting, EMBO Heidelberg, Germany November 2010
JÖRG BECKER The Role of miRNAs During Germ Cell Specification in Arabidopsis Pollen XVII Congress of the Federation of European Societies of Plant Biology Valencia, Spain July 2010
IGC ANNUAL REPORT ‘10
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IGC ANNUAL REPORT ‘10
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131
Centrosome Conference Baeza, Spain November 2010 ASCB meeting Philadelphia, USA December 2010
Heterogeneity of Breast Cancer Dia da Engenharia Biomédica, Escola Superior de Tecnologia de Setubal Setubal, Portugal November 2010 Heterogeneity of Breast Cancer Faslodex Annual Meeting Figueira da Foz, Portugal November 2010
Pittsburgh, USA December 2010
PATRÍCIA BRITO Incongruência entre genealogias e filogenias Instituto Superior de Agronomia (ISA) Universidade Técnica de Lisboa Lisbon, Portugal November 2010
LEONOR BOAVIDA Identification and Characterization of Gamete-Expressed Proteins with Potential Fusogenic Roles during Double Fertilization XXI International Congress on Sexual Plant Reproduction Bristol, UK August 2010 A Potential Role of Tetraspanins in Sexual Reproduction in Plants 4th European Conference on Tetraspanins Birmingham, UK September 2010
JORGE CARNEIRO How to tame a transposon. Lesson from a stochastic Petri net model of V(D) J recombination University of Utrecht Utrecht, The Netherlands March 2010
MARIE BONNET Quantitative Biology of Illegitimate DNA Rearrangements in Lymphocytes Annual meeting of the Sociedade Portuguese de Immunologia Braga, Portugal September 2010
Why aren't Petri nets widely used in biological research? BioPPN, International Workshop on Biological Processes & Petri Nets Satellite Event of Petri Nets 2010 Braga, Portugal June 2010
FILIPE BORGES Silencing and Epigenetic Control During Germ Cell Reprogramming in Arabidopsis Pollen 6th Course on Epigenetics Paris, France March 2010
Insights into sea urchin spermatozoa chemotaxis provided by morphodynamic models Systems Biology Symposium International Institute for Physics, Federal University of Rio Grande do Sul Natal, Brazil July 2010
The Role of miRNAs During Germ Cell Specification in Arabidopsis Pollen XXXV Jornadas Portuguesas de Genética Braga, Portugal June 2010
Getting there by running round in circles: the sensorimotor system of a single (sperm) cell Instituto de Biotecnología Universidad Nacional Autónoma de Mèxico Cuernavaca, México September 2010
The Role of miRNAs During Germ Cell Specification in Arabidopsis Pollen 21st International Conference of Arabidopsis Research Yokohama, Japan June 2010
Multiscale modelling approach to immunological tolerance University of Leeds Leeds, UK November 2010
MicroRNA Activity in the Arabidopsis Male Germline Cold Spring Harbor Laboratory USA December 2010
SOFIA CARVALHO Inbreeding and outbreeding life-history effects in C. elegans Caenorhabditis elegans Evolution Meeting Hinxton/UK May 2010
SOFIA BRAGA Are all aromatase inhibitors created equal? European Breast Cancer Conference Barcelona, Spain March 2010
Inbreeding and outbreeding life-history effects in C. elegans Portuguese Evolution Meeting Lisbon, Portugal December 2010
Heterogeneity of Breast Cancer S. Paulo School of Translational Science S. Paulo, Brazil April 2010
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IGC ANNUAL REPORT ‘10
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133
Claudine Chaouiya Logical models provide insights into regulatory networks dynamics 4th International Workshop on Practical Applications of Computational Biology and Bioinformatics Guimarães, Portugal June 2010
Porto Ciência Porto, Portugal June 2010 EMCCS Summer School Venice, Italy October 2010
Reduction of logical models of regulatory networks yields insight into dynamical properties IEEE International Conference on Control Applications Yokohama, Japan September 2010
JOCELYNE DEMENGEOT Mouse models of primary Immunodeficiencies São Paulo Advanced School on Primary Immunodeficiencies: Unraveling Human Immuno-Physiology Brazil November 2010
Goals and challenges in developing a computational modelling framework for cellular regulatory networks First International Conference On Basic & Applied Sciences (ICBAS) Gaza, Palestine October 2010
PAULA DUQUE Alternative splicing and proteomic diversity in plant stress response Workshop on Biodiversity Facing Environmental Changes Aveiro, Portugal April 10
IVO CHELO The population genetics of reverse evolution in Drosophila Portuguese Evolution Meeting Lisbon, Portugal December 2010
Plant SR proteins and their functions in abiotic stress response Instituto de Medicina Molecular Lisbon, Portugal December 2010
SÍLVIA CORREIA African Swine Fever Virus (ASFV) has evolved multiple strategies to evade IFN responses Cytokines in Infectious Diseases, Autoimmune Disorders and Cancer Chicago, USA October 2010
ADRIEN FAURÉ Dorsal patterning of the Drosophila eggshell IGC Post-doc Meeting Oeiras, Portugal October 2010
CATARINA CORTESÃO Ectopic Expression of Activation Induced Cytidine Deaminase IGC Post-doc Meeting October 2010
Modularity in biological regulatory networks Yamaguchi University Japan December 2010
Ectopic Expression of Activation Induced Cytidine Deaminase IGC Practical Course on Image Acquisition in Immunology June 2010
Modelling the dorsal patterning of the Drosophila egg DrosTuga, IGC Oeiras, Portugal December 2010
RUI COSTA Conference Reward and Decision Making in the Brain Jerusalem, Israel February 2010
JOSÉ FEIJÓ Of ion choreography and the regulation of apical cell growth: molecular partners and integrative theoretical models Imaging, phenotyping and modelling plant organ morphogenesis Agropolis Foundation (Plenary Speaker) Montpellier, France March 2010
Winter Plasticity Meeting, Aruba February 2010 AC Camargo Hospital São Paulo, Brazil April 2010
