Conway Focus Issue 18 Winter 2012

Page 1

Irish biopharmaceutical development New research in Nature Immunology company, Sigmoidprotein Pharma acts recently shows Pellino3 likescooped a the overall Innovation of the Year award at braking system to prevent overthe inaugural Irish Times All-Island production of interferon in response Innovation Awards. The life-science SME, to viral by insult. highlights both a Dr founded UCD This pharmacology graduate, As a Coulter, European Centre of07/05/2010 Excellence, the Ivan actively collaborated with new physiological role for Pellino3 May 2010.qxd:Layout 1has copy 13:12 Conway Fellow, Professor Cormac and a new autoregulatory network Department of Rheumatology in StTaylor Vincent’s since being granted a Science Foundation for controlling type interferon University Hospital was1 chosen to host an Ireland industry research partnership award expression. international two-day workshop on March in 2004.

results in both academic and the of has implications in theoutputs development application of research toward clinical product therapies to tackle debilitating immunedevelopment with indigenous companies.” mediated diseases”, said Professor Commenting on the Taylor collaboration, Dr Callanan.

tract lined metabolome with cells that block the based contents the is faecal differed on of the gut from leaking into the intestine. In an the community setting of the subject and IBD patient, this barrier is broken and the co-varied with measures of frailty. contents of the gut leak out into surrounding areas. The research team in UCD Conway used the by data support a class of a“Collectively, model of IBD and, applying a new relationship diet,inhibitors, microbiota Addressing international guests, Ms Mary drugs known the asbetween hydroxylase were and and reverse indicate a role able tohealth almoststatus, completely Duff, Director of Nursing and Ms.the Kay symptoms of the disease. for diet-driven microbiota alterations Connolly, Assistant Director of Nursing forinthe

Centre of Excellence hosts international workshop

26thIrish & 27th 2010. Sponsored by the Roche The Times award recognises stellar

Conway Professor Sean Callanan innovative performance ofworkshop Sigmoid Pharma Pharma, Fellow, the Participate gave in of UCD School of Veterinary their application of research andMedicine development. twenty rheumatologists from centres in collaborated on the projecttwo lednew by drug The company has developed Europe andPaul Australia the to not technologies, LEDDS™ andopportunity SmPill™, Professor Moynagh, Institutewhich of only enhance the solubility and permeability of witness the care of Maynooth. patients with rheumatoid Immunology, NUI the drug but it to targeted locations arthritis (RA)can at deliver St Vincent’s. in the gastrointestinal tract, including the “Pathology provided a valuable colon.

assessment of the effects of encephalomyocarditis virus in Pellino 3The Sigmoid Pharma-Taylor collaboration is facilitating mice, the development a new deficient enhancingofthe important therapeutic approach treatment of translational aspectsforofthe this work that

Coulter said, “The collaboration with the Taylor

laboratory clearlyprogramme demonstrates the potential Gut microbiota composition correlates The Participate focused on Page 3 realised that can through with dietbeand health in thefocused elderly advanced treatment regimens for RA in the application of basic research. The development according to research published inbiologic Nature including practical aspects ofclinic, a smart economy will depend onoflike-minded involving Conway Dr Lorraine therapy carried out Fellow, inidentifying the accredited infusion collaborative partners opportunities Brennan UCD ofcare Agriculture and realising basicSchool and applied research suite thatofprovides optimal for RA & Food Science. synergies. This collaboration, initiated through patients. In addition to lectures from Conway aFellows, SFI research supplement, highlights and the Professors Oliver FitzGerald

The study, by Dr Paul O’Toole, potential thatled innovative indigenous companies Douglas Veale, delegates heard from clinical working withCollege academia canmeasured realise.” the University Cork nurse microbiota specialists about patient education, faecal composition ofPharma 178 has Taylor’s collaboration with Sigmoid screening and monitoring of biological elderly people with an certainly been successful average by these age metrics with therapies. of 78co-authored years and resident either in the three publications to date in two of community, day-hospital, the highest ranking scientific rehabilitation journals in the or in Gastroenterology long-term residential care. field, and Proceeding of the National Academy of Sciences, as well as the

generation of proprietary innovative products The UCD team performed metabolomic and the creation of high-skilled jobs. analysis of faecal water and showed that

varying rates of health decline on ageing.

“When weJoint applied new drugs ourthat IBD Bone & Unitthese expressed their to hope It alsothe highlights the potential role of model, gut was tricked into thinking that it the experience of the multidisciplinary team metabolomics in of identifying biomarkers was being deprived oxygen. This activated from St Vincent’s would provide a template of healthpathways, and healthy aging”, Dr for protective which in turnsaid prevented delegates reproduce Brennan. the death ofto the cells thatsimilar line thecare and facilities for thetract,” management RA patients in gastrointestinal explainedofProfessor References Taylor. “Our pre-clinical trial data can now their respective countries. Claesson MJnext et al. Gut microbiota composition inform the phase Sigmoid Pharmacorrelates product with diet and health in the elderly. Nature 2012 development pipeline”. doi:10.1038/nature11319 In addition to the product that is currently in phase II clinical Sigmoid Pharma is and Siednienko J et al. studies, Pellino3 targets the IRF7 pathway developing a LEDDS™-enabled facilitates autoregulation of TLR3- andformulation viral-inducedof the hydroxylase expression of type Iinhibitor interferons. Nature Immunology 2012 dimethyloxaloylglycine (DMOG) to bring about 13 (11); doi:10.1038/ni.2429 effective, safe and targeted delivery of this potential therapeutic agent.

