Conway Focus Issue 14 Summer 2011

being differentially expressed in both protein changes in psychotic disorders Centre of Excellence hosts international workshop disorders.

These proteins are implicated and may provide valuable information

The detailed research study of Irish first biopharmaceutical development protein changes within the company,expression Sigmoid Pharma recently scooped the overall Innovation of the Year award hippocampus in schizophrenia and at the inaugural Irish has Times All-Island bipolar disorder not only shown Innovation Awards. The life-science SME, striking overlap of changes betweenDr founded by UCD pharmacology graduate, As a European Centre of Excellence, the disorders but localised altered with Ivan Coulter, has actively collaborated Department of Rheumatology in St Vincent’s expression to specific subregions in Conway Fellow, Professor Cormac Taylor University Hospital was chosenFoundation to host an since being granted a Science this part of the brain.

results in both academic outputs and the application of research toward clinical product development indigenous companies.” in a range ofwith different processes including

tract is lined with cells that block the contents of the gut from leaking into the intestine. In an IBD patient, barrier ismolecular broken and the about the this underlying contents of the gut leak out into surrounding mechanisms in these illnesses,’ said Dr areas. The research team in UCD Conway used Melanie Föcking. a Addressing model of IBD by applying a newMs class of theand, international guests, Mary drugs known asof hydroxylase inhibitors, Duff, Director Nursing and Ms. Kay were able toproteomics almost completely reverse The research was the conducted Connolly, Assistant Director of Nursing for the symptoms of the disease. in collaboration with Conway Fellow,

cytoskeletalon and functions.Dr Commenting themetabolic Taylor collaboration, Coulter said, “The collaboration with the Taylor The Participate programme focused on laboratory clearly demonstrates the potential Subsequent validation workfor carried out advanced regimens RA in the that canresearchers be treatment realised through focused by the confirmed changes clinic, including practical aspects of biologic application of basic research. The development in athe cytoskeletal protein, septin11 out in accredited infusion oftherapy smartcarried economy willthe depend on like-minded Bone & Joint Unit expressed their hope that international two-day workshop on March Ireland industry research partnership award and proteins involved in the membrane Professor Michael Dunn “When we applied newwhile drugsProfessor to our IBD collaborative partners identifying opportunities suite that provides optimal care for RA the experience ofthese the multidisciplinary team in 2004.

26th & 27th 2010.

Sponsored by Roche The findings by a research collaboration trafficking process of clathrin-mediated Davidthe Cotter led tricked the research in RCSI model, gut was into thinking that it and realising basic and applied research patients.

In addition to lectures from Conway from St Vincent’s would provide a template for The Irish Times awardCollege recognises the stellar Pharma, the workshop gave was deprivedHospital. of oxygen.

This activated synergies.

Thisincollaboration, initiated through involving theParticipate Royal of Surgeons endocytosis bothOliver disorders. andbeing Beaumont The work was Fellows, Professors FitzGerald and innovative performance of Sigmoid Pharma in delegates to reproduce similar care and protective pathways, which in turn prevented a SFI research supplement, highlights the twenty rheumatologists from centres in in Ireland (RCSI), Beaumont Hospital funded by the Wellcome Trust, NARSAD Douglas that Veale, delegates heard from clinical their application of research and development. the death of that line the potential innovative indigenous companies facilities forthe thecells management of RA patients in and UCD Conway Proteome The hippocampus is subdivided into Europe and Australia the07/05/2010 opportunity to 13:12 working and the Stanley Medical Research The company developed twoResearch new drug nurse specialists about patient education, May 2010.qxd:Layout 1has copy Page 3 academia gastrointestinal tract,” explained Professor with can realise.” their respective countries.

Centre published inSmPill™, the May issue not specific regions; cornu ammonis technologies, LEDDS™ and which Institute. witnesswere the care of patients with rheumatoid screening and monitoring of biological Taylor.

