Conway Focus Issue 11 Sept 2010

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collaborator scoops Irish chemotherapy Times Innovation Award PredictingConway patient responses to ovarian cancer

Centre of Excellence hosts international workshop these cells also display a compromised work, Dr McCann said “Up to 30% of

Irish biopharmaceutical development Late diagnosis, recurrence and company, Sigmoid Pharma recently scooped chemoresistance all contribute to the overall Innovation of the Year award at the high morbidity and mortality in the inaugural Irish Times All-Island As a European Centre of Excellence, the ovarian cancer patients. Currently, Innovation Awards. The life-science SME, Department of Rheumatology St Vincent’s there is by noUCD way to identify in those founded pharmacology graduate, Dr Ivan Coulter, has actively collaborated with women who will benefit most from University Hospital was chosen to host an Conway Professor the firstFellow, linetwo-day therapy ofCormac choice, a international workshop onTaylor March since being granted a Science Foundation paclitaxel-based chemotherapy. 26th & 27th 2010. Sponsored by Roche Ireland industry research partnership award

Pharma, in 2004. the Participate workshop gave

May

Research led byaward Conway Fellow, Dr.stellar twenty from centres in The Irishrheumatologists Times recognises the innovative performance ofand Sigmoid Pharma Amanda McCann PhD collaborators Europe and Australia the opportunity to in their of research in St.application James’, Holles Streetand anddevelopment. Beaumont witness the care of patients with rheumatoid The company has developed two new Hospitals in Dublin has focused ondrug arthritis (RA) at St Vincent’s. technologies, LEDDS™ and SmPill™, which not the deficiency protein 2 13:12 2010.qxd:Layout 1thecopy 07/05/2010 onlymitotic enhancearrest solubility and permeability of (MAD2). Their published the drug but can recent deliver itfindings to targeted locations the gastrointestinal tract, including the in Cell Cycle gives further insight into colon.this protein is regulated and how brings scientists closer to collaboration identifying is The Sigmoid Pharma-Taylor facilitating the role development a new its potential in a cell’sofresponse to therapeutic approach for the treatment of paclitaxel.

results in both academic outputs and the application of paclitaxel research toward clinical product response to treatment. development with indigenous companies.”

This study investigated how MAD2 is

The Participate programme focused on Dr Commenting the Taylor collaboration, regulated inon ovarian cancer focusing on Coulter said, “The collaboration with advanced treatment regimens for RAthe in Taylor the the methylation status of the MAD2 laboratory clearly practical demonstrates theofpotential clinic, including biologic promoter and thethrough effectaspects on MAD2 that can be realised focused infusion therapy carried out in the accredited levels of tumour common application of basichypoxia; research. aThe development suite that economy provides optimal care on forlike-minded RA tumour of a smartmicroenvironment will dependreflecting patients. In addition to lectures from Conway collaborative partners identifying opportunities deprived oxygen levels that is integral to Fellows, Professors Oliver FitzGerald and and realising basic and applied research chemoresistance. synergies. This collaboration, initiated through Douglas Veale, delegates heard from clinical anurse SFI research supplement, highlights the specialists about patient education, Commenting on the work, postdoctoral potential that innovative indigenous companies screening and monitoring of biological researcher Maria Prencipe PhD said, working withDr academia can realise.” therapies.

“We found methylation of Page 3 that aberrant Taylor’s collaboration with Sigmoid Pharma has the promoter region was certainly been successful by not theseinvolved metrics with in regulating MAD2 expression. Using three co-authored publications to date in two of the highest ranking in the CAIX, a marker ofscientific hypoxia,journals we found less field, Gastroenterology and Proceeding of the MAD2 protein expressed under hypoxic National Academy of Sciences, as well as the conditions. We also demonstrated that generation of proprietary innovative products down-regulation of MAD2 isjobs. associated and the creation of high-skilled with up-regulation of p21 in hypoxia, More than 15,000 people in Ireland and suggesting a role for p21 into regulating variety of in order millions of solutions people worldwide areunderstand living with the the MAD2 expression”. structural basistoday. for the difference in biological symptoms IBD Current therapeutic

tract is lined with cells that block the contents ofpatients the gut from into theto intestine. In an mayleaking not respond the current IBD patient, this barrier is broken and the standard chemotherapy (paclitaxel contents of the gut leak out into surrounding Addressing combination). the international In guests, Ms Mary /platinum order to used areas. The research team in UCD Conway Duff, of Nursing and it Ms. Kayclass of outcome, crucial aimprove modelDirector of patient IBD and, by applying aisnew Connolly, Assistant Director of Nursing for the drugs known as hydroxylase inhibitors, were that we establish what factors influence able to & almost reverse the Bone Joint completely Unit expressed hope that an individual’s response to their chemotherapy symptoms of theof disease. the experience the multidisciplinary team

and which factors explain why some

from St wouldnew provide a to template “When weVincent’s applied these drugs our IBDfor patients fail to benefit from standard model, the gut was tricked into thinking it delegates to reproduce similar care andthat first-line chemotherapy while others get was being deprived of oxygen. This activated facilities forremission”. the management of RA patients in long-term protective pathways, which in turn prevented their respective countries. the death of the cells that line the This work wastract,” supported by Professor IRCSET, Irish gastrointestinal explained Taylor. “Our pre-clinical trialEccles data can now Cancer Society and the Breast inform theResearch next phase Sigmoid Pharma product Health Fund as well as internal development pipeline”.

UCD funding.