Frog peptide structure selectedscoops for journal Conway collaborator Irish cover Times Innovation Award

inflammatory bowel disease (IBD) by bringing together the research methodology of the Taylor group with the proprietary liquid/emulsion drug delivery system, LEDDS®, Sigmoid Pharma.central An image developed of the frogbypeptide structure

Conference Success

Irish biopharmaceutical developmentHewage, Conway Fellows, Dr Chandralal to the workSigmoid a the UCD Conway research team company, Pharma recently scooped Commenting award, Taylor Dr Lorraineofon Brennan andProfessor Professor wasoverall selected as the front cover image forat the said, “We are delighted forpart Dr Year Coulter and his the Innovation of the award Paul Malthouse were of the local April 2010indeed edition of the scientific journal, team and it reflects well on our the inaugural Irish Times All-Island organising the EUROMAR partnership. Acommittee key driver offor successful BiochimicaAwards. et Biophysica Acta (BBA);SME, Innovation The life-science 2012 conference held from 27 June – 5 scientific research in 2010 is meaningful Proteinsby & Proteomics. founded UCD pharmacology graduate, Dr July in UCD. interaction of academia with industry that Ivan Coulter, has actively collaborated with

PeptidesFellow, in the skin of many speciesTaylor of frog Conway Professor Cormac

May

have anti-bacterial and anti-fungal properties EUROMAR is an international scientific since being granted a Science Foundation as well as the ability to advancing lysepartnership or rupture society dedicated to magnetic Ireland industry research award mammalian cells. This850 innate immunityfrom13:12 resonance delegates in 2004. research. 2010.qxd:Layout 1 copy 07/05/2010 protects fromattended attack.recognises These properties of 46 countries plenary lectures, The Irish itTimes award the stellar frog skinlectures, peptides are exciting fromPharma the session tutorial sessions, oral in innovative performance of Sigmoid prospect of being intodevelopment. and poster presentations and scientific their application ofdeveloped research and Meta-analysis by UCD researchers byantitherapeutically valuable anti-infective and The companyTwo has developed two newled drug exhibitions. satellite meetings were Conway Fellow, Professor Denis Shields has cancer agents. technologies, LEDDS™with and SmPill™, which not held in conjunction the conference; determined that there is no clear evidence only particular enhance the solubility andsequences permeability of XeMat and COST Action ‘European that defective viral Conway2012 Fellow, Dr Chandralal Hewage andinhis the drug but deliver it to targeted Network forcan Spin Hyperpolarisation the HIV-1 nef gene or certain regionslocations of the the team carried out molecular modelling of in the gastrointestinal tract,role including the protein play significant inNMR disease Physics andaMethodology andin a XT-7 peptide and its analoguein[G4K]XT-7 colon. progression. MRI’.

More than 15,000 people in Ireland and millions of people worldwide are living with the symptoms IBD today. Current therapeutic options this chronic debilitating disease are varietyinfor ofboth solutions in order to understand the results academic outputs and the only Systems Biology Ireland (SBI) led the by very limited with surgery often being structural basis for the difference in biological application of research toward clinical product Professor Walter Kolch organised SysMed viable option. The Sigmoid product, currently activity. development with indigenous companies.” in a phase II clinical study,conference uniquely enables 2012; an international on oral delivery of a powerful drug place without systems medicine that took in Commenting on the Taylor collaboration, Dr the This particular XT-7 peptide, isolated from causing systemic side-effects.

Carton House from 10- 13 September Coulter “The collaboration with the Taylor skin of said, Silurana tropicalis, shows potential for Under normal conditions, the gastrointestinal 2012. Systems medicine has emerged laboratory clearly demonstrates the potential drug development as it has impressive activity thata can realised through focused as newbe approach personalised against the growth oftobacteria and Candida application ofthat basicuses research. The development health care biological/medical albicans. However, this potential aslike-minded an antiof a smart economy willmathematical depend on data integrated with infective agent is restricted by itsopportunities haemolytic collaborative partners identifying and computational modelling to Page 3 activity. and realising basic and applied research understand the underlying mechanisms synergies. This collaboration, initiated through of disease develop new strategies for change toand the amino acid structure of the aASFI research supplement, highlights the individualised diagnosis, and XT-7 peptide can createindigenous antreatment analogue that potential that innovative companies studies in humans have shown that non prevention. retains anti-infective but without the working with academiaproperties can realise.”

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 symptoms of the disease. SFI Director, Prof Mark Ferguson (left) with Dr

“When we applied these new drugs to our IBD

Chandralal Hewage at EUROMAR 2012. Bioinformatic analysis of HIV progression studies model, the gut was tricked into thinking that it

HIV-infected can be collaboration categorised on The Sigmoid patients Pharma-Taylor is the basis ofthe thedevelopment number of years it takes for facilitating of a new them to progress to AIDS. Some patients therapeutic approach for the treatment of maintain stable CD4 disease lymphocyte and inflammatory bowel (IBD)counts by bringing do not go on to develop AIDS even after more together the research methodology of the than 10 years of infection.

progression was associated with gross complicating haemolytic deletions in the nef gene. activity. The single

Taylor’s collaboration with Sigmoidworkshop Pharma has Additionally, a pre-conference amino acid substitution (glycine replaced by certainly successful by these metrics However,been much of the Health research in the area with to showcased the FP-7 funded lysine) improves the therapeutic potential of of date has been based on observational or two case three co-authored publications to date in ASSET project that uses systems biology thishighest naturally occurring peptide. studies rather than scientific rigorous, systematic the ranking journals in the approaches to improve therapies forof the scientific evaluation. This by doctoral field, Gastroenterology andwork Proceeding childhood cancers. candidate Ravindra setasout to as the National Academy ofPushker Sciences, well determine in a substantially larger sample set

generation of proprietary innovative products if any association exists between disease and the creation of high-skilled jobs. progression and particular amino acid

was being deprived of oxygen. This activated protective pathways, which in turn prevented the death thecritical cells that line the of HIV nefofare in determining the rate gastrointestinal tract,” explained Professor of disease progression. Professor Denis Taylor. pre-clinical trial dataforcan now of Shields“Our believes that searches modifiers inform the next phase Sigmoid Pharma progression rates should now focus onproduct other host and viralpipeline”. factors. “Systematic evaluation development of quantities April 2010 edition of Biochimica et Biophysica ofCover large of data by bioinformatics Acta (BBA); Proteins & Proteomics. Incan addition product that is currently in be justto asthe important in refuting

phase II clinical studies, Sigmoid hypotheses are current in thePharma literature, (L-R) Prof Boristhat Kholodenko, SBI Deputy Director;is as developing a LEDDS™-enabled formulation of it is in discovering unknown patterns”, heProf said. Christina Kyriakopoulou, EC Health Directorate; the hydroxylase inhibitorat SysMed 2012 Walter Kolch, SBI Director This research was funded through Science dimethyloxaloylglycine (DMOG) to bring about Foundation Ireland and University College effective, Dublin. safe and targeted delivery of this potential therapeutic agent.