“Our pre-clinical trial data can now Taylor’s collaboration with 4 Sigmoid only enhance solubility and permeability of Archives Psychiatry, the of (CA) regions 1 through and thePharma has inform the next phase Sigmoid Pharma product therapies. arthritis (RA)inthe atGeneral St Vincent’s. certainly successful by these metrics the drug ranking but can deliver to the targeted highest journalit in field.locations dentatebeen gyrus.

These subregions differwith development pipeline”. three co-authored publications to date in two of in the gastrointestinal tract, including the anatomically, functionally and in InReference: addition to the product that is currently in the highest ranking scientific journals their in the colon. vulnerability to neurological disorders.

Abnormalities in the hippocampus are phase II clinical studies, Sigmoid Pharma is field, Gastroenterology and Proceeding of the The Sigmoid Pharma-Taylor collaboration Common Proteomic Changes in the formulation Hippocampus of The most prominent proteinaschanges among the most consistent findings is developing a LEDDS™-enabled National Academy of Sciences, well as the facilitating the development of a new in Schizophrenia Bipolar Disorder and Particular the hydroxylaseand inhibitor generation innovative products seen wereofinproprietary regions CA2 and CA3. in schizophrenia research and are also therapeutic approach for the treatment of Evidence for Involvement of Cornu Ammonis dimethyloxaloylglycine (DMOG) to bringRegions about and the creation of high-skilled jobs. implicated bipolar disorder.

2 and 3. Melanie Föcking, Patrick Dicker, Jane A. inflammatoryinbowel disease (IBD)Using by bringing effective, safe and targeted delivery of this mass spectrometry, the researchofteam ‘These results give us greater insight More than 15,000 people in Ireland and into English, K.therapeutic Oliver Schubert, Michael J. Dunn, David R. together the research methodology the potential agent.

Cotter. Arch Gen Psychiatry. 2011;68(5):477-488 millions of people worldwide are living with the Taylor group with the proprietary identified 152 proteins, with 61 of these the nature and extent of region-specific symptoms IBD today.inCurrent liquid/emulsion An image of thedrug frogdelivery peptidesystem, structure central variety of solutions order totherapeutic understand the options for this chronic debilitating disease are LEDDS®, developed Sigmoid Pharma.team to the work of a UCDbyConway research structural basis for the difference in biological very limited with surgery often being the only was selectedon asthe theaward, front cover image for the Commenting Professor Taylor activity. viable option. The Sigmoid product, currently said, delighted forscientific Dr Coulter and his April “We 2010are edition of the journal, in a phase II clinical study, uniquely enables Thisdelivery particular peptide, isolated from the team and indeed it reflects well our Biochimica et Biophysica Actaon (BBA); oral of aXT-7 powerful drug without partnership. A key driver of successful skin of systemic Silurana tropicalis, shows potential for causing side-effects.

Proteins & Proteomics. scientific research in 2010 is meaningful drug development as in it has impressive activity Professor Joeconditions, Duffy the Under normal the Education gastrointestinal Dr Patricia McGowan was awarded tract is lined with cells that block the contents results in both academic outputs and the & Irish biopharmaceutical development interaction academia with industry that Peptides inofthe skin of many species of frog against theCentre, ofVincent’s bacteria and Candida Research St University of the gut from leaking into the intestine. In an application ofgrowth research toward clinical product company, Sigmoid Pharma recently scooped joint first prize from the TIDA / SFI have anti-bacterial and anti-fungal properties IBD patient, this barrier is broken and the development with indigenous companies.” the overall Innovation of the Year award at albicans.

However, this potential as an anti‘Get Started’ Technology Venture May 2010.qxd:Layout copy 07/05/2010 13:12 Hospital.

Page 3Her winning elevator pitch as well as the1Irish ability to lyse rupture contents of the gut leak out into surrounding the inaugural Times All-Island focused an innovative product Programme organised byorScience infective on agent is restricted by its haemolytic Commenting on the Taylor collaboration, Dr mammalianAwards. cells.

This innate immunity areas. The research team in UCD Conway used Innovation The life-science targeted at “The the treatment of with triplethe Taylor Foundation Ireland (SFI) and theSME, Irish activity.said, Coulter collaboration protects by it from attack.