In addition to the product that is currently in phase II clinical studies, Sigmoid Pharma is Reference: a LEDDS™-enabled formulation of developing MAD2 down-regulation in hypoxia is independent of the hydroxylase inhibitor promoter hypermethylation. Maria Prencipe, Aloysius dimethyloxaloylglycine (DMOG) to bring about McGoldrick, Antoinette S Perry, Anthony O’Grady, effective, safe and targeted delivery of this Sine Phelan, Barbara McGrogan, Patricia Fitzpatrick, potential therapeutic agent. Jenny A Watson, Fiona Furlong, Donal J Brennan, Mark Lawler, Elaine Kay and Amanda McCann. Cell Cycle Volume 9, Issue 14 Pages 2928 - 2937 July 15, 2010

Frog peptide structure selected for journal cover

inflammatory bowel disease (IBD) by bringing

together thehave research methodology ofthat the The team An image of with the previously frog peptideshown structure central Taylor group the proprietary lowered levels of MAD2 induce cellular to the work of adrug UCD Conway research team liquid/emulsion delivery system, senescence, where cells are viable but was selected as the by front cover image for the LEDDS®, developed Sigmoid Pharma. not dividing. Aprilactively 2010 edition of theImportantly, scientific journal, Commenting on the award, Professor Taylor Biochimica Biophysica (BBA);and his said, “We areetdelighted for Acta Dr Coulter Proteins Proteomics. team and & indeed it reflects well on our partnership. A key driver of successful Peptides research in the skin many species of frog scientific in of 2010 is meaningful have anti-bacterial and anti-fungal properties interaction of academia with industry that

options activity.for this chronic debilitating disease are very limited the withfuture surgerydirection often being Regarding of the thisonly viable option. The Sigmoid product, currently This particular XT-7 peptide, isolated from the inskin a phase II clinical study, uniquely enables for of Silurana tropicalis, shows potential oral delivery of a powerful drug without drug development as it has impressive activity causing systemic side-effects.

Conway collaborator scoops Irish Times Innovation Award UCD clinician scientist wins prestigious award

against the growth of bacteria and Candida Under normal conditions, the gastrointestinal albicans. However, this potential as an antias well as the ability to lyse or rupture Postdoctoral research fellow, Dr Donal Womens andacademic Infants University Hospital, results in both outputs the Irish biopharmaceutical development infective agent is restricted by itsand haemolytic May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3 mammalian cells. This innate immunity application of research toward product company, Sigmoid Pharma scooped Brennan became the first recently Irish recipient works research groupclinical of Professor activity.in the protects it from attack. These properties of development with indigenous thethe overall Innovation of the Year award at of European Young Researcher Award William Gallagher. He hascompanies.” been using the Irishare Times All-Island froginaugural skin peptides exciting from the A change the amino acid structure of Dr the at the 2010 Euroscience Open Forum the latesttoinon high-throughput protein Commenting the Taylor collaboration, Innovation The life-science SME, prospect ofAwards. being developed into XT-7 peptide can create an analogue that Coulter said, “The collaboration with the Taylor in Turin,by Italy. The award recognises screening technology to identify and founded UCDvaluable pharmacology graduate, Dr therapeutically anti-infective and antilaboratory clearly demonstrates the retains anti-infective properties butpotential without the outstanding scientists the early with validate new biomarkers of breast Ivan Coulter, has activelyincollaborated cancer agents. that can be realised through focused complicating haemolytic activity. The single Conway Fellow, Professor Cormac Taylor stages of their career who have already and ovarian cancer as well as trying to application of basic research. The development Meta-analysis by UCD researchers led by studies in humans have shown that non since being granted a Science Foundation amino acidhow substitution (glycine replaced byin demonstrated excellence atHewage national improve is interpreted Conway Fellow, Dr Chandralal andand his of a smart economy willdata depend on like-minded Conway Fellow, Professor Denis Shields has progression wasassay associated with gross Ireland industry research partnership award lysine) improves thegene. therapeutic potential of team carried out there molecular of the European levels. clinical laboratories. collaborative partners identifying opportunities determined that is nomodelling clear evidence deletions in the nef in 2004. and and applied research that defective viral sequences in a XT-7particular peptide and its analogue [G4K]XT-7 in thisrealising naturallybasic occurring peptide.

tract is lined with cells that block the contents of the gut from leaking into the intestine. In an IBD patient, this barrier is broken and the contents of the gut leak out into surrounding areas. The research team in UCD Conway used a model of IBD and, by applying a new class of drugs known as hydroxylase inhibitors, were able to almost completely reverse the of HIV nef of arethe critical in determining the rate symptoms disease. of disease progression. Professor Denis “When we applied these new drugs to our IBD Shields believes searches for modifiers of Cover of April 2010that edition of Biochimica et Biophysica model, the gut wasshould into focus thinking it progression rates now on that other Acta (BBA); Proteins &tricked Proteomics. was deprived of oxygen. This evaluation activated hostbeing and viral factors. “Systematic Dr Donal pictured at ESOF 2010prevented in Turin, Italy protective pathways, in bioinformatics turn of large Brennan quantities ofwhich data by the of as theimportant cells that in line the candeath be just refuting gastrointestinal explained Professor hypotheses thattract,” are current in the literature, as Taylor. pre-clinical trial data can now it is in“Our discovering unknown patterns”, he said. inform the next phase Sigmoid Pharma product This researchpipeline”. was funded through Science development Foundation Ireland and University College InDublin. addition to the product that is currently in phase clinical Sigmoid Pharma is tract isIIlined withstudies, cells that the contents (thomas.scharzl@ucd.ie ) block and postdoctoral developing a LEDDS™-enabled of the gut from leaking into the formulation intestine. In of an researchers, Drinhibitor David Gomez the IBD hydroxylase patient, this barrier is broken and the (david.gomez@ucd.ie) and Dr Craig Slattery dimethyloxaloylglycine (DMOG) to bring about contents Reference:of the gut leak out into surrounding effective, targeted of nef thisamino (craig.slattery@ucd.ie ) invite for Meta-analysis to and test the association ofsuggestions HIV-1 areas. Thesafe research team indelivery UCD Conway used potential therapeutic agent. acid differences and deletions with disease progression. forum schedule. a the model of IBD and, by applying a new class of

Bioinformatic analysis of HIV progression studies

The Irish Times award recognises the stellar

the Brennan, HIV-1 nef agene or certain regions Dr specialist registrar inof thein innovative performance of role Sigmoid Pharma protein play a significant in disease obstetrics & gynaecology at the Coombe their application of research and development. progression.