Launch of Conway postdoctoral & graduate forum More than 15,000 people in Ireland and

Conway collaborator scoops Times Innovation Award Grant Thornton Corporate 5k TeamIrish Challenge Taylor group with the proprietary Scientists are curious as to why these longliquid/emulsion drug delivery system, term, non-developed progressor patients do not LEDDS®, by(LTNP) Sigmoid Pharma. A new fortnightly forum for Conway graduate

Two UCD Conway Institute teams in Irish biopharmaceutical development develop AIDS. This may reflect differences andhost, postdoctoral researchers will in bethe launched company, Sigmoid Pharma recently scooped competed very successfully Commenting on the award, Professor Taylor the viral genetics or environmental the overall Innovation of Year award at in May 2010. Thispotentially initiative will give earlysaid, “We are delighted forthe Dr Coulter and for his factors that could be exploited inaugural Grant Thornton Corporate the inaugural Irish Times All-Island stage researchers the opportunity to talk about the treatment of the disease. team and indeed it reflects well on our 5k Team Challenge around Dublin Innovation Awards. The life-science SME, science and Aissues that concern them in an partnership. key driver of successful Docklands on Thursday, September Studies organisms have shown that foundedinbymodel UCD pharmacology graduate, Dr informal environment with refreshments scientific research in 2010 is meaningful infection with nef-deficient virus shows an 6th 2012. The joint venture between Ivan Coulter, has actively collaborated with interaction of academia with industry that provided! Content for the forum will be attenuated course ofand infection andThornton some Conway Fellow, Professor Cormac Taylor Athletics Ireland Grant since being granted a Science Foundation is designed to encourage social Ireland industry research partnership award running among employees from in 2004. Dublin business communities

The Irish Times award recognises the stellar innovative performance of Sigmoid Pharma in Nearly 450 teams, comprising 1700 their application of research and development. The companycompeted has developed twoevent new drug individuals in the that technologies, LEDDS™ and SmPill™, which not only enhance the solubility and permeability of Meta-analysis by UCD researchers led by the drug but can deliver it to targeted locations Conway Fellow, Professor Denis Shields has in the gastrointestinal tract, including the determined that there is no clear evidence colon.

differences or deletions within the nef gene.

millions peoplebasis, worldwide are living with the On a perofpatient there was no excess of symptoms IBD with today. Current therapeutic LTNP patients one or more defective nef sequences whenchronic compared to progressors. options for this debilitating disease are decided theacademic members but it isand envisaged saw the ‘Conway Tigers’ home results in by both the in While the high frequency ofcoming amino very limited with surgery outputs often beingacid the only that it will include a mix of technology application of research toward clinical product 5th place inatThe the mixed residues category and two replacement particular indicative viable option. Sigmoid product,iscurrently development with indigenous companies.” overviews, informal and formal in research evolvement, permutation testing of Conway finishing 7th place in arapid phase II runners clinical study, uniquely enables seminars, PhD rehearsals and careerDr showed that residues with drug more replacements in the men’s and women’s races. Commenting on the Taylor collaboration, oral delivery of aviva powerful without than expected were not statistically development talks from within and beyond Coulter said, “The collaboration withsignificant. the Taylor causing systemic side-effects. laboratory clearly demonstrates the potential academia. Forum committee members, PhD The researchers conclude that current data Event ambassador; Olympian and former Under normal conditions, gastrointestinal that can be through focused student Mr Thomas Schwarzl provides norealised evidence thatthe individual residues

London Marathon winner Catherina

application of basic research. The development McKiernan said “The ofon thelike-minded event of a smart economy willspirit depend was fantastic. It wasidentifying a welcoming sight collaborative partners opportunities and realising basicrunners and applied research to see so many complete the synergies. This also collaboration, initiated through course, while managing to enjoy a SFI research supplement, highlights the themselves at the same time”. potential that innovative indigenous companies working with academia can realise.”

(thomas.scharzl@ucd.ie and postdoctoral tract is lined with cells that) block the contents Reference: Meta-analysis to Dr test the association HIV-1 nef amino researchers, David Gomez of the gut from leaking into theofintestine. In an acid patient, differences andbarrier deletions with disease progression. IBD this isand broken and the (david.gomez@ucd.ie) Dr Craig Slattery Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields. contents of the gut leak out intosuggestions surroundingfor (craig.slattery@ucd.ie invite Journal of Virology, Apr 2010) p3644-3653 areas. The research team in UCD Conway used the forum schedule. a model of IBD and, by applying a new class of drugs known as hydroxylase inhibitors, were able to almost completely reverse the symptoms of the disease. “When we applied these new drugs to our IBD (L-R) Representing UCD Conway Institute: Claire model, the gut was tricked into thinking that it Robinson, Aidan Boland, Maike Jurgens, Dan Dowling, was being deprived of oxygen. This activated Roisin Neary, Dara Lundon, Paddy O’Leary, Leona protective pathways, which in turn prevented Connolly the death of the cells that line the gastrointestinal tract,” explained Professor Taylor. “Our pre-clinical trial data can now inform phase Sigmoid Pharma of HIVthe nefnext are critical in determining theproduct rate development pipeline”. Professor Denis of disease progression.