Of ion choreography and the regulation of apical cell growth: molecular partners and integrative theoretical models. John Ines Research Institute Norwich, UK May 2010
University of Maryland Medical School Baltimore, MD, USA April 2010 Institut du Fer à Moulin Paris, France May 2010
Of ion choreography and the regulation of apical cell growth: molecular partners and integrative theoretical models FESPB, Universit of Valencia (Plenary Speaker) Spain July 2010
Neuroethics Conference Fundação Calouste Gulbenkian and French Embassy Lisbon, Portugal May 2010
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IGC ANNUAL REPORT ‘10
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Of ion choreography and the regulation of apical cell growth: molecular partners and integrative theoretical models IASPR, University of Bristol (Plenary Speaker) UK August 2010
GABRIELA GOMES Integrative epidemiology Workshop on Theoretical Epidemiology, International Centre for Mathematics Coimbra, Portugal January 2010
Of ion choreography and the regulation of apical cell growth: molecular partners and integrative theoretical models. GARNet 2010 Meeting - Cells and Systems (Plenary Speaker) Durham, UK September 2010
Perspectives in integrative epidemiology Instituto de Biologia Molecular e Celular Porto, Portugal January 2010 Perspectives in integrative epidemiology Workshop on Dynamical Systems Applied to Biology and Natural Sciences Universidade de Lisboa, Portugal February 2010
Of ion choreography and the regulation of apical cell growth: molecular partners and integrative theoretical models 15th International Workshop on Plant Membrane Biology (Plenary Speaker) Adelaide, Australia September 2010
Monitoring and modeling influenza epidemics Instituto de Higiene e Medicina Tropical Lisboa, Portugal May 2010
RITA FÉLIX Erg activity triggers interdigital cell death during digit development Joint Meeting of the Portuguese and Spanish Developmental Biology Societies, Badajoz, Spain November 2010
Epidemiology and evolution of infectious diseases: The case of influenza III Conference on Computational and Mathematical Population Dynamics, Bordeaux 2 University France June 2010
LISETE FERNANDES From yeast oxidative stress response to tumor and drug resistance Faculdade de Ciências Médicas Universidade Nova de Lisboa Lisbon, Portugal March 2010
Ecology and evolution of infectious diseases: The case of influenza Fundação Oswaldo Cruz Rio de Janeiro, Brazil August 2010 Shifting priorities in the mathematics of infectious diseases Instituto de Matemática Pura e Aplicada Rio de Janeiro, Brazil October 2010
INÊS FERREIRA EMBO Workshop: Chromossome segregation and aneuploidy Scotland, UK June 2010
ISABEL GORDO Experimental evolution in Escherichia coli CMAF, Faculdade de Ciências da Universidade de Lisboa Lisbon, Portugal February 2010
ANA GODINHO Myth-busting through dialogue and debate Euroscience Open Forum (ESOF 2010) Turin July 2010
Adaptation in E. Coli Gameets Meeting Curia, Portugal December 2010
Round-table panelist: Science Communication and Dissemination Panel ANICT National Symposium Lisbon, Portugal May 2010
FLORENCE JANODY The actin cytoskeleton: a tumor suppressor organelle Instituto de Medicina Molecular Lisbon, Portugal April 2010
MIGUEL GODINHO FERREIRA How telomeres escape checkpoint surveillance in fission yeast University of Geneva, Sciences III Geneva, Switzerland June 2010
LARS JANSEN Epigenetics Natural History museum (British Council) Maputo Mozambique March 2010
Telomeres avoid chromosome-end detection by severing the checkpoint signal transduction pathway EMBO Telomere meeting Marseille, France September 2010
The centromere: a showcase for epigenetic inheritance Wellcome Trust Edinburg, UK August 2010
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IGC ANNUAL REPORT ‘10
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The many virtues of SNAP-tagging BRIK Copenhagen, Denmark September 2010
MAGOR LORINCZ Temporal framing of thalamic relay-mode firing by phasic inhibition during the alpha rhythm FENS Amsterdam, The Netherlands July 2010
Can Proteins be heritable? II Jornadas de Bioengenharia Porto, Portugal November 2010
PEDRO MACHADO Drosophila Portuguese Annual Meeting Portugal December 2010
ROBERTO KELLER Flapping wings and strong heads: novel thorax architectures in queen and worker ants XVI Congress of the International Union for the Study of Social Insects, Copenhagen, Denmark. August 2010
ZACHARY MAINEN Neural codes and computations underlying odor-guided decisions in the rat Brain Circuits Workshop Ein Gedi, Israel February 2010
KAI KONRAD CDK's activate plasma membrane ion channels 15th International Workshop on Plant Membrane Biology (Selected abstract) Adelaide, Australia September 2010
Neural codes and computations underlying odor-guided decisions in the rat Weizmann Institute Rechovot, Israel February 2010 Targeting the 5-HT system using optogenetics: Towards a post-pharmacological view Cosyne Workshops Snowbird, Utah, USA March 2010
TAKASHI KOYAMA Seeking a missing link: how does insulin signaling regulate ecdysone signaling? 18th International Ecdysone Workshop Ceske Budejovice, Czech Republic July 2010
Neural mechanisms underlying odor-guided decisions in the rat Cosyne Workshops Snowbird, Utah, USA March 2010
Exploring the potential role for FoxO in integrating insulin and ecdysone signaling to control body size DrosTuga 2010 Oeiras, Portugal December 2010
Neural codes and computations underlying odor-guided decisions in the rat: Uncertainty in brain and behavior Tamagawa-Caltech Lecture Course on Decision-Making Tamagawa University Tokyo, Japan March 2010
JOSÉ PEREIRA LEAL Bioinformatics - Curing diseases and saving the economy without leaving your computer Switch, Coimbra, Portugal May 2010