The company has developed two new drug HIV-infected can beSmPill™, categorised on not technologies,patients LEDDS™ and which the basis of the of years it takes for of only enhance thenumber solubility and permeability them to progress to AIDS. Some patients the drug but can deliver it to targeted locations maintain stable CD4 lymphocyte counts in the gastrointestinal tract, including theand do not go on to develop AIDS even after more colon. than 10 years of infection.development Irish biopharmaceutical A new fortnightly forum for Conway graduate The Sigmoid Pharma-Taylor collaboration isand Doctoral students Adriana Michielsen company, are Sigmoid Pharma recently scooped Scientists as to winners why longfacilitating the curious development of a these new and postdoctoral researchers will be at launched Edwina Cahill were joint the the overall Innovation ofthe thetreatment Year award term, nonprogressor (LTNP) patients do not therapeutic approach for of at in May 2010. This initiative will give early6th annual UCD Conway Postgraduate the inaugural Irish All-Island develop AIDS.bowel This Times may reflect differences in inflammatory disease (IBD) bringing th by stage researchers the opportunity to talk about Symposium held on June 18 2010. Innovation Awards. The the host, the viral genetics orlife-science environmental together research methodology of SME, the sciencegroup and issues that concern them in an founded by UCD pharmacology graduate, Dr Adriana works the colorectal research factors that could potentially be exploited for Taylor within the proprietary Ivan Coulter, has actively informal environment withcollaborated refreshments the treatment of the disease. liquid/emulsion drug delivery system, group under the supervision of Dr. with Conway Professor Cormac Taylor provided!Fellow, Content forby the forum will be LEDDS®, developed Sigmoid Pharma. Jacintha in the Education Studies inO’Sullivan model organisms have shown & that since being granted a Science Foundation Research Centre, Staward, Vincent’s University infectionindustry with nef-deficient virus shows an Commenting on the Professor Taylor Ireland research partnership award attenuated course of infection and said, “We are delighted for Dr Coulter and his Hospital. Her presentation wassome entitled in 2004. team and indeed it reflects well on the ourstellar “The effect of tumour microenvironment The Irish Times award recognises partnership. A key driverofofSigmoid successful innovative performance Pharma in scientific research 2010 isand meaningful their application of in research development. interaction of academia with industry The company has developed two new that drug

However, much of the research in the area to synergies. This collaboration, initiated through been supplement, based on observational or case adate SFI has research highlights the studies rather than rigorous, systematic potential that innovative indigenous companies scientificwith evaluation. This by doctoral working academia canwork realise.” candidate Ravindra Pushker set out to Taylor’s collaboration with Sigmoid Pharmaset has determine in a substantially larger sample certainly been successful by thesedisease metrics with if any association exists between three co-authored publications to date progression and particular amino acid in two of the highest ranking scientific journals the differences or deletions within the nefingene. field, Gastroenterology and Proceeding of the results in by both academic outputs and the On a per patient basis, there was no excess decided the members but it is envisaged components on dendritic cell function National Academy of Sciences, as well product as theof application of research toward clinical LTNP with aone or defective nef that itpatients will of include mix ofmore technology generation proprietary innovative products in colorectal cancer”. Edwina presented development with compared indigenoustocompanies.” sequences when progressors. overviews, informal and formalAutocrine research and the creation ofthe high-skilled jobs. her research on “Novel While the high ofcollaboration, amino acid Dr Commenting onfrequency the Taylor seminars, PhD viva rehearsals and and career Function of the BMP Antagonist More than 15,000 people in Ireland replacement at particular residues isGremlin: indicative Coulter said, “The collaboration with the Taylor development talks from within and beyond millions of people worldwide are living with the a Key Role in Hypoxic Pulmonary of rapid evolvement, permutation testing laboratory clearly demonstrates the potential academia. Forum committee members, PhDof symptoms IBD today. Current therapeutic showed thatrealised residues with more replacements Hypertension”. She works in the group that can be through focused student MrPaul Thomas Schwarzl options for this chronic debilitating disease are than expected were not statistically significant. application of basic research. The development Professor McLoughlin. very limitedeconomy with surgery often being the only of a smart will depend on like-minded The researchers conclude that current data viable option.partners The Sigmoid product, currently collaborative identifying opportunities provides no that individual residues in a phase II evidence clinical study, uniquely enables and realising basic and applied research oral delivery of a powerful drug without synergies. This collaboration, initiated through causing systemic side-effects. a SFI research supplement, highlights the

ofConway Conwaycollaborator postdoctoral &Symposium graduate forumInnovation Award th scoops Irish Times 6Launch annual Conway Postgraduate

technologies, LEDDS™ and SmPill™, which not only enhance the solubility and permeability of the drug but can deliver it to targeted locations in the gastrointestinal tract, including the colon.

potential that innovative companies Under normal conditions,indigenous the gastrointestinal working with academia can realise.”

Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields.

drugs as hydroxylase inhibitors, were Journalknown of Virology, Apr 2010 p3644-3653 able to almost completely reverse the symptoms of the disease.

“When we applied these new drugs to our IBD model, gut was tricked into thinking that it Adrianathe Michielsen (left) and Edwina Cahill pictured was deprived of oxygen. This activated withbeing Professor Walter Kolch, Director, UCD Conway protective Institute pathways, which in turn prevented the death of the cells that line the gastrointestinal tract,” explained Professor Taylor. “Our pre-clinical trial data can now inform the next phase Sigmoid Pharma product development pipeline”.