These properties ofDr a model of IBD and, by applying a new class of founded UCD pharmacology graduate, negative breast cancer that may have Technology Leadership Group (ITLG). laboratory clearly demonstrates the potential drugs known as hydroxylase inhibitors, were Ivan Coulter, has actively frog will skin peptides are exciting from the with potential inrealised theamino clinical setting.

A change the acid structure of the She participate in acollaborated week-long visit that can beto through focused able to almost completely reverse the Conway Professor Cormac Taylor prospectFellow, of the beingITLG developed intomembers hosted by to meet application of basic research.

The development XT-7 peptide can create an analogue that symptoms of the disease. since being granted a Science Foundation therapeutically anti-infective and antiof the venturevaluable community and leading of a is smart economy will depend with on SFI working in partnership retains anti-infective properties butlike-minded without the Ireland industrybyresearch partnership Meta-analysis UCD researchers ledaward by of HIV we nefapplied are critical in new determining studies in humans have shown that non “When these drugs tothe ourrate IBD collaborative partnerson identifying opportunities technology companies in Silicon cancer Enterprise Ireland the Technology in 2004.agents. complicating haemolytic activity.

The single Conway Fellow, Professor Denis Shields has of disease progression.

Denis progression was with gross model, the gut was trickedProfessor into thinking that it and realising Development basicassociated and applied research Valley, California.

Innovation Award (TIDA) to determined that there is no clear evidence deletions in the nef gene.

Shields believes that searches for modifiers The Irish Times award recognises the stellar amino acidThis substitution (glycine replaced Conway Fellow, Dr Chandralal Hewage and his was being deprived of oxygen. This activated of synergies. collaboration, initiated through realise a greater economic impact fromby ( L-R) Dr. Roisinrates Cheshire, Scientific Programme that particular defectiveofviral sequences inin progression should focus on other innovative performance Sigmoid Pharma protective pathways, whichnow in turn prevented a SFI research supplement, highlights the lysine) improves the therapeutic potential of team carried out molecular modelling of the However, of the research in thebasic area to the statemuch investment in oriented A senior postdoctoral researcher, Drof the Coverand of April 2010 edition“Systematic of Biochimica etPatricia Biophysica Manager, Science Foundation Ireland; Dr.evaluation the HIV-1 nef gene or certain regions host viral factors. their application of research and development. the death of the cells that line the potential that innovative indigenous companies date has been based onbusiness observational XT-7 peptide its [G4K]XT-7 in a this naturally occurring peptide. skillsortocase Acta (BBA); Proteins Proteomics. research by teaching McGowan (joint prize& winner); Cian Hughes, Head of McGowan inanalogue the breast cancer protein playworks aand significant role in new disease of large quantities of data by bioinformatics The company has developed two drug gastrointestinal tract,” explained Professor working with academia can realise.” studies rather than rigorous, Operations, Leadership Group university researchers and systematic scientists. research group, led byand Conway Fellow, progression. can be“Our justIrish as Technology importanttrial in refuting technologies, LEDDS™ SmPill™, which not Taylor. pre-clinical data can now scientific evaluation. This by doctoral Taylor’s collaboration with work Sigmoid Pharma has hypotheses thatphase are current in Pharma the literature, as only enhance the solubility and permeability of inform the next Sigmoid product HIV-infected patients can be categorised on candidatebeen Ravindra Pushker set outmetrics to certainly successful by these with it is in discovering unknown patterns”, he said. the drug but can deliver it to targeted locations development pipeline”. the basis of the number of years it takes for determine in a substantially larger sample set three co-authored publications to date in two of in the gastrointestinal tract, including the them to progress to AIDS. Some patients if any association between disease This research wasproduct fundedthat through Sciencein In addition to the is currently the highest rankingexists scientific journals in the colon. maintain stable CD4 lymphocyte counts and progression and particular acid of the Foundation Ireland and University Collegeis phase II clinical studies, Sigmoid Pharma field, Gastroenterology and amino Proceeding do not go on Pharma-Taylor to develop AIDS even after more differences or deletions within the nef gene.