Bioinformatic analysis of HIV progression studies

that particular defective viral sequences in

The Sigmoid collaboration is the HIV-1 nefPharma-Taylor gene or certain regions of the facilitating thea development of ainnew protein play significant role disease therapeutic approach for the treatment of progression. inflammatory bowel disease (IBD) by bringing together the research methodology of theon HIV-infected patients can be categorised Taylor group with the proprietary the basis of the number of years it takes for liquid/emulsion drug delivery system, Investing in Your Future them to progress to AIDS. Some patients LEDDS®, developed by Sigmoid Pharma.

maintain stable CD4 lymphocyte counts and

Commenting the award, Professor Taylor do not go on on to develop AIDS even after more said, “We are delighted for Dr Coulter and his than 10 years of infection. team and indeed it reflects well on our Scientists areAcurious as to these longpartnership. key driver of why successful term, non-research progressor (LTNP) patients do not scientific in 2010 is meaningful interaction of academia industry that in develop AIDS. This maywith reflect differences

Taylor’s collaboration with Sigmoid Pharma has studies inbeen humans have shown thatmetrics non with certainly successful by these progression was associated with three co-authored publications to gross date in two of believes searches modifiers deletions the nef scientific gene. InShields addition to the that product that isfor currently in of the highestinranking journals in the progression rates shouldSigmoid now focus on other phase II clinical studies, Pharma is field, Gastroenterology and Proceeding of the However, much of the research in the area to Elaine Quinn host and viral factors. “Systematic evaluation developing a LEDDS™-enabled formulation of National Academy of Sciences, as well as the date has been based on observational or case Communications Education Officer the hydroxylase inhibitor generation of proprietary innovative products of large quantities of data by&bioinformatics studies rather than rigorous, systematic Biomolecular &inBiomedical Research dimethyloxaloylglycine (DMOG) to bring about and the creation of high-skilled jobs.UCD Conway Institute can beofjust as important refuting scientific evaluation. This work by doctoral effective, safethat andare targeted delivery of thisDublin University College hypotheses current in the literature, as More than 15,000 people in Ireland and candidate Ravindra Pushker set out to potential therapeuticunknown agent. patterns”, Belfield, Dublin it is in discovering he said.4 millions of people worldwide are living with the determine in a substantially larger sample set Ireland symptoms IBD today. Current therapeutic if any association exists between disease This research was funded through Science options for this chronic debilitating disease are progression and particular amino acid Foundation Ireland and University College E: elaine.quinn@ucd.ie very limited with surgery often being the only differences orThe deletions within the nef gene. Dublin. T: (+353-1) 716 6706 viable option. Sigmoid product, currently F: (+353-1) 716 6701 in a phase II clinical study, uniquely enables On a per patient basis, there was no excess of oral delivery of a powerful drug without W: www.ucd.ie/conway LTNP patients with one or more defective nef causing systemic side-effects.

sequences when compared to progressors.

Under gastrointestinal While normal the highconditions, frequency the of amino acid

Reference:

Success in EU FP7 call May Issue 101 september 2007 Issue Issue 18,2010 Winter 2012

Conway collaborator scoops Irishand Times Reporting in Nature; controlling good badInnovation bugs Award