Taylor’s collaboration with Sigmoid Pharma has certainly been successful by these metrics with three co-authored publications to date in two of In addition to the product that is currently in the highest ranking scientific journals in the phase II clinical studies, Sigmoid Pharma is field, Gastroenterology and Proceeding of the developing a LEDDS™-enabled formulation of National Academy of Sciences, as well as the Elaine Quinn the hydroxylase inhibitor generation of proprietary innovative products Communications & Education Officer of HIV nef are critical in determining theabout rate studies in humans have shown jobs. that non dimethyloxaloylglycine (DMOG) to bring and the creation of high-skilled UCD Conway Institute of Biomolecular &Professor Biomedical Research of disease progression. Denis progression was associated with gross effective, safe and targeted delivery of this More than 15,000 people in Ireland and University College Dublin Shields believes thatagent. searches for modifiers of deletions in the nef gene. potential therapeutic millions of people worldwide are living with the progression rates should nowBelfield, focus onDublin other 4 However, much of theCurrent research in the area to symptoms IBD today. therapeutic Ireland host and viral factors. “Systematic evaluation date hasfor been ondebilitating observational or case options thisbased chronic disease are of large quantities of data by bioinformatics studies rather than rigorous, systematic very limited with surgery often being the only can be just as importantE:inelaine.quinn@ucd.ie refuting scientific evaluation. This work by doctoral viable option. The Sigmoid product, currently T: in (+353-1) 716 6706 hypotheses that are current the literature, as candidate set out enables to in a phase Ravindra II clinical Pushker study, uniquely it is in discovering unknown patterns”,716 he said. F: (+353-1) 6701 determine a substantially larger sample set oral deliveryinof a powerful drug without W:through www.ucd.ie/conway if any association exists between disease This research was funded Science causing systemic side-effects. progression and particular amino acid Foundation Ireland and University College Under normal conditions, the gastrointestinal differences or deletions within the nef gene. Dublin.

Bioinformatic analysis of HIV progression studies

The Sigmoid Pharma-Taylor collaboration is facilitating the development of a new therapeutic approach forresearchers the treatment Meta-analysis by UCD ledofby inflammatory bowel diseaseDenis (IBD) Shields by bringing Conway Fellow, Professor has together the that research of the determined theremethodology is no clear evidence Taylor group with the proprietary that particular defective viral sequences in liquid/emulsion drugordelivery the HIV-1 nef gene certainsystem, regions of the Investing in Your Future LEDDS®, developed by Sigmoid protein play a significant role inPharma. disease progression. on the award, Professor Taylor Commenting

said, “We arepatients delighted forbeDrcategorised Coulter andonhis HIV-infected can team and of indeed it reflects the basis the number of well yearsonit our takes for partnership. A keyto driver successful them to progress AIDS.ofSome patients scientific research in 2010 is meaningful maintain stable CD4 lymphocyte counts and interaction of to academia thatmore do not go on developwith AIDSindustry even after than 10 years of infection. Scientists are curious as to why these long-

On a per patient basis, there was no excess of LTNP patients with one or more defective nef

September 2010 Issue May 2010 Issue 101 11 september 2007 Issue

May 2010.qxd:Layout 1 copy

Success in EU FP7 call disease (CKD) and improve patient treatment, Conway researchers led by Dr. Tara McMorrow and Professor Michael Ryan have with particular focus on CKD arising from May 2010.qxd:Layout 1 copy 07/05/2010 13:12 3 diabetes and Page hypertension. The multisuccessfully secured €485,500 in funding as disciplinary research consortium has 25 part of an overall award to the Systems partners (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney from 15 countries and the project is due to run Disease Diagnosis and Treatment (SysKid) for five years. consortium under the European Union FP7 programme. The UCD Conway team, including postdoctoral researchers Dr. Craig Slattery and Dr. Natalia Syskid (www.SysKid.eu) was established to Martin, will utilise cell culture and animal further our understanding of chronic kidney

models to identify processes involved in early CKD progression and investigate novel strategies for preventing and slowing the progression of the disease. These studies will be integrated with clinical and epidemiological studies across the consortium using systems biology methodologies in order to develop new diagnostic strategies and treatment options to prevent CKD development. Email tara.mcmorrow@ucd.ie for details of a PhD position currently available.

GlycoExtractor advances glycan data manipulation Conway collaborator scoops Irish Times Systems model of signalling control Worm research reveals cilia disease geneInnovation functionAward