Dublin.

The Sigmoid collaboration is developing a LEDDS™-enabled formulation of National Academy of Sciences, as well as the than 10 years infection. of a new facilitating the of development the generation of proprietary innovative products On a per basis, there was no excess of tracthydroxylase is lined withinhibitor cells that block the contents results in patient both academic outputs and the Irish biopharmaceutical development Missouri, USA at the end of April 2011 Conway Fellow, Dr Patricia Maguire therapeutic approach for the treatment of dimethyloxaloylglycine to bring about and thepatients creation of high-skilled jobs.

Scientists curious as toby why thesescooped longLTNP with onetoward or more defective nef of the gut from leaking (DMOG) into the intestine.

In an application ofwon research clinical product company, are Sigmoid recently where they third place overall and recently hosted aPharma visit Team SAP inflammatory bowel disease (IBD) bygraduate bringing A new fortnightly forum for Conway decided by the members but it is envisaged (thomas.scharzl@ucd.ie )broken and postdoctoral effective, safe and targeted delivery of the this term, non- progressor patients do at not sequences when compared tocompanies.” progressors.

IBD patient, this barrier is and development with indigenous the overall Innovation (LTNP) of the Year award More than 15,000 people in Ireland and the most inspirational team award. together the research methodology oflaunched the Ireland, a group of six transition year and postdoctoral researchers will be that it will include a mix of technology researchers, Dr David Gomez Reference: potential therapeutic agent. develop AIDS. Irish This Times may reflect differences in While the frequency of amino acidwith the contents of the gut leak out into surrounding the inaugural All-Island millions of high people worldwide are living Taylor group school with the proprietary Meta-analysis to test the association HIV-1 Slattery nef amino Commenting onparticular the Taylor collaboration, Dr secondary students andearlytheir in May This initiative will give overviews,IBD informal and formal research (david.gomez@ucd.ie) DrofCraig the host,2010. viral genetics orlife-science environmental replacement at residues is indicative areas.

The research teamand in UCD Conway used Innovation Awards.

The SME, symptoms today.

Current therapeutic acid differences and deletions with disease progression. liquid/emulsion drug delivery system, Coulter said, “The collaboration with the Taylor Team SAP Ireland isrehearsals currentlyand working teacher, Declan Askinbefrom St factors that could potentially exploited for of rapid evolvement, permutation testing a model of IBD and, by applying a new class of founded byMr UCD pharmacology graduate, Dr stage researchers the opportunity to talk about seminars, PhD viva career (craig.slattery@ucd.ie ) invite suggestions for Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields. options forclearly this chronic debilitating disease LEDDS®, developed by Sigmoid Pharma. laboratory demonstrates the potentialare the treatment of the disease. showed that residues with more replacements drugs known as hydroxylase inhibitors, were Ivan Coulter, has actively collaborated with SAP towith develop a within smart phone Journal of Virology, Apr 2010 p3644-3653 Gerard’s College, Castlebar. science and issues that concern them inwith an development talks from and beyond the forum schedule. very limited surgery often being the only that can be realised through focused than expected werecommittee not statistically significant. able to almost completely reverse the Conway Professor Taylor Commenting on the award, Professor Taylor application, iCollapse.

Using the informalinFellow, environment with Cormac refreshments academia.

Forum members, PhD viable option.

The product, currently Studies model organisms have shown that application of basicSigmoid research.

The development symptoms of the disease. since“We being a Science Foundation said, aregranted delighted forofDrstudents Coulter and his in aa phase II Thomas clinical study, uniquely enables accelerometer in the mobile phone, the This exceptional group provided!

Content for the forum will be student Mreconomy Schwarzl infection with nef-deficient virus shows an The researchers conclude that current data of smart will depend on like-minded Ireland industry team and indeed research it reflects partnership well on our award oral delivery a powerful drug without provides no of evidence thatuser’s individual residues attenuated of infection and some “When we applied these new drugs to our IBD collaborative partners identifying opportunities application tracks the movements are gainingcourse national and in 2004. partnership.