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 diabetes and 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 May 2010.qxd:Layout 1 copy(SysKid) 07/05/2010from 13:12 Pageand 3 the project is due to run 15 countries Disease Diagnosis and Treatment 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 cells, tissues and fluids. EUROCarbDB, a research infrastructure design Glycomics needs the supporting framework of extensive, well-curated databases and study funded by the EU 6th Framework Commercial packages that support HPLC Programme. Prospective users can access the flexible analytical tools. Currently, this field instruments cannot facilitate the extraction of GlycoExtractor tool on of study lacks the established, large quantities of data. In an effort to alleviate comprehensive and centralised data http://glycobase.nibrt.ie:8080/DemoGlycoExtra this bottleneck within high-throughput collections, standards and information ctor/mainPage. glycomic projects, the NIBRT team have reporting protocols that exist within Reference developed a web-based tool that interfaces GlycoExtractor: A web-based interface for high genomics and proteomics. with the Waters chromatography software tract is lined cells that block ‘Early thediabetes, contents results in both academic outputs and the Irish biopharmaceutical development throughput processing ofwith HPLC-Glycan data Research by Conway Fellow, Dr Oliver the function of worm Arl13b causes the complex traits including obesity, collaborative project entitled weight gain of 12.2kg among women who Women who choose a low glycaemic package to application improve and automate the and export Researchers, Dr Natalia has Artemenko and Drrecently Natalia V. of Artemenko, Matthew P. and Campbell, Pauline In an the gut from leaking into theand intestine. ofaresearch toward clinical product company, Sigmoid Pharma scooped Blacque revealed new information ciliary membrane to bulge become mental retardation even cancer. Nutrition’ that aims to provide changed to low GI diet. index (GI) diet from early pregnancy will of Proteome Research, 2010, 9 and (4), pp Matthew Campbell from the Nationalof Institute file formats for subsequent IBD patient, this barrier is broken the development with indigenous companies.” M. Rudd Journal the overall Innovation the Year awardofatdata to various about a the gene implicatedof inexcessive Joubert gestamisshapen as well as affecting the ability 2037–2041 of evidence-based for reduce likelihood analysis. The modular architecture of the tool of Bioprocessing &Irish Training contents ofBlacque the gutrecommendations leak outthat intothese surrounding theResearch inaugural Times(NIBRT) All-Island Dr Oliver hopes findings models to identify processes involved in early disease (CKD) and improve patient treatment, Conway researchers led by Dr. Tara Commenting onon Taylor collaboration, Dr syndrome and related cerebellar other totheproperly distribute within optimal nutrition that incorporates Commenting the findings, Professor gain and maternal glucose led by Conwaytional Fellow,weight Professor Pauline Rudd disorders also facilitates theproteins manipulation of data from areas. Theearly research team in UCD Conway used Innovation Awards. The life-science SME, will ultimately lead to a greater CKD progression and investigate novel McMorrow and(JSRDs), Professor Michael Ryan with particular focus on CKD arising from Coulter said, “The collaboration with the Taylor by have bone the ciliary membrane. other systems. have developed an openbycharacterised access, web-based health Health McAuliffe said, “Excessive weight gain along-term model of IBD and,outcomes. by applyingWorld a new class founded UCD pharmacology graduate, Dr data management intolerance according to ablindness, research study understanding not of JSRDs, alsoof laboratory clearlyThe demonstrates the potentialstrategies for preventing andonly slowing the butwere diabetes and hypertension. multisuccessfully €485,500 inquerying funding as abnormalities, cystic kidneys, interface that secured facilitates extraction, drugs known asstatistics hydroxylase inhibitors, Ivan Coulter, haswomen actively collaborated with Organisation instudies 2010 highlighted during pregnancy is associated with an involving 800 attending the The NIBRT team are now working to integrate They also found that a fully functional of closely related ciliopathies such as that can be realised through focused progression of the disease. These will disciplinary research consortium has 25 partsharing of an overall award to the Systems and of developmental HPLC-glycan data generated in of Taylor able to almost completely reverse the were Conway Fellow, Professor delay andCormac loss muscle 43 million children under five years increased need for delivery by National Maternity Hospital, Dublin. GlycoExtractor withprotein the of EUROCarbDB basic research. Arl13b needed forThe thedevelopment normal be integrated Meckel Gruber Bardet-Biedl syndrome, with clinical and epidemiological high throughput processes. symptoms of theand disease. since being granted a Science (16application universities, 9isindustry partners) Biology towards Novel Chronic Kidney tone and control. The findingsFoundation of thispartners framework of to provide a comprehensive highoverweight. Childhood obesity predisposes Caesarean section, a higher likelihood of a smart economy will depend on like-minded functioning of a protein transport system in as well as perhaps more common studies across the consortium using systems Ireland industry research partnership award from 15 countries and the project is due to run Disease Diagnosis and Treatment (SysKid) research, funded through Science throughput collaborative HPLCpregnancy data analysis platform foropportunities Glycosylation is the most common and aFionnuala “When we applied new drugsdiseases our IBD partners identifying individuals to other childhood post weight retention, and abiology methodologies Conway Fellow, Professor in 2004. in these order to develop cilia. This intraflagellar transport system phenotypes associated with ciliumtonew for years. consortiumdiverse under the European FP7 of Ireland Foundation IrelandUnion President structurally post-translational the five storage andrealising annotation ofand experimental model, the gut was tricked into thinking that it and basic applied research and premature death. Being overweight higher predisposition to obesity in later life. McAuliffe led the randomised control trial diagnostic strategies and treatment options to (IFT) makes contact with theinitiated ciliary through dysfunction such as and The Irish Times recognises stellar programme.ofYoung data. The integration of next generation modification proteins. Moreaward than half of(PIYRA) all the to was being deprived of mental oxygen. retardation This activated synergies. This collaboration, Researcher Award Oliver The UCD Conway team, including postdoctoral and obese is the 5thwhich leading risk for deaths development. of 800 women without diabetes on their innovative performance Sigmoid Pharma in on results, the they prevent CKD obesity. gene products Blacque, have been shown to beofpublished bioinformatic tools will Based further thethese protective pathways,Email in turn prevented amembrane. SFI research supplement, highlights were recently in the researchers Dr. and indigenous Dr. Natalia Syskid (www.SysKid.eu) was established to development. their many application of research and tara.mcmorrow@ucd.ie for details ofthe a PhD globally. This research hasworking shown that switching to second pregnancy who previously delivered proposed aSlattery new model for Arl13b, glycosylated. With glycans