Glycomics needs the supporting framework cells, tissues and fluids. EUROCarbDB, a research infrastructure design study funded by the EU 6th Framework of extensive, well-curated databases and Commercial packages that support HPLC flexible analytical tools. Currently, this field Programme. Prospective users can access the instruments cannot facilitate the extraction of of study lacks the established, GlycoExtractor tool on large quantities of data. In an effort to alleviate http://glycobase.nibrt.ie:8080/DemoGlycoExtra comprehensive and centralised data this bottleneck within high-throughput tract lined with cells thatit block the function contents results in both academic outputs and the Irish biopharmaceutical development Fail-safe switches have been used in to turn on and off biological decisions.Dr noisyissignals, meaning can still collections, standards and information ctor/mainPage. Research by Conway Fellow, Dr Oliver the function of worm Arl13b causes the complex traits including obesity, diabetes, glycomic projects, the NIBRT team have of the gut despite from leaking into the intestine. application of research toward clinical product company, Sigmoid Pharma recently scooped mechanics andwithin electronics for years to Marc Birtwistle (SBI), one of the researchproperly major alterations to In itsan reporting protocols that exist Blacque has revealed ciliary membrane to bulge and become ReferenceIBD mental retardation andiseven cancer. adevelopment web-based tool indigenous that interfaces patient, this barrier broken and the companies.” the overall Innovation ofnew the Year awarddeveloped at what devices do information under A web-based interface for high genomics and control proteomics. ers involvedwith in this study explains that GlycoExtractor: components and inexact messages. chromatography about a gene implicated in Joubert misshapen as well as software affecting the ability throughput of contents of the gut leak outdata into surrounding the inaugural Irish Times All-Island processing of HPLC-Glycan different circumstances. They arewith the Waters the Taylor Dr Natalia V. areas. “rather than taking a ‘one piece at awithin time’ Dr Oliver these findings package to Commenting improve andon automate thecollaboration, export Researchers, Dr Natalia and Dr twodisorders Artemenko, Matthew Campbell, and Pauline The Blacque researchP.hopes team inthat UCD Conway used Innovation Awards. The life-science SME, syndrome and cerebellar other proteins to collaboration properly distribute based onArtemenko the related premise that codes Coulter said, “The with the Taylor M. Rudd Journal of Proteome Research, 2010, 9 (4), approach to understanding how these Commenting on the significance ofppclass the of will ultimately lead to a greater Matthew Campbell frombycharacterised the National Institute ofbone data to various file membrane. formats for subsequent a model of IBD and, by applying a new founded UCD pharmacology graduate, Dr (JSRDs), by blindness, the ciliary must be present for a signal to be laboratory clearly demonstrates the potential 2037–2041 The modularsignal architecture of the tool of Bioprocessing Research understanding only of JSRDs, butwere also complex transduction systems work research, Professor Kholodenko said, “We drugs known as not hydroxylase inhibitors, Ivan Coulter, & actively(NIBRT) collaborated analysis. with abnormalities, cystic kidneys, turned ‘on’.has IfTraining only one or neitheralso code that the canmanipulation be realised through led by Conway Conway Fellow, Professor Pauline Cormac Rudd Taylor facilitates of datafocused from able tohave almost completely reverse the as model Fellow, Professor They also to found that a fully functional of closely related ciliopathies such together create biological function, we now a validated mathematical developmental delay and loss of muscle application of basic research. The development is present, the signal is ‘off’. have developedsince an open other data management systems. symptoms of theand disease. beingaccess, grantedweb-based a Science Foundation Arl13b protein is needed the Meckel Gruber consider the system afor whole. Central to that represents theBardet-Biedl behaviour ofsyndrome, this of a smart economy willasdepend onnormal like-minded tone and control. The findings of this interface that facilitates extraction, querying Ireland industry research partnership award functioning of a protein transport system in as well as perhaps more common The NIBRT team are now working to integrate “When we applied these new drugs to our IBD collaborative partners identifying opportunities the systems biology approach is casting cellular signalling system”. funded through aFellow, Science and sharing of research, HPLC-glycan data generated in in 2004. New research by Conway Professor GlycoExtractor with EUROCarbDB cilia. Thisthe intraflagellar transport system phenotypes model, the gutassociated was trickedwith intocilium thinking that it and basic and applied research our realising biological understanding into a mathhigh throughput processes. Foundation Ireland President ofthe Ireland Boris Kholodenko and collaborators in The Irish Times award recognises stellar framework synergies. to provide a comprehensive highwas being deprived of mental oxygen. This activated This collaboration, initiated through (IFT) makes contact with the ciliary dysfunction such as retardation and The research was funded through a Science ematical formalism that allows us to use Young Researcher Award (PIYRA) to throughput Oliver innovative performance of Sigmoid Pharma in RIKEN, Japan has shown that evolution Glycosylation is the most common and HPLC data analysis for protective which in turn prevented amembrane. SFI research supplement, highlights the Based onplatform these results, they obesity. pathways, Foundation Ireland Centre of Science and computers and maths to understand how their application of research and development. Blacque, were recently published in the the storagepotential and annotation experimental structurally diverse post-translational the death of the cells that line the that innovative indigenous companies has provided a biological version of these proposed a newof working model for Arl13b, disease (CKD) improve patient treatment, models to identify processes involved award in earlyand Conway researchers led byhas Tara The company developed Engineering and Technology theand system ofwith CellDr. Biology. modification ofJournal proteins. More than half oftwo all new drug data. The integration of works.” next generation gastrointestinal tract,” explained Professor working with academia can realise.” He notes and “That Arl13b associates with ciliary switches similar fail-safe CKD progression investigate novel McMorrow and Professor Michael Ryan havemechanisms withnot particular focus on CKD arising from membrane where it functions at the ciliary technologies, LEDDS™ and SmPill™, which bioinformatic tools will further the gene products have been shown to be RIKEN. Taylor. “Our pre-clinical trial data can now membranes and is required for that control cellular reactions within our strategies for preventing and slowing thecilium diabetes and hypertension. The multiTaylor’s collaboration with Sigmoid Pharma has successfully secured €485,500 in funding as only enhance the solubility and permeability of One of seven genes associated with JSRDs, to regulate important ciliary membrane development of focus unifiedinapproaches for is on glycosylated. With many specific glycans or inform the next phase Sigmoid Pharma Reference The this publication structure/function both studies worms andproduct progression of the disease. in These will certainly successful by these metrics with own cells. findings research disciplinary research consortium has 25 part of an overall award tocan the