Toward a Translational Science of Mental Illness: A Perspective on 5-HT from Systems Neuroscience 1st São Paulo School of Translational Science AC Camargo Hospital São Paulo, Brazil April 2010
From Evolutionary cell biology to translational research IMM Lisbon, Portugal July 2010 Translating bioinformatics research for health, biotech and the economy Encontro com a Ciência e Tecnologia em Portugal, Ciência 2010 Lisbon, Portugal July 2010
Translational Science of Mental Illness Two Perspectives from Systems Neuroscience 1st São Paulo School of Translational Science AC Camargo Hospital São Paulo, Brazil April 2010
From bioinformatics to translational bioinformatics Interbio Barcelopa, Spain October 2010
Neural mechanisms underlying odor-guided decisions Form and Function of the Olfactory System Workhop Janelia Farm Ashburn, USA May 2010
PEDRO LIMA Glutamate Receptors in Pollen Tubes IASPR, University of Bristol (Selected Abstract) Bristol, UK August 2010
Neural mechanisms for decision making in the rat: variability and uncertainty in brain and behavior Oxford University Oxford, UK June 2010
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IGC ANNUAL REPORT ‘10
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Reading out neural circuits for decision-making in the rat Rochester CVS Symposium: Photons and Neurons University of Rochester NY, USA June 2010
ANA MENA Raising awareness on Animal Research 11th PCST New Delhi, India December 2010
Odor-guided decisions: Behavior and sensory representations Computational and Cognitive Neuroscience Course CSH Asia Suzhou, China July 2010
CHRISTEN MIRTH Uncovering how larvae regulate foraging strategies and how these strategies evolve in the genus Drosophila Janelia Farm Larval Olympiad Meeting Ashburn, USA June 2010
Neural mechanisms for rapid perceptual decisions EMBO|EMBL Symposium: Structure and Function of Neural Circuits Heidelberg, Germany September 2010
Ecdysone regulates a switch in larval burrowing behaviour at critical weight in Drosophila 18th International Ecdysone Workshop Ceske Budejovice, Czech Republic July 2010
Neural mechanisms for olfactory decision-making Instituto de Neurociencias Alicante, Spain Dec 2010
The development and evolution of foraging behaviour and social interaction in larvae of the genus Drosophila Bangalore Maggot Meeting: Neural Circuits to Behaviour Bangalore, India July 2010
Neural mechanisms for decision making in the rat Uncertainty in brain and behavior Adrian Seminar University of Cambridge Cambridge, UK December 2010
MIGLA MISKINYTE Role of biotic interactions in microbial adaptation ECCMID 20th Vienna, Austria April 2010
MOISES MALLO HOXing through the vertebrate axial skeleton Dept of Zoology and Animal Biology, Sciences III University of Geneva Switzerland April 2010
ELODIE MOHR CD8 T cells induce T-bet in B cells that switch to IgG2a and express CXCR3 during a Th2-response 14th International congress of Immunology Kobe, Japan August 2010
The instruction manual for building the vertebral column in HOX language Instituto de Medicina Molecular University of Lisbon Lisbon, Portugal April 2010
JOANA MONTEIRO Dynamic extracellular ion fluxes during fin regeneration in Zebrafish Molecular and Cellular basis of regeneration and Tissue repair, EMBO Conference Sesimbra, Portugal September 2010
Transgenic mouse models for spine bifida and caudal regression syndrome Encontro com a Ciência e Tecnologia em Portugal, Ciência 2010 Lisbon, Portugal July 2010 Old Hox genes playing new tricks to build the mouse skeleton EMBO Practical Course Split, Croatia September 2010
LUCIANA MORAES Parasite sequestration in a murine model of placental malaria Instituto de Higiene e Medicina Tropical Lisbon, Portugal June 2010
Animal models for the study of development Workshop Animal Models for Human Disease Madrid, Spain October 2010
MASAYOSHI MURAKAMI Neural substrates of impulsive decision making and its withholding Workshop on the Computational Properties of the Prefrontal Cortex Whistler, BC, Canada September 2010
Building the vertebrate skeleton with Hox genes COST/ISF Workshop on the Function of Hox &TALE Homeoproteins in Development & Disease Haifa, Israel November 2010
BEATRIZ OLIVERA Discrete dynamical modelling dealing with molecular networks' modularity IGC Post-doc Meeting Oeiras, Portugal October 2010
The making of the vertebrate axial skeleton by Hox genes Joint Meeting of the Portuguese and Spanish Developmental Biology Societies Badajoz, Spain November 2010
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IGC ANNUAL REPORT ‘10
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MICHAEL PARKHOUSE Host vs Pathogen: the game is drawn but the fight goes on Instituto de Higiene e Medicina Tropical Lisbon, Portugal February 2010
Nutritional value-based decisions in Drosophila Department of Bioengineering, Imperial College London London, UK August 2010 The Molecular and Neuronal Control of Nutrient Choice in Drosophila University College London London, UK August 2010
Estratégias racionales para el desarollo de una vacuna Feria Latin Americana de Desarollos Tecnicos Universidade Nacional Autonoma de Mexico Mexico March 2010
The Molecular and Neuronal Control of Nutrient Choice in Drosophila ESF-EMBO conference on Functional Neurobiology in Minibrains: From flies to robots, and back again Sant Feliu de Guixols, Spain October 2010
Host-Pathogen Interaction Host-Pathogen Interactions Braga, Portugal April 2010
The Molecular and Neuronal Control of Nutrient Choice in Drosophila 14th Portuguese Obesity Conference Porto, Portugal November 2010
Estratégias racionales para el desarollo de una vacuna Sociedade Catalana de Inmunologia Barcelona, Spain April 2010 Mecanismos de evasión del patógeno Intituto Biomédicas de la Universidad de Carabobo Maracay, Venezuela September 2010