or development of Craig unified approaches for the death of the cells that line potential that innovative companies Journal of specific Cell Biology. He notes “That Arl13b associates with ciliary Theinfant company two 4kg. new drug Martin, culture and animal position gastrointestinal currently available. further our understanding ofhas chronic kidney glycoforms showing potential asdeveloped cancer handlingwill large scale glycomics initiatives autilise low GI diet in pregnancy is a membrane simple, safe tract,” explained Professor working with academia can realise.” where itcell functions atdata the ciliary an weighing more than technologies, LEDDS™ andto SmPill™, which membranes and is required for cilium withnot applications in biomarker discovery biomarkers, there increasing Taylor. “OurNutrition’ pre-clinical trial data can now The ‘Early project teams, including & effective measure to improve maternal Oneisofanseven genes need associated with JSRDs, to regulate important ciliary membrane Taylor’s collaboration with Sigmoid Pharma has researchers only enhance the solubility and permeability of NIBRT Dr Matthew Campbell and Dr Natalia structure/function in both worms develop high throughput, highly sensitive and inform the next phase Sigmoid Pharma product Arl13b codes fordeliver a protein already known toresearch properties such as shape, transmembrane 30 academic partners, 3 industryand partners glucose homeostasis and reduce 400 women continued to follow their This was partially supported by certainly been successful by these metrics with Artemenko who developed GlycoExtractor the drug but can it to targeted locations robust strategies that detail the glycome of development pipeline”. mammals demonstrates the remarkable play in thepattern formation and/or function protein distributions and IFT. to date in two of and 4 small-medium enterprises, are gestational weight gain.” three co-authored publications normal dietary throughout the in theroles gastrointestinal tract, including the evolutionary conservation ofishow this small In addition to the product that currently in the highest ranking scientific journals in the of cilia, which are hair-like projections colon. exploring current key hypotheses on the pregnancy without being given any specific Up to only 20 years ago, many believed G-protein functions.” phase II clinical studies, Sigmoid Pharma is field, Gastroenterology and Proceeding of the extending from the surface of the cell. likely cases and pathways of early programGestational weight gain is one of several advice on gestational weight gain. The Sigmoid Pharma-Taylor collaboration is most cilia to be redundant cellular developing a LEDDS™-enabled formulation of National Academy of Sciences, as well as the However, molecular details of Reference ming of obesityinhibitor risk. factors influencing infant birth weight. facilitating the the precise development of a new the hydroxylase generation of proprietary innovative productsEUROCarbDB, organelles that have fallen victim to cells, tissues and fluids. asyndrome research infrastructure design Glycomics needs the supporting framework Joubert Arl13b functions at ciliary what exactlyapproach Arl13b is in cilia have therapeutic fordoing the treatment of Macrosomic or ‘large for gestational age’ 400 women attended a dietary education dimethyloxaloylglycine (DMOG) to bring and the creation of high-skilled jobs. mammalian evolution a type of cellular membranes and stabilizes protein transport in about of extensive, well-curated databases and study funded by the EU 6th Framework remained unclear. inflammatory bowel disease (IBD) by bringing packages that support infants areWe predisposed to a variety of Programme. effective, safe elegans. and targeted delivery ofthe thisOI, session with the research dietician atCommercial 16 Caenorhabditis Cevikcan S, Hori Y, Kaplan appendix. now knowHPLC these cellular flexible analytical tools. Currently, this field Prospective users access Reference: More than 15,000 people inthat Ireland and together the research methodology of the potential therapeutic agent. instruments facilitate the extraction ofoutcomes, the research, Dr Kennedy tocannot die asobstetric a result of the raised New research Blacque’s led by to Conway Fellow Dr Kida K,on Toivenon C, Cottell D, Katada T, adverse and neonatal inform them of healthy eating team studied thethe gene in themost cilia likely millions antennae on nearly all of ourwith cellsCommenting of study lacks weeks the established, GlycoExtractor tool on T, Foley-Fisher ofpresent people worldwide are living the Taylor group withthat the treatment proprietary Walsh, McGowan, Mahony, ME glucose levels inlikely diabetes. Breandán Kennedy indicates Kontani K, CBlacque OE. JRCell Biol. 2010 Mar 22; said, “ByJM establishing a robust model forFoley, early large quantities of data. Intoday. an to alleviate areseen more to effort beCurrent obese in childhood, guidelines in pregnancy andsystem, encourage symptoms IBD therapeutic http://glycobase.nibrt.ie:8080/DemoGlycoExtra comprehensiveof and centralised data tiny worms (Caenorhabditis elegans) and serve fundamental roles in many liquid/emulsion drug delivery Low glycaemic indexwe dietwould in pregnancy of diabetic blindness should look at 188(6):953-69 and lateFMcAuliffe. stage diabetic retinopathy, this bottleneck within high-throughput adolescence and early adulthood and are at options for this chronic debilitating disease are them to choose low glycaemic index foods Dr Kennedy and his team found that new blood collections, standards and information ctor/mainPage. LEDDS®, developed by Sigmoid Pharma. collaborators in for the colour University of motility and sensory functions, including hope to to prevent macrosomia (ROLO study): randomised protecting the while neurons responsible better understand the progression of glycomicand projects, therisk NIBRT team often have very limited with surgery the only vessels neuronal cell death in diabetic control trial. BMJ 2012;345:e5605 doi:10.1136/bmj. athe greater of cardiovascular & metabolic reporting protocols that exist within such as high fibre cereal and brown rice Tokyo conducted parallel in signalling pathways critical tobeing development. Reference vision in the eye and not just targeting the the disease and pave the way for identifying Commenting on the award,experiments Professor Taylor developed a web-based tool that interfaces viable option. The Sigmoid product, currently retinopathy can arise independently of each e5605A(30 August 2012) GlycoExtractor: web-based interface for high genomics and cultured proteomics. complications later in life. without reducing their calorie intake. This human cells. Together, theyand blood vessels as is“We currently the practice. said, are1delighted Dr Coulter his drug targets for its successful treatment”. with the chromatography software May 2010.qxd:Layout copy for07/05/2010 13:12 3not in a phase II identified clinical study, uniquely enables other. In Waters addition, they that cone It Page is now surprising that defects in new throughput processing of HPLC-Glycan data confirmed that Arl13b proteins uses lipid group had two follow up sessions at 28 and team and indeed it reflects well on our oral delivery of a powerful drug without Researchers, Dr Natalia package to cilium improve and those automate the export Natalia V. Artemenko, Campbell, and Pauline photoreceptor neurons, inare associated Nearly 2.5 million peopleArtemenko worldwideand are Dr blind structure andinvolved function research was Matthew funded P.through Science partnership. AThis key driver of the successful However, this study that a low The anchors associate with ciliary 