the drug butThe deliver itof totheir targeted locations Arl13b codes for aSystems protein already known to large properties such as shape, transmembrane handling scalebeen glycomics data initiatives glycoforms showing potential as cancer development pipeline”. Ligand-specific c-Fosand expression emerges from the understanding how breast cancer cells be integrated with clinical epidemiological mammals demonstrates the remarkable three co-authored publications to date in two of partners (16 universities, 9 industry partners) in the gastrointestinal tract, including the Biology towards Novel Chronic Kidney wereisroles published inand/or Cell. function biomarkers, there an increasing need to with applications biomarker discovery play in the recently formation proteinindistributions and IFT. spatiotemporal control of ErbB network dynamics. studies across the consortium using systems listen toand two In addition to the product that is currently in the highest ranking scientific journals theNIBRT colon.and Treatment evolutionary conservation of how this from 15 countries thedifferent project issignals due tousing runinthis Diseasehigh Diagnosis (SysKid) researchers Dr Campbell and Natalia develop throughput, highly and Nakakuki T, Matthew Birtwistle MR, Saeki Y,Dr Yumoto N, small Ide K, of cilia, which are sensitive hair-like projections biology methodologies in order Sigmoid to develop new is This research was partially supported by phase II clinical studies, Pharma field, Gastroenterology and Proceeding of the ArtemenkoNagashima who developed GlycoExtractor for five years. systems biology approach. One signal consortium underthat thedetail European Union FP7 Up to only 20 years ago, many believed G-protein functions.” robust strategies the glycome of T, Brusch L, Ogunnaike BA, OkadaThe cells infrom our bodies continually listen The Sigmoid Pharma-Taylor collaboration is extending the surface of the cell. diagnostic strategies LEDDS™-enabled and treatment options to developing formulation National Academy ofto Sciences, as well as the programme. HatakeyamaaM, Kholodenko BN. Cell, 2010 Mayof causescilia these cells grow, whereas the most to including be redundant cellular facilitating the development of a new team, postdoctoral for signalsthe in precise their local environment and However, molecular detailsThe of UCD Conway prevent CKD development. Email Reference the hydroxylase inhibitor generation of proprietary innovative products organelles thatthese have fallen victim to other causes cells differentiate. 28;141(5):884-96 therapeutic approach fordoing the treatment ofresearchers Dr. the Craig Slattery and Dr.to Natalia Syskid (www.SysKid.eu) was established toin ciliafor Joubert syndrome for Arl13b functions ciliary tara.mcmorrow@ucd.ie details of aat PhD dimethyloxaloylglycine (DMOG) to bring about creation of high-skilled jobs. then make appropriate decisions proper and what exactly Arl13b is have inflammatoryofbowel disease (IBD) by bringing evolution a type of cellular position effective, These activate or inactive membranes andand stabilizes protein transport in Martin, will mammalian utilise signals cell culture and-animal currentlysafe available. further our understanding chronic kidney targeted delivery of this remained unclear. body functionality. For instance, during More than 15,000 people in Ireland and together the research methodology of the Caenorhabditis elegans. Cevik S, Hori Y, Kaplan OI, appendix. Wesignalling now know that thesewhich cellular subsequent potential, potential therapeutic agent. pregnancy and after childbirth, a woman’s millions of people worldwide are living with the Kida K, Toivenon T, Foley-Fisher C, Cottell D, Katada T, Taylor group withstudied the proprietary Blacque’s team the gene in the cilia antennae present or on nearlyhave all ofbeen our cells when perturbed symptoms IBD today.faulty Current therapeutic body releases hormones that make certain Kontani K, Blacque OE. J Cell Biol. 2010 Mar 22; liquid/emulsion drug delivery system, of tiny worms (Caenorhabditis elegans) and serve fundamental roles in many implicated in the progression of disease numerous options for this chronic debilitating are 188(6):953-69 LEDDS®, developed bythe Sigmoid Pharma. breast cells develop to on the research, Dr Kennedy to die asand a result of the raised including Commenting New research while led bycollaborators Conway Fellow Drcapability in the University ofmost likely very motility sensory functions, types of in cancer. limited with surgery often being the only produce milk; a process termed glucose levels seen diabetes. Breandán Kennedy indicates that treatment said, “By establishing a robust model for early Commenting on theparallel award,experiments Professor Taylor Tokyo conducted in signalling pathways critical to development. viable option. The Sigmoid product, currently of diabetic blindness should look at for Dr Coulter and his and late stage diabetic retinopathy, we would differentiation. said, “We are delighted a phase IIalso clinical study, uniquely enables cultured human cells. Together, they Dr Kennedyin and his team found that new blood This work solves the puzzle of how EUROCarbDB, protecting the neurons responsible for07/05/2010 colour Glycomics needs the supporting framework cells, tissues and fluids. a research infrastructure design to better understand the progression of team and indeed it reflects well on our vessels It is now that defects May 2010.qxd:Layout 1 copy 13:12 Page 3not oral delivery ofsurprising a powerful drug withoutin hope and the neuronal cell death in diabetic confirmed that Arl13b proteins uses lipid vision in the eye and not just targeting the cells have unique responses to of extensive, well-curated and study funded by pave the EU Framework the disease and the6th way for identifying partnership. Adatabases key driver processes of successful cilium structure and function aresignals associated causing systemic side-effects. Such cellular listening are colretinopathy can arise independently of each Commercial packages that support HPLC anchors to associate with the ciliary blood vessels as istools. currently the flexible analytical Currently, thisisfield Programme. Prospective users can treatment”. access the scientific research in practice. 2010 meaningfulother. In addition, drug targets for its successful even when using theextraction same chemical with an ever expanding range ofofhuman new they identified that cone instrumentsUnder cannot facilitate the lectively called signal transduction, and membrane. GlycoExtractor toolprocesses on of study lacks the established, normal conditions, the gastrointestinal interaction withblind industry that disease (CKD) and improve patient treatment, models to identify involved in early Conway ledof byacademia Dr. Taraare reactions to generate them. It reveals how photoreceptor neurons, those involved in Nearly 2.5researchers million people worldwide diseases and syndromes, collectively called large quantities of data. In an effort to alleviate The research was funded through Science a and major challenge in current biomedical comprehensive centralised data http://glycobase.nibrt.ie:8080/DemoGlycoExtra progression and investigate novel McMorrow andretinopathy. Professor Michael have with particular focus on CKD arising from colour and used in daylight, are most due to diabetic This secondary cells rely on precise control of both clinical theCKD this bottleneck within high-throughput Much of and the on Ryan the project was carried ciliopathies, which have overlapping Foundation Ireland and the Health Research collections, standards information ctor/mainPage. research isactivates towork understand theaslanguage of vision strategies for preventing and slowing the diabetes and hypertension. The multisuccessfully of secured €485,500 inthe funding