A key driver of international successful causing systemic side-effects. model, the gut was tricked into thinking that it and realising basic and applied research and detects a collapse.

This sets off an acclaim for their robotics and scientific research in 2010 is meaningful The Irish Times award recognises the stellar was being deprived of oxygen. This activated synergies.

Thisconditions, collaboration, initiated through Under the gastrointestinal alarmnormal encouraging a passer-by to remove interaction ofengineering academia with industry that in biomedical applications.

(L-R) Team SAP Ireland members Oisin Kyne, Mr Declan innovative performance of Sigmoid Pharma protective pathways, which in turn prevented a SFI research supplement, highlights the Askin (teacher) & Adrian Murphy pictured in Clarity the user’s phone and call the listed help They received aofBritish Science their application research and development. the death of to the cells that line the potential that innovative indigenous companies during a visit UCD. The companyCREST has developed two new drug contact(s). also instructs the passerAssociation award and gastrointestinal tract,” explained Professor working with It academia can realise.” technologies, LEDDS™ and SmPill™, which not Taylor. “Our pre-clinical trial data can now by on how best to help the individual represented Ireland in the First Lego Taylor’s collaboration with Sigmoid Pharma has only enhance the solubility and permeability of inform the next phase Sigmoid Pharma product recover.

League (FLL) World Finals in St Louis, certainly been successful by these metrics with the drug but can deliver it to targeted locations development pipeline”. three co-authored publications to date in two of in the gastrointestinal tract, including the In addition to the product that is currently in the highest ranking scientific journals in the colon. phase II clinical studies, Sigmoid Pharma is field, Gastroenterology and Proceeding of the The Sigmoid Pharma-Taylor collaboration is developing LEDDS™-enabled formulation of National Academy Sciences, well as the Meta-analysis by UCD researchers led by of HIV nef aare critical in determining the rate studies in humansofhave shownas that non facilitating the development of a new the hydroxylase inhibitor Professor Denis generation ofwas proprietary innovative products Conway Fellow, Professor Denis Shields has of disease progression. progression associated with gross Elaine Quinn therapeutic approach for the treatment of dimethyloxaloylglycine (DMOG)for to bring about and the creation of high-skilled jobs. determined that there is no clear evidence Shields believes that searches modifiers of deletions in the nef gene.

Communications & Education Officer inflammatory disease (IBD) by bringing effective, safe and targeted delivery this that particularbowel defective viral sequences in progression rates should now focusofon other More thanmuch 15,000 people in Ireland and However, of the research in the area to together the research methodology of the UCD Conway Institute of therapeutic Biomolecular & Biomedical Research potential agent. the HIV-1 nef gene or certain regions of the host and viral factors.

“Systematic evaluation millions people worldwide are living or with the date hasofbeen based on observational case Taylor the proprietary College Dublin proteingroup play awith significant role in disease of large quantities of University data by bioinformatics symptoms IBD today.

Current therapeutic studies rather than rigorous, systematic liquid/emulsion Belfield, Dublin 4 progression. drug delivery system, can be just as important in refuting options forevaluation. this chronic debilitating disease are scientific This work by doctoral LEDDS®, developed by Sigmoid Pharma. hypotheses that are current in the literature, as Ireland Investing in Your Future very limitedRavindra with surgery often the only HIV-infected patients can be categorised on candidate Pushker setbeing out to it is in discovering unknown patterns”, he said.

Commenting on the award, Professor Taylor viable option.

Sigmoid product, currently the basis of the number of years it takes for determine in aThe substantially larger sample set E: elaine.quinn@ucd.ie said, are delighted for Some Dr Coulter and his in a phase II clinical study, uniquely enables them “We to progress to AIDS. patients if any association exists between disease This research was funded through Science T: (+353-1) 716 6706 team and indeed it reflects well on our