34 weeks gestation to reinforce this colour lowdata GI vision M. Rudd Journal of Proteome Research, 2010, 9 (4), pp causing systemic side-effects. andanused inexpanding daylight, are most due to diabetic retinopathy. secondary Matthew Campbell fromtothe National Institute of to various file formats forshowed subsequent Foundation Ireland and the Health Research with ever range of human scientific research in 2010 is meaningful 2037–2041 glycaemic index diet inofpregnancy not diet regimen. affected themodular high glucose levels. complication ofmembrane. diabetes activates the growth of Bioprocessing Research & Training (NIBRT) analysis.by The architecture the tool did Board. to identify processes involved in early Under conditions, the gastrointestinal diseases and syndromes, collectively called interaction academia industry that disease (CKD) andnormal improve patientoftreatment, models Conwayleaky researchers ledof byin Dr. of blood vessels theTara eye with andRudd is reduce the incidence ‘large for lednew by Conway Fellow, Professor Pauline also research facilitates the manipulation of data from The team made their observations Much of the work on the project was carried ciliopathies, which have overlapping clinical CKD progression and investigate novel McMorrow and Professor Michael Ryan have with particular focus on CKD arising from responsible for the death of photoreceptors, gestational age’ infants in a group of strategies for preventing and slowing the of theweb-based research, published in data have developedThe an findings open access, other management systems. using a novel zebrafish ofmultidiabetes, and hypertension. outsend by UCD doctoral features suchmodel asThe polycystic kidneys and Reference: successfully secured €485,500 in candidate, funding the neurons that visual messages to ourasSebihadiabetes interface that facilitates extraction, querying women atconsortium riskdegeneration, of foetal the British Journal, showed an which resembles the early stages of macrosomia. diabetic progression of the disease. These studies will disciplinary research has 25bone part of an overall award to the Cevik. She Medical and herSystems colleagues went on to NIBRT livers, retinal brain. The team are now working to integrate Predominant cone photoreceptor dysfunction in a and sharing of HPLC-glycan data generated in retinopathy in humans. It is an exciting be integrated model with clinical and epidemiological average gain of 13.7kg among partners (16abnormalities, universities, 9hydrocephalus, industry partners) Biology towards Novelweight Chronic Kidney hyperglycaemic of non-proliferative diabetic demonstrate in C. elegans how disrupting as well as Arl13b at ciliary membrane GlycoExtractor with the EUROCarbDB development forresearch the group who now hope torun and Until now,Diagnosis it was unclear if the changes high throughput processes. studies across theAlvarez, consortium systems This by Professor McAuliffe retinopathy. Yolanda Jenneth using Chen, Alison 15 countries and the project is due to women remained ontotheir usualfrom diet Disease andwho Treatment (SysKid) framework to provide a comprehensive highfurther their research and establish a vessels and neurons occurred independently biology in order to develop new Reynolds,methodologies Nore Waghorne, John J. O’Connor, Breandan for five extend years. consortium under the European Union FP7 of an average her team is part of a wider EU FP7 funded during their pregnancy, against throughput HPLC data analysis platform for Glycosylation is the most common and model of late stage diabetic disease. one other and which type of retinal neuron is Kennedy. Disease Models and & Mechanisms diagnostic strategies treatment(2010) options to programme. structurally diverse post-translational the storage and annotation of experimental The UCD Conway team, including postdoctoral prevent CKD development. Email modification ofMeta-analysis proteins. More than oftoall led researchers data. The integration next generation Dr. Craig Slattery and Dr. Natalia Syskid (www.SysKid.eu) wasby established for details of a PhD the rate UCDhalf researchers by of HIV nef are critical in determining studies in of humans have shown that non tara.mcmorrow@ucd.ie gene products have been shown to bekidney bioinformatic toolscell willculture further the animal Martin, utilise and position currently further our understanding of chronic Conway Fellow, Professor Denis Shields has will progression of diseaseavailable. progression. Professor Denis was associated with gross glycosylated. With many specific glycans developmentdeletions of unified approaches determined that there is no or clear evidence Shields believes that searches for modifiers of in the nef gene. for viral you sequences in progression rates should focus onMSc otherin larger programmes suchnow as the new We scale introduced 4 new advanced core Ithat amparticular delighted to welcome to thehandling large glycomics data initiatives glycoforms showing potentialdefective as cancer However, much of the research in the area to the is HIV-1 nef gene certain ofwith the applications host and commencing viral factors. “Systematic evaluation in biomarker discovery biomarkers, there an Focus increasing need to regions technology modules onobservational a pilot basis or this Conway andorlook forward to working Imaging in September 2010. date has been based on case protein playhighly a significant role in disease of largeDrquantities of data by Matthew Campbell andbioinformatics Dr Natalia develop high throughput, sensitive and academic year;than those covering principlesNIBRT researchers studies rather rigorous, systematic with you in the coming months! This research was partially supported by progression. just asGlycoExtractor important in refuting Artemenko can who be developed robust strategies that detail the glycome of scientific evaluation. This work by doctoral and practical aspects of imaging and applied Ihypotheses hope that athat number of new initiatives, current inInstitute thethe literature, tract isaligned lined with cells that block contents results in bothsessions academicfocused outputs on andindustry the Irish biopharmaceutical development Welcome! open forum areas toare that of the will as HIV-infected patients can be categorised on candidate Ravindra Pushker set out to will run proteomics in late March and it the is ingut unknown patterns”, heInsaid. of from leaking into the intestine. an application ofbegan research toward clinical product company, Sigmoid recently scooped tissues As an institute withPharma an increasingly including the early-stage researcher forum and fluids. EUROCarbDB, adiscovering research infrastructure design Glycomics needs framework engagement gender issues impacting undoubtedly provide valuable critique the the basissupporting of the number of years it takescells, for determine in aand substantially larger sample set until mid-June with a furthercompanies.” two modulesstudy in funded IBD patient, this barrier is will broken and the development with indigenous the overall Innovation of and the Yearand award at by the EU 6th Framework of extensive, well-curated databases interdisciplinary research focus described in this issue, not only The quarter has been a busy time for early career researchers. More detail on the of our research and innovation strategy themlast to progress to AIDS. Some patients if any association exists between disease This research was funded through Science packages that support HPLC contents of the gutusers leak out surrounding the inaugural Irish Times Programme. Prospective caninto access the flexible analytical tools. Currently, thisAll-Island field counts