affected by the high glucose levels. complication diabetes growth glycomic projects, the NIBRT team have timing and location of these chemical reout by UCD doctoral candidate, Sebiha features such as polycystic kidneys and Board. reporting protocols that exist within Reference this award listening inthe terms reacprogression of the disease. These studies will disciplinary research consortium has 25 part of leaky an overall Systems of new blood vesselstointhe eye of andthe is chemical developed aactions web-based tool that interfaces to create unique cellular Awith web-based for high GlycoExtractor: genomics and Cevik. proteomics. SheChronic and her colleagues to research livers, degeneration, bone responses The teamretinal made their observations be integrated clinicalinterface occurring within the cell.went onpartners Graphical depiction ofand the epidemiological complex cellular (16 universities, 9 industry partners) Biology towards Novel Kidney responsible fortions the death of photoreceptors, with the Waters chromatography software throughput processing of HPLC-Glycan data using a novel zebrafish model of diabetes, demonstrate in C. elegans how disrupting abnormalities, hydrocephalus, as well as out of seemingly identical chemical reacArl13b at ciliary membrane studies across the consortium using systems biochemical signalling network human from 15 countries and the project is due to run Disease Diagnosis and Treatment (SysKid) the neurons that send visual messages to Reference: package to improve and automate the export Researchers, Dr Natalia Artemenko and Drour Natalia V. Artemenko, Matthew P. Campbell,within and Pauline which resembles the early stages of diabetic biology inResearch, order to2010, develop new breast epithelial cells involving an intricately tion networks. M. Rudd methodologies Journal Proteome brain. for five to years. consortium under the Union FP7 director Professor Kholodenko, deputy of Matthew Campbell fromEuropean the National Institute of data various file formats for subsequent Predominant coneofphotoreceptor dysfunction in9a(4), pp retinopathy in humans. It is an exciting 2037–2041 diagnostic strategies options toloops” arranged cascade of treatment “coherent feedforward hyperglycaemic model of and non-proliferative diabetic of Bioprocessing Research & Training (NIBRT) analysis. The modular architecture of the tool programme. Systems Biology Ireland (SBI), is applying development for the group who now hope to Until now, it was unclear if the changes to The UCD Conway including characterised by the pictured “AND gates”, and prevent CKD development. Email retinopathy. Yolanda Alvarez, Jenneth Chen, Alison alsoof facilitates the team, manipulation ofpostdoctoral data from led by ConwayaFellow, Professor Pauline Rudd systems biology approach The researchers also that further extend and establish a the vessels and neurons occurred independently ofthe feedback, characterised lines ending researchers Dr.their Craig Slattery andfound Dr. Natalia Syskid (www.SysKid.eu) was established to to for details of by aBreandan PhD Meta-analysis by UCD researchers ledtask by of HIV nef are critical in determining the rate studies inresearch humans have shown that non tara.mcmorrow@ucd.ie Reynolds,negative Nore Waghorne, John J. O’Connor, have developed an open access, web-based other data management systems. listening system isand incredibly model late stagecell diabetic disease. one other and which of neuron is Shields Kennedy. with Disease Models &T”Mechanisms (2010) understanding the mechanism cells use a “sideways rather than an arrow.Denis Martin, will utilise culture animal currently available. further our understanding ofretinal chronic kidney Conwaytype Fellow, Professor Denis has of of disease progression. Professor progression was associated withrobust gross to position interface that facilitates extraction, querying The NIBRT team are in now that there is no clear Shields believes that searches for modifiers of deletions theworking nef gene.to integrate and sharing of determined HPLC-glycan data generated in evidence GlycoExtractor with the EUROCarbDB that particular defective viral sequences in progression rates should now focus on other high throughput processes. larger programmes such as the new MSc in We introduced 4 new advanced core Ithe amHIV-1 delighted to welcome you to the However, much of the research in the area to to provide a comprehensive highnef gene or certain regions offramework the host and viral factors. “Systematic evaluation date has been based on case modules onobservational a pilotforbasis or this Conway Focus and look forward to working Imaging commencing in by September 2010. throughput technology HPLC data analysis platform Glycosylation is the most common and role protein play a significant in disease of large quantities of data bioinformatics studies rather systematic the storage academic and annotation of rigorous, experimental structurally diverse post-translational year;than those covering principles progression. can be just as important in refuting with you in the coming months! scientific evaluation. This work by doctoral data. The integration of next generation modification of proteins. More than half of all that are current in initiatives, the literature, as and practical aspects of imaging and Ihypotheses hopelined that awith number of new HIV-infected patients can be categorisedbioinformatic on candidate Ravindra Pushker set the out totheapplied tract cells that block the contents results in both academic outputs andnecessary Irish biopharmaceutical Welcome! of the fluids. Institute and securing Ireland and IDA client companies. We gene products have been shown to bedevelopment tools will further the it is is in adiscovering unknown patterns”, he said. cells, tissues and EUROCarbDB, research infrastructure design Glycomics needs the supporting framework proteomics began in late March and will run the basis of the number of years it takes for determine in a substantially larger sample set As an institute with an increasingly including the early-stage researcher forum of theacknowledge gut from leaking into the intestine. an application research achieving toward product company, Pharma recently scooped glycosylated. manySigmoid specific glycans or development of unified approaches for clinical funding tooffacilitate the also the commitment ofInthe study funded by the EU 6th Framework of extensive, With well-curated databases and until mid-June with a further two modules in them to progress to AIDS. Some patients if any association exists between disease This research was funded through Science IBD patient, in this barrier broken the development withsupport indigenous companies.” the overall Innovation of the Yearand awardhandling at Commercial packages that glycoforms showing potential as large scale glycomics dataHPLC initiatives interdisciplinary research focus described this issue,iscan will not and onlythe Programme. Prospective users access flexible analytical tools. Currently, this field The publication ofcancer this issue coincides ambitions of our research projects. European Commission to research and maintain stable CD4 lymphocyte counts and progression and particular amino acid Foundation Ireland and University College genomics and flow cytometry contents of the gut leak out into surrounding the inaugural Irish Times All-Island instruments cannot facilitate the extractiontaking of place with applications in biomarker discovery biomarkers, there is an increasing need to thof Conway GlycoExtractor tool the on community of study lacks thenot established, expertise specialist technology platforms, strengthen Commenting on the Taylor collaboration, DrNIBRT with preparations to innovation through thein7and EU Framework do go in on to develop AIDS eventhe after more quantities