LUÍS ROCHA Roundtable panelist Carnegie Mellon University, XI Annual Portuguese American Post-Graduate Society (PAPS) Pittsburgh, USA April 2010
Mecanismos de Evasión del Patógeno: Herramientas Prefabricadas para el Control de Enfermedades Infecciosas y No-infecciosas Instituto de Investigaciones Biomédicas Mexico November 2010
Semiotic Closure: material symbols in evolution Columbia University, The Barnard Interdisciplinary Workshop on Embodiment USA July 2010
Mecanismos de evasión del patógeno Reunión Maestros de la Parasitologia Mexico December 2010
Exploring the Evolutionary Role of RNA Editing with Computational Models Lehigh University, Department of Biological Sciences USA September 2010
Como preparar vacunas Temas selectos de la Inmunologia Avanzada Universidad Puebla Mexico December 2010
Reality is stranger than fiction: Exploring the Evolutionary Role of RNA Editing with Computational Models Theoretical Biology Seminar series of the CREA-CNRS Paris, France November 2010
JOSEPH PATON Time and learning in the rodent striatum Batsheva Symposium on Reward and Decision-making in the Brain Jerusalem, Isreal Febuary 2010
Emergent Computation in Biochemical Networks: what material representations tell us about autonomy Workshop on Emergence, Complex Systems Institute Paris, France November 2010
CARLOS PENHA-GONÇALVES Host genetic factors in murine and human malaria Instituto de Medinia Molecular Lisbon, Portugal April 2010
ANA BÁRBARA SANTOS Chloride channels in Pollen Tubes 15th International Workshop on Plant Membrane Biology (Selected abstract) Adelaide, Australia September 2010
Malaria and pregnancy in rodents: pathogenesis and parasites Nobel Conference: Pathogenesis of severe Malaria June 2010
MIGUEL SEABRA Rab GTPases in membrane traffic and disease 3rd Annual Meeting of the German Society for Cell Biology Regensburg, Germany March 2010
CARLOS RIBEIRO The Molecular and Neuronal Control of Nutrient Choice in Drosophila 1st Nutritional Homeostasis Workshop Bonn, Germany May 2010
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Rab GTPases, membrane traffic and disease Intracellular Trafficking Processes, Weizmann Institute of Science Tel-Aviv, Israel May 2010
ANA SOUSA Fisher’s model in the context of compensatory evolution to antibiotic resistance StaM2010 - Statistical Modelling: Challenges in Health Lisbon, Portugal May 2010
Terapia Génica: substituir genes que não funcionam Tedx Lisboa Lisboa, Portugal May 2010
DANESH TARAPORE Modelling collective systems: from cells to social insects to robots Department of Biochemistry. Indian Institute of Science Bangalore, India. October 2010
Rab GTPases in membrane traffic and disease DIIID Seminar Kings College London, UK May 2010
LUIS TEIXEIRA Non-Mendelian inheritance of tolerance and resistance to pathogens Tolerance to infection Arrábida, Portugal October 2010
Medicina Molecular: mecanismos de doença e novas terapias Centro de Malária e Donças Tropicais (CMDT) Instituto de Higiene e Medicina Tropical Lisbon, Portugal June 2010
Host-microorganism interactions Gameets 2010 Curia, Portugal December 2010
Mechanisms of Rab GTPase-dependent disease Gordon Research Conferences: Lysosomes & Endocytosis Andover, NH, USA June 2010 Mechanisms of melanosome transfer in human skin 16th Meeting of the European Society for Pigment Cell Research Hinxton, United Kingdom September 2010
HENRIQUE TEOTÓNIO Adaptation from standing genetic variation in C. elegans DFG-evolution of host parasite interactions Kiel, Germany February 2010
Rab GTPases in regulated secretion and Disease 6th International Conference on the Tear Film and Ocular Surface Florence, Italy September 2010
Adaptation from standing genetic variation in C. elegans New York University, New York/USA May 2010
Intracellular membrane traffic and retinal degeneration: from bench to bedside The Doctor Jessie Mole Lecture University of Oxford Oxford, UK December 2010
Adaptation from standing genetic variation in C. elegans University of Maryland, College Park/USA May 2010 Recombination load in experimental C. elegans Caenorhabditis elegans Evolution Meeting, Hinxton/UK May 2010
MIGUEL SOARES SIGNALING 2010 Rio das Pedras, Brazil February 2010
ANA RAQUEL TOMÁS Oct4 role in self - renewal of Apical Ectodermal Ridge during Limb Development Joint Meeting of the Portuguese and Spanish Developmental Biology Societies Badajoz, Spain November 2010
36th Annual Meeting of the European Group for Blood and Marrow Transplantation 2010 Vienna, Austria March 2010
SANDER VAN DER NOORT Immune Selection and Within-Host Competition Can Structure the Repertoire of Variant Surface Antigens in Plasmodium falciparum Workshop on Dynamical Systems Applied to Biology and Natural Sciences Universidade de Lisboa Lisbon, Portugal February 2010
Fondation des Treilles - Break down of tolerance to self: from innate immunity to autoimmune diseases Nice, France July 2010 Cell Symposia - Inflammation and Disease Lisbon, Portugal September 2010
Climate and ILI incidence Centro de Geofísica, Instituto Dom Luis Universidade de Lisboa Lisbon, Portugal April 2010
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CONFERENCES, MEETINGS, WORKSHOPS
Influenzanet research Workshop Epiwork, Amsterdam, The Netherlands May 2010
IGCxIMM IMMUNOLOGY CLUB Organisers: Instituto de Medicina Molecular (Lisbon) and IGC post-docs
Influenzanet: internet-based monitoring of ILI 2003-2010 First Annual Symposium Lessons from the 2009 H1N1 Pandemic Influenza Center for Communicable Disease Dynamics Boston, USA June 2010
Every other month immunologists from the Instituto de Medicina Molecular and the Instituto Gulbenkian de Ciencia meet for three formal lectures given by members of the two institutes, followed by informal discussions. The workshop host about 70 participants.
The Influenzanet self-reporting system warrants consistency in epidemic monitoring across countries and seasons European Scientific Conference on Applied Infectious Disease Epidemiology (ESCAIDE) Lisbon, Portugal November 2010
COMMUNICATING SCIENTIFIC RESEARCH 2010 18 - 20 January 2010 Organisers: Ana Godinho, Silvia Castro and Monica Dias (IGC); Sofia Araujo (Molecular Biology Institute of Barcelona); Voice of Young Science Network (UK) Funded by: COST - European Cooperation in Science and Technology; British Council Portugal
NÉLIA VARELA Characterizing the CO2 neuronal circuit: the initial steps DrosTuga Lisbon, Portugal December 2010
The aim of this workshop was to provide scientists with tools to effectively communicate scientific research to the general public and the media. Topics included: science and the media, writing for the media, being interviewed, science communication on the web, planning and developing public engagement in science projects. Sessions were led by science communication professionals and journalists. A total of 24 participants took the workshop, from 12 different Portuguese research and science centres, and six foreign research centres. AMeeGus 21 - 23 January 2010 Organisers: PhD Student delegates AMeeGus is the annual retreat of IGC PhD students, where students present their research to the IGC community and invited speakers. THE BIOINFORMATICS ROADSHOW 9 - 11 February 2010 Organisers: Pedro Fernandes (IGC) Funded by: European Commission FP7 Capacities Project SLING At this course participants learnt: about the different sequence searching tools available at the EBI and which ones are appropriate for different applications; to understand, search and retrieve information from proteins databases: sequence, family, motifs, domains and structure; about PDBe services, function from structure and other resources and tools for protein structure data; to search public databases such as ChEMBL and PubChem, for small molecules of biological interest and use related bioinformatics databases and services that cross-reference small molecule data; small RNA's overview and related bioinformatics resources. IMAGIS: PRACTICAL COURSE ON IMAGE ACQUISITION IN IMMUNOLOGY 12 - 18 June 2010 Organisers: Carlos Tadokoro and Jorge Carneiro (IGC); Iris Caramalho (Instituto de Medicina Molecular, Portugal) Funded by: Calouste Gulbenkain Foundation; Portuguese Society of Immunology; EFIS; Bitplane ImagIS was a hands-on course on imaging acquisition in the immune system. During the week, the 12 participants were given the opportunity to perform a full image acquisition experiment, using state of the art imaging techniques, under guidance of an internationally renowned faculty.
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PUBLIC ENGAGEMENT IN SCIENCE
EMBO COURSE - DEVELOPMENTAL IMAGING 1 - 9 October 2010 Organsiers: Gabriel Martins (Universidade de Lisboa, Portugal); Nuno Moreno and José Feijó (IGC) Funded by: EMBO - European Molecular Biology Organisation The aim of this course was to expose, train and discuss cutting-edge of live cell microscopy in the field of animal and plant development biology. The course was developed for advanced students and user-facility managers. IGC POST-DOC MEETING 12-14 October 2010 Organisers: IGC Post-doc Committee The annual meeting of IGC post-docs, made up of 30min sessions for presentations and informal discussion, amongst post-docs and other researchers at the IGC. GAMeets 27- 28 December 2010 Organisers: Mónica Bettencourt Dias and Greta Martins (IGC); Sofia Araújo (Molecular Biology Institute of Barcelona) The 2010 annual Gulbenkian Alumni meeting (GAMeets) was dedicated to the 15th anniversary of the Gulbenkian PhD programmes. The meeting was attended by around 100 alumni, from across the globe, and several leading scientists: Jonathan Howard (member of the IGC Scientific Advisory Board and Professor at the University of Cologne, Germany), Maria Leptin (Director of EMBO - European Molecular Biology Organisation), Diogo Lucena (Trustee for Science at the Fundação Calouste Gulbenkian), Leonor Parreira (Director of the PGFMA programme), Zach Mainen (Director of the INDP programme) and António Coutinho (Director of the IGC and founder and pioneer of the initial PhD programmes). To maximise the number of speakers from each programme, an intensive schedule featured 5-minute talks by alumni of the in-house PIBS (Programme in Integrative Biomedical Sciences), the 7 PGDBM (Programa Gulbenkian de Doutoramento em Biologia e Medicina) and 5 PGDB (Programa Gulbenkian de Doutoramento em BioMedicina) programmes, in addition to current Gulbenkian programmes that have not yet produced alumni, such as the PGFMA (Programa Gulbenkian de Formação Médica Avançada) and INDP (International Neurosciences Programme).
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SCIENCE COMMUNICATION AND OUTREACH Head: Ana Godinho
Impactof press on media agenda dippings/PR ratio 2008-2010
PhD in Developmental Neurobiology University of London, UK
25.0 20.4
20.0
7
15.0
13.2 9.5
10.0 5.0
The IGC runs a dedicated science communication and outreach programme which actively engages IGC researchers and staff in its two main aims: to raise the profile of the IGC and its research, both nationally and internationally, and to promote public engagement in science. A further, closely linked goal, is to provide scientists with tools to effectively communicate scientific research to non-specialist audiences, specifically to engage the general public and the media. Projects are based on two-way, dialogue-based interactions between IGC researchers, students and staff with a range of audiences: the media, students, teachers, the general public, artists and policy makers. MEDIA RELATIONS The science communication team has established a sustainable strategy for communicating with the media through the establishment of strong links with Portuguese and international media. Our database of national and international print, broadcast and online media includes the two major science news agencies - Eurekalert in the USA and Alphagalileo in Europe - thus reaching a population of over 7,000 reporters, in over 60 countries. Overall, 411 news clippings mentioning the IGC were monitored in 2010: 263 in Portuguese media (64%) and 148 in the international media (36%).
GROUP MEMBERS Sílvia Castro (Post-doc, Media Projects Officer) Filipa Barbosa (Post-doc, Schools Outreach) Ana Mena (Post-doc, Animals in Research Project Officer) Vitor Faustino (Gripenet Manager) Catarina Júlio (Trainee)
PT
300
1
PLAY-DOUGH CELLS AND SECRETS OF TASTE HANDS-ON ACTIVITIES FOR SCHOOL SCIENCE WEEK Sylvia Phillips Primary School, Carnaxide Target audiences: Years 3 and 4 (3º, 4º anos)
3
4
PLAY-DOUGH CELLS AND CHICK EMBRYOLOGY HANDS-ON ACTIVITIES EBI Santa Maria Primary School, Beja Target audiences: Year 4 (4º ano) and Year 9 (9º ano)
250 200
94
0 2008
2009
2010
3
2
5
Q&A SESSION AT EXPO AMADORA CAREERS FAIR Fórum Luís de Camões, City of Amadora Target audiences: Year 7 - 12 (7º - 12º anos)
6
DNA EXTRACTION FROM STRAWBERRIES HANDS-ON ACTIVITY EB2/3 Olivais School, Lisbon (2nd visit) Target audiences: Year 5 (5º ano) to Year 9 (9º ano) Participants: Sílvia Castro and Catarina Júlio (Science Communication and Outreach)
7
BIODIVERSITY AND SCIENCE CAREERS PRESENTATIONS Alexandre Herculano Secondary School, Porto Target audiences: Year 11 (11º ano), Year 12 (12º ano)
0 2008
2009
2010
Print, broadcast and online media coverage 2008-10 PRESS
300
BROADCAST
276
ONLINE 271
250 200 150
118
100
SCIENCE PROJECTS SUPPORT PROGRAMME Through this programme the Science Communication and Outreach team works with IGC researchers to provide supervision, theoretical and experimental support to secondary school students carrying our science projects.
101
82 60
39 15
11
2008
2009
0 2010
In 2010, just under 20 IGC researchers supported 10 projects, from 10 different schools.
PAPERS
SCIENCE COMMUNICATION
CALL
TALK AT A CONFERENCE
11
10 8
8
77
4
6
6
6 3
3 2
2
11
1 00
0
0 2008
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5
5 6 1
41
AWARDS/PRIZES
PUBLIC ENGAGEMENT IN SCIENCE
10
153
150
12
MEET THE GENE MACHINE PLAY AND DEBATE (ON ISSUES AROUND GENETIC TESTING) Bernardino Machado Secondary School, Figueira da Foz Target audiences: Year 11 (11º ano) and Year 12 (12º ano)
18
15
148
Number of press releases (by topic) 2008-10
PLAY DOUGH CELLS HANDS-ON ACTIVITIES Colégio Centeio Private School, Setúbal Target audiences: Year 1 (1º ano) and Year 2 (2º ano)
19
INT.
263
50
2
2010
Spontaneous media enquiries received 2008-2010
20
275
50
OUTREACH TO SCHOOLS The Science Communication and Outreach team and IGC researchers visited 7 schools, where they carried out several outreach activities, including handson experiments, presentations, discussions and debates. Approximately 12 researchers took part in these activities, throughout the year.
4
2009
Media Coverage 2008-10 Number of clippings in Portuguese and international media
100
SCHOOLS
2008
COLLABORATIONS UPIN - Universidade do Porto, Portugal Instituto de Investigação Científica Tropical (IICT), Portugal Centro Regional para a Inovação do Algarve (CRIA), Portugal Fundação do Museu da Ciência - Universidade de Coimbra, Portugal Instituto de Biologia Molecular e Celular (IBMC), Portugal Centro de Astrofísica da Universidade do Porto (CAUP), Portugal Natura Algarve, Portugal Voice of Young Science, UK Calouste Gulbenkian Foundation - UK Branch, UK Centre for Modern Art (CAM), Calouste Gulbenkian Foundation, Portugal ESTOOLS, University of Sheffield, UK French Embassy in Portugal, Portugal XENOME, University of Padua, Italy
Research developments by IGC scientists are announced through press releases, which are covered in national and international media. In 2010, a total of 16 press releases were sent out, generating a total of 326 news items. On average, each press release generated 20.4 news items. The IGC has established itself as a major point of call for journalists. In 2010, a total of 18 spontaneous media enquiries were received (i.e. enquiries and requests not directly related to press releases sent out by or media contacts made by the IGC).
0.0
150
2009
2010
Topics of projects carried out by students: • Alternative cancer therapies • Science Fairs • Genetics • Genetics and forensic science • Science and ethics • Genetically modified organisms • Genetic engineering • Embryology and Developmental biology
The schools outreach programme includes hands-on experiments with the students and informal scientific and career discussions with IGC researchers.
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Support provided: • Discussions with researchers • Laboratory protocols: • DNA electrophoresis; E. coli conjugation; Drosophila maintenance • and crossings • Practical laboratory work: DNA electrophoresis; Drosophila crossings; microbiology • Visit to IGC facilities and laboratories: Drosophila facility; • microbiology labs; rodent facility • Background literature • Talks by researchers at the school
was of the Open Day was to provide the public a glimpse of the varied, international, collaborative research environment at the IGC, and engage visitors of all ages in research practices and issues. All activities were planned, developed and implemented by IGC researchers, coordinated by the science communication team. Over 100 IGC researchers and staff facilitated a range of hands-on activities, guided tours of laboratories, the Top Models room, showcasing the model organisms studied at the IGC, and a 'Dress up like a Scientist' activity. Furthermore, two plays were especially developed for the open day: Who's afraid of Neurosciences?, and Ladies and Gentleman: Meet the Gene Machine, the latter followed by a debate on genetic testing. Questionnaire-based assessment of visitors' views showed that 82% of visitors came with family members; 65% claimed to have visited the IGC out of interest for science topics; 96% of respondents considered the visit to have been very good or good; the favourite activities were the visits to the laboratories and the 'Top Models' room.
LABORATORY PLACEMENTS IGC research groups and facilities welcome secondary school and undergraduate students for summer and/or holiday projects, with the aim of giving students the opportunity to participate in research projects.
SCIENCE AND ART
Some of the students hosted in 2010 included:
MORPHOGENESIS The Calouste Gulbenkian Foundation initiated a cross-cultural inter-disciplinary project inspired by International Year of Biodiversity 2010, with a view to forming a trans-national network, involving science research, arts and crafts.
BRAGANÇA DISTRICT STUDENTS (NORTHEAST PORTUGAL) 29 March - 9 April Seven final year students (12º ano) from schools in the northeastern towns of Vila Flor, Mogadouro, Bragança and Moncorvo, selected as the best in their class by their teachers, spent their Easter holidays in one of the following laboratories: Neurobiology of Action Group, Patterning and Morphogenesis Group, Flow Assisted Cell Sorting Facility.
The British artist Rob Kesseler, who has extensive experience working with botanical scientists at Kew Gardens (UK), worked with the scientists at the IGC exploring a variety of microscopic processes, examining micro patterning within samples he collected from Portuguese wildflowers, and also animal models (fruit fly, butterflies, ants and mice) used within the IGC. Besides a collection of large-scale prints, Rob Kesseler developed a project with the Portuguese porcelain manufacturer, Vista Alegre, based on the images constructed during his residency at the IGC.
WINNERS OF RESISTENTES! COMPETITION FOR DARWIN 2009 30 August - 12 September To mark Charles Darwin's 200th anniversary in 2009, the IGC developed and distributed an E.coli conjugation kit for high schools - the Resistentes! Kit - based on the X-Bacteria activities developed by the Wellcome Trust (UK). The best reports sent back by students were selected and six of the winners carried out two week-Summer projects in the following IGC laboratories: Epigenetc Mechanisms, Evolution and Development, Flow Assisted Cell Sorting Facility.
C2 Programme The IGC and the Centre for Modern Art (CAM) of the Gulbenkian Foundation set up a year-long programme of exchanges between artists and scientists. In each trimester of the 2010-11 season, three stages occur: an artist showing at CAM presents his/her work at the IGC; CAM holds a guided tour of the show for IGC researchers, staff and friends; an IGC scientist gives a scientist-view on the artist's work, at a public tour of the exhibition at CAM.
RESEARCHERS’ NIGHT 2010: SETTING THE STAGE II 24 September 2010 Venues: Oporto, Coimbra, Lisbon, Olhão Funding: European Commission Framework Programme 7, People programme (FP7-People)
Session in 2010: EXHIBITION 'TEACHERS', AT CAM Talk at IGC by Rui Sanches Tour of the show by Thiago Carvalho (Head of Graduate Studies at IGC).
For the third year in a row, the IGC was a partner in European Researchers’ Night, an annual initiative of the European Commission, aimed at bringing scientists and the public together, simultaneously across several European countries. Setting the Stage II built on the previous year's project (coordinated by the IGC) to engage scientists and the public through theatre, interactive activities, and sports. The IGC coordinated the Impact Assessment work package of the project; several IGC researchers took part in the theatre productions; the science communication team developed and facilitated an especially designed hands-on activity for the project. Across the four cities involved, the activities reached a total of 18,500 visitors.
GRIPENET Gripenet is a syndromic surveillance system that monitors the activity of influenza-like-illness (ILI), in near-real time, with the help of volunteers, via the Internet. This surveillance system is based on the voluntary online participation of the public who, on a weekly basis, respond to an internet-based questionnaire about flu symptoms. The system includes a broad range of science communication and education activities and functions as an interactive project. Since 2009, it is a part of the FP7-funded project, EPIWORK.
2010 IGC OPEN DAY - THE SCIENCE REPUBLIC 9 October 2010 Funding: Oeiras City Council (Oeiras Vive a Ciência Project) Supported by: Roche, Fisher Scientific, Biorad, Quilaban, Dagma, Normax, VWR, Leica Microsistemas s.i.u, Sarstedt, Enzifarma, STAB Vida, FC&F Publicidade em Comboios. The 5th IGC open day, The Science Republic, brought approximately 1,200 visitors to the IGC. Scheduled so at to coincide with the week of the celebrations of the 100th anniversary of the Portuguese republic, the aim
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The Science Republic for the 5th IGC open day brought close to 1,200 visitors, of all ages, to the institute.
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In 2010, "Gripe, câmara, acção!" (Flu, camera, action!), a video competition for schools was organised. Students were invited to submit one minute videos on the topic of Influenza. Videos were short listed by a panel and then submitted for online voting. The winning videos were shown on national television (a partner in the project). Also in 2010, the contents of the Gripenet website was updated, as was the e-newsletter; social networks (Facebook and Twitter) accounts were set up widen the community of participants and help promote engagement in specific subjects related to influenza. The first internet-based monitoring service for dengue was set up, as a collaboration between the IGC and the Universidade Federal da Bahia, Brazil.
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Morphogenesis and Jardim Porcelânico - two exhibitions by British artist Rob Kesseler, created during his residency at the IGC.
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FUNDRAISING INSTITUTIONAL COMMUNICATION - PUBLICATIONS
Head: Maria João Leão
In-house publications produced in 2010 • IGC 2009 Annual Report • Quinta Grande, the IGC newsletter
PhD in Cancer and Virology University of London, UK
Articles and features in external publications In 2010, the Science Communication and Outreach team worked with several research and R&D publications on articles featuring the IGC and/or IGC research:
The IGC develops an in-house programme of public fundraising activities aimed at involving the scientific community, the private sector and the general public in research funding.
• "Evolution: antibiotic resistance and putting back the evolutionary clock", in Concelho de Laboratórios Associados (eds) 100 Research Themes in Portugal. Lisbon: Ministério da Ciência, Tecnologia e Ensino Superior; • "Malaria: genetics, inflammation and modelling", in Concelho de Laboratórios Associados (eds) 100 Research Themes in Portugal. Lisbon: Ministério da Ciência, Tecnologia e Ensino Superior; • "A new life for research in Portugal", The Scientist, 1 March 2010.
THE IGC - EVERYTHING IS NEW PARTNERSHIP This partnership, established in 2007 between IGC and Everything is New, the organiser of the OptimusAlive!Oeiras music festival, aims to bring science closer to the Portuguese society and to raise funds for scientific research. This unique partnership is a good example of how the private sector and society in general may contribute to the progress of research and therefore to the future and well-being of all.
Institutional Communication - International Meetings & Conferences The IGC Science Communication and Outreach team collaborated in the public engagement and media relation components of several international scientific conferences:
IGC at Optimus Alive!10 Oeiras 8 - 10 July, 2010 Science, Music and Art came together for the third year during Optimus Alive! Oeiras10. During the three days of this major music and art event the main activities in the IGC corner were speed-dating with scientists, DNA extraction from strawberries, molecular cooking by Cooking Lab and the "Champimóvel", developed by the Fundação Champalimaud .
• Stem Cells In Biology and Disease, ESTOOLS International Symposium, ESTOOLS - Integrated Project in the European 7th Framework Programme (FP7), May 2010; • Os Desafios Éticos das Neurociências - Colóquio Franco-Português (French-Portuguese Colloquium on the Ethical Challenges of Neuroscience), May 2010; • Xenotransplantation nowadays, Xenome - Integrated Project in the European 6th Framework Programme (FP6), October 2010.
Around 80 IGC volunteers made these activities possible for more than 900 young people that visited the IGC space during the three days of this event. Feedback showed that 49% of visitors that returned the questionnaires were aged between 20 and 29 (average age 24) and 34% were aged between 10 and 19 (average age 17.04). Optimus Alive! Oeiras - IGC research fellowships For the second year running, Everything is New funded new research fellowships, for young graduates wishing to pursue a career in scientific careers. Already, over 200 young graduates around the country have applied to these fellowships, in both editions.
Institutional Communication - Social Networks and New media In 2010 we continued to use new media and social networking to communicate effectively with broad audiences, by providing regular updates on research developments and outreach, in both English and Portuguese:
The 2010 fellowships were awarded to Sam Viana (26) and Francisco Freixo (23), by an international jury to develop one-year research projects in Biodiversity (in the Population and Conservation Genetics Group) and Malaria (in the Disease Genetics Group). These projects were carried out at the IGC, in Madagascar and on the island of Príncipe.
• Facebook (6,445 fans, December 2010) • Twitter (800 followers, December 2010) • YouTube (20 movies; 4380 views, December 2010)
New media In addition to the high impact of this partnership in the Media, a Facebook page was created to raise awareness of and describe the IGC initiatives carried out at the festival, as well as the research life of the fellowship holders, at the IGC and in Madagascar and Principe. Two videos, available at the IGC address on YouTube, give an insight into the IGC presence at both OptimusAlive!Oeiras, in 2008 and 2010.
Festival goers visiting the IGC space at OptimusAlive!Oeiras 2010, and two of the Optimus fellows with the director of the company Everything is New.
SCIENCE AT “MUNDO MIX” 14 - 16 May, 2010 The IGC, together with Associação viver a Ciência (VAC) was present at “Mundo Mix”, a three-day event of culture, fashion, music, art and multimedia at Castelo de São Jorge, in Lisbon. Our goal was to take science, the IGC and VAC to unexpected venues reaching non self-selected publics. Visitors had the opportunity to participate in different science related activities and also to see and taste ice creams made with liquid nitrogen, agar spaghetti and a molecular cocktail, prepared by Cooking Lab, a company set up by scientists. Through the purchasing of the IGC mugs and postcards from the VAC exhibition Laboratório de Imagens, the public contributed to scientific research in Portugal.
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'Four good reasons to drink in science' - the new Science collection for fundraising, in partnerships with the porcelain manufactureres Vista Alegre.
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FUNDRAISING ACTIVITIES ORGANISED BY THE IGC PHD DELEGATES Several fundraising activities were organised in 2010 to raise funds for the 4th PhD AMeeGuS meeting, via donations from attendees at the events, both from IGC staff and the general public. These events included: • Wine Hour (21 October 2010) • IGC Post-Doc Meeting party (15 October 2010) • S. Martinho Party (12 November 2010) • Table football Tournament (25 November 2010) • Raising funds by selling IGC mugs between friends and family (December 2010) IGC MERCHANDISING PRODUCTS A series of IGC products were displayed at IGC and at Gulbenkian Foundation with the aim of raising public awareness of IGC research and additional funds for science. • IGC calendar for 2010 - The theme of the calendar was Scientific Awards, and aimed to promote biomedical research and the scientists of IGC • IGC Mugs and Pins PARTNERSHIP BETWEEN IGC AND VISTA ALEGRE A new partnership was establisehed in 2010 between IGC and Vista Alegre, a prestigious and market leader Portuguese porcelain manufacturer. The new porcelain Science Collection was the result of this partnership. Original scientific images, captured by young IGC scientists were re-designed to be printed on coffee cups and mugs. These products were made available in December 2010, at the IGC and at Gulbenkian Foundation, and during 2011 will be available at the Vista Alegre shops around the country. PARTNERS AND SPONSORS Several partnerships and sponsorships have been established to support scientific research, education and science communication and outreach activities at IGC, either financially or in kind: Alfagene Bio-Rad Biognóstica Bioportugal Câmara Municipal de Anadia Câmara Municipal de Oeiras Ciclone Dagma, Lda Designways DIAS DE SOUSA ENFIN Enzifarma Everything is New FC&F-Publicidade em Comboios Fisher Scientific IBET
ILC IMM Champalimaud Foundation ITQB Izasa Leica Leica, Normax NYZtech OptimusAlive!Oeiras10 Portugal Telecom (PT) Quilaban Stab Vida Starstedt Vista Alegre VWR Werfen Group
The IGC is under Scientific Sponsorship Law. This law provides tax benefits for science-related donations by either individuals or companies.
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We are grateful to everyone at the IGC, researchers, students and staff, who supplied information, text and images used in this report. PROJECT MANAGER ANA GODINHO PROJECT OFFICER ELIANA CARVALHO LAYOUT AND DESIGN DESIGNWAYS - WWW.DESIGNWAYS.PT The Instituto Gulbenkian de Ciência Annual (IGC) Report is also available to download from the IGC website at www.igc.gulbenkian.pt. If you would like to receive a copy of this report, please contact: Science Communication and Outreach Instituto Gulbenkian de Ciência Rua da Quinta Grande, 6 2781-156 Oeiras Portugal Tel: +351 440 7959 Fax: +351 440 7970 E-mail: info@igc.gulbenkian.pt This is an open access publication, and with the exception of images and illustrations, the content may, unless otherwise stated, be reproduced free of charge in any format or medium, subject to the following conditions: content must not be used in a misleading context, the IGC must be credited as the original author and the title of the document specified in the attribution. The IGC was founded by the Calouste Gulbenkian Foundation, a Portuguese private institution of public utility whose statutory aims are in the fields of arts, charity, education and science. Created by a clause in Calouste Sarkis Gulbenkian's will, the Foundation's statutes were approved in 1956. The headoffice is located in Lisbon.
First published by the Instituto Gulbenkian de Ciência, 2011 © Copyright Fundação Calouste Gulbenkian 2011