Commercial genomics and flow taking maintain stable lymphocyte and progression particular amino acid place Foundation Ireland and University College Commenting onread the Taylor Dr expertise inAwards. specialist platforms, event can beand incytometry thiscollaboration, issue. Institute. I CD4 congratulate all those who as wellThe as research recommendations on futureused instruments cannot facilitate the extraction of strengthen the of Conway areas. team in UCD Conway Innovation Thetechnology life-science SME, of study lacks the thenot established, GlycoExtractor tool on community over week-long periods during the summer do go on to develop AIDS even after more differences or deletions within the nef gene. Dublin. Coulter said, “The collaboration with the Taylor large quantities of data. In an effort to alleviate participated in the annual UCD Conway direction. we are uniquely placed to participate in the a model of IBD and, by applying a new class of founded by UCD pharmacology graduate, Dr researchers and forge new interdisciplinary comprehensivethan and10centralised data http://glycobase.nibrt.ie:8080/DemoGlycoExtra years of infection. months. laboratory clearly demonstrates the potential this high-throughput drugs known as hydroxylase inhibitors, were Ivan Coulter, has actively collaborated with bottleneck Festival of Research &ofInnovation Members of the newly constituted On awithin per patient basis, there was no excess ctor/mainPage. of collections, standards and information education and training the next onglycomic links but will celebrate and heighten that can the be realised through focused projects, NIBRT to almost completely reverse the Conway Fellow, Professor Taylor Scientists are curious to Cormac why these longLTNP patients with team one orhave more defective nef reporting protocols that exist within Referenceable September 20th andasespecially the 2012 scientific advisory board forThe the Institute Professor Walter Kolch generation of research scientists. The newly application of basic research. development awareness of our research and innovation developed a web-based tool that interfaces Commenting on the research, Dr Kennedy most likely to die as a result of the raised New research led by Conway Fellow Dr We hope towhen determine fromtothis pilot if GlycoExtractor: symptoms of the interface disease.for high since beingprogressor granted a (LTNP) Sciencepatients Foundation term, nondo not sequences compared progressors. A web-based genomics and UCD proteomics. Conway Festival medal winner,award met Conway Fellows and representatives of aseen smart economy willsoftware depend on like-minded with Waters chromatography Reference: launched PhD This programme in Bioinformatics glucose diabetes. Breandán Kennedy indicates that treatment processing of HPLC-Glycan data for early throughput said, “ByDirector establishing a robust model successes. Ireland industry research partnership develop AIDS. may reflect differences in the levels While thein high frequency ofwithin aminoUCD acid as well demand for training from “When we applied these new drugs to nef ouramino IBD collaborative partners identifying opportunities Meta-analysis to test the association of HIV-1 Kate Byrne. In addition to celebrating of their research teams during the course Researchers, Dr Natalia Artemenko and Dr package to improve and automate the export V. Artemenko, Matthew P. Campbell, and Pauline Natalia of diabetic blindness should look atrecently in lateJournal stage ofdiabetic retinopathy, we would the2004. host, viral Biology genetics or environmental replacement at particular residues is indicative and Systems attractedDr80Kennedyand as from external academic centres and and acid differences and deletions with disease progression. M. Rudd Proteome Research, 2010, 9 (4), pp that it model, the gut was tricked into thinking realising basic and applied research and his team found that new blood Matthew Campbell from the National Institute of data to various file formats for subsequent the achievements of Conway researchers of the first meeting on October 8th & protecting the EU neurons responsible for colour factors that could potentially be exploited for of rapid evolvement, permutation testing hope to better understand the progression of TheResearch Irish120 Times awardapplicants recognises theup stellar Ravindra Pushker, Jean-Marc Jacquē,This Denisactivated C. Shields. 2037–2041 Professor Walter Kolch and non-EU for to 15 and industry will dictate stand-alone delivery of was being deprived of oxygen. synergies. This collaboration, initiated through analysis. The modular architecture of the tool of Bioprocessing & (NIBRT) vessels the neuronal cell death inmore diabetic in previous year, the programme 9th in the This group of leading thethe treatment ofTraining the disease. showed thatInstitute. residues with replacements Journal Virology, Apr 2010 p3644-3653 vision in the eye and notperformance just targeting the innovative of Sigmoid infacilitates the disease andofpave the way for identifying protective pathways, which in turn prevented athese SFIthe research supplement, highlights thewithin led by Conwaystudentships. Fellow, Professor Pauline Rudd Pharma also manipulation ofstatistically data from significant. advanced modules or inclusion Director, UCD Conway Institute retinopathy can arise independently of each than expected were not to incorporate two dedicated international scientistsindigenous from research blooddeveloped vessels expanded asanisopen currently the practice. their application oforganisms research and new drug forthe itscells successful thetargets death of that linetreatment”. the potential thatidentified innovative Studies in model havedevelopment. shownother that data have access, web-based management systems.that other. In addition, they cone companies The company has developed two shows new drug gastrointestinal tract,” explained Professor working with academia canthat realise.” infection with nef-deficient virus an Theneurons, researchers conclude current data interface facilitates extraction, querying photoreceptor those involved in Nearly 2.5that million people worldwide are blind Thenot NIBRT team are no now working toindividual integrate residues LEDDS™ and SmPill™, which The research through Taylor.was “Ourfunded pre-clinical trial Science data can now provides evidence that attenuated course infection and and sharing of technologies, HPLC-glycan dataofgenerated in some colour and used daylight, most Pharma Foundation due to diabeticonly retinopathy. This secondary Taylor’s collaboration withare Sigmoid has GlycoExtractor with the in EUROCarbDB enhance the solubility and permeability of vision Ireland andphase the Health Research inform the next Sigmoid Pharma product high throughput processes. successful affected by certainly theprovide highbeen glucose levels. by these complication ofthe diabetes activates the itgrowth framework to a comprehensive high-metrics with drug but can deliver to targeted locations Board. development pipeline”. publications Glycosylation isinthe most common and HPLCco-authored data analysis platform to fordate in two of thevessels gastrointestinal tract, thethroughput three of new leaky blood in the eye andincluding is

Worm research reveals cilia geneInnovation functionAward Conway collaborator scoops Irish Times Benefits of Low GI Diet indisease Pregnancy

Success in EU FP7 call

GlycoExtractor advances glycan data manipulation

Zebrafish model gives insights into diabetic blindness

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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Conway Focus Issue 18 Winter 2012 by UCD Conway Institute - Issuu