differences thethe nefsummer gene. Dublin. researchers Dr Matthew Campbell Dr Conway Natalia areas. The research team UCD used Innovation Awards. Thecelebrate life-science SME, large of data.orIndeletions an effortwithin to alleviate develop high throughput, highly sensitive and over week-long periods during http://glycobase.nibrt.ie:8080/DemoGlycoExtra comprehensive and centralised data th Coulter said, “The collaboration with the Taylor This research was partially supported by we are placed participate inthis the than 10uniquely years of pharmacology infection. ArtemenkoaProgramme who developed GlycoExtractor researchers and forge new interdisciplinary 10 anniversary of the to UCD Conway We welcome the recent announcement (FP7) and hope to secure theof model of IBD and, by applying a new class founded by UCD graduate, Drbottleneck within high-throughput robust strategies that detail the glycome of On a per patient basis, there was nopotential excess ctor/mainPage. of months. collections, standards and information laboratory clearly demonstrates the drugs known hydroxylase inhibitors, were Ivan Coulter, has actively with glycomic projects, the NIBRT team Festival ofare Research &ofInnovation of continued investment in Irish research opportunities within this work with education and training the links but willascelebrate andto heighten Scientists curious as tocollaborated whynext thesewith longLTNP patients with one orhave more defective nef reporting protocols that exist within that can be realised through focused Reference able to almost reverse the Conway Fellow, Professor Cormac Taylor developed aby web-based toolcompared that with interfaces retrospective of outstanding research the Government, the money research groups across Europe. term, nonprogressor (LTNP) patients not sequences when progressors. generation of research scientists. Thedo newly A web-based interface for high genomics and a proteomics. awareness ofcompletely our research and innovation application basic research. development We hope toof determine fromtoThe this pilot if GlycoExtractor: symptoms disease. data since being granted a Science Foundation with the Waters chromatography software Reference: processingofofthe HPLC-Glycan throughput develop AIDS. This may reflect differences in While the high frequency of amino acid achievements and a showcase of current channelled through the main funding of a smart economy will depend on like-minded launched PhD programme in Bioinformatics successes. Meta-analysis to test the association of HIV-1 nef amino demand for training from within UCD as well Ireland research partnership award Researchers, Dr Artemenko and Dr package to improve andatautomate the exportis indicative Natalia V. Artemenko, Matthew P. Campbell, and Pauline theNatalia host,industry viral genetics or while environmental replacement particular residues weProteome applied these drugs to our IBD collaborative partners identifying opportunities research projects. Even pausing to bodies including Science Foundation Ireland Professor Walter Kolchnew acid differences and deletions with disease progression. M. Rudd “When Journal of Research, 2010, 9 (4), pp and Systems Biology recently 80 in 2004. data to various file formats for subsequent Matthew Campbell from National Institute as from external academic centres and factors thatthe could potentially be attracted exploitedoffor of rapid evolvement, permutation testing Ravindrathe Pushker, Jean-Marc Denis C. Shields. model, gut was trickedJacquē, into thinking that it and realising basic and applied researchin 2037–2041 reflect onTimes the past decade, wefor are firmly (SFI), thethat Programme for Research Director of Bioprocessing & Training (NIBRT) analysis. The modular architecture ofmore the tool Professor Walter Kolch EU and non-EU applicants to 15 The Irish120 recognises theup stellar theResearch treatment ofaward the disease. showed residues with replacements Journal of Virology, Apr 2010 p3644-3653 industry will dictate stand-alone delivery of was being deprived of oxygen. This activated synergies. This collaboration, initiated through led by Conwayinnovative Fellow, Professor Pauline Rudd direction alsoinfacilitates the manipulation ofstatistically data from Enterprise focused on the future strategic Third Level Institutions (PRTLI), performance of Sigmoid Pharma than expected were not significant. advanced modules or inclusion Director, UCD Conway Institute studentships. protective pathways, which in turn prevented athese supplement, highlights thewithin Commenting on the research, Dr Kennedy most toSFI dieresearch as a result of the raised New research led Conway Fellow Dr have shownother Studies in model that likely data management systems. have developedtheir an by open access, web-based application oforganisms research and development. theestablishing death of theacells thatmodel line thefor early potential that innovative indigenous companies glucose levels seen in diabetes. Breandánthat Kennedy indicates that treatment said, “By robust infection with nef-deficient virus shows an The researchers conclude that current data interface facilitates extraction, querying The company has developed two new drug explained academia can realise.” residues The NIBRT working team arewith now working toindividual integrate of diabetic should look at and lategastrointestinal stage diabetic tract,” retinopathy, we Professor would provides no evidence that attenuated course ofgenerated infection and and sharingblindness oftechnologies, HPLC-glycan data in some LEDDS™ and SmPill™, which not Dr Kennedy andwith his the team found that new blood Taylor. “Our pre-clinical trial data can now GlycoExtractor EUROCarbDB protecting the neurons responsible for colour hope to better understand the progression of high throughput processes. Taylor’s collaboration with Sigmoid Pharma has only enhance the solubility and permeability of andtothe vessels neuronal cell death in diabetic inform the next phase Sigmoid Pharma framework provide a comprehensive highvision in the eye and not just targeting the the disease and pave the way for identifying product certainly been successful by these metrics with thethe drug butcommon can deliver it to targeted locations retinopathy can arise independently of each development pipeline”. Glycosylation is most and throughput HPLC data analysis platform for blood vessels as is currently the practice. three co-authored publications to date in twonew of drug targets for its successful treatment”. in thepost-translational gastrointestinal tract, including thethe other. In addition, they identified that cone structurally diverse storage and annotation of experimental In addition to the product that is currently in the highest ranking scientific journals in the colon. photoreceptor neurons, those involved in Nearly 2.5 million people worldwide are blind data. The integration of next generation modification of proteins. More than half of all The research was funded through Science phase II clinical studies, Sigmoid Pharma is field, Gastroenterology and Proceeding of the colour vision and daylight, due toproducts diabetic have retinopathy. This secondary gene been shown to be collaborationbioinformatic toolsused will in further the are most Foundation Ireland and the Health Research The Sigmoid Pharma-Taylor is

Success in EU FP7 call

Zebrafish model gives insights into diabetic blindness GlycoExtractor advances glycan data manipulation Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Director’s Message

Conway collaborator scoops Irish Times Innovation Award Director’s Message GlycoExtractor advances glycan data manipulation

Zebrafish model gives insights into diabetic blindness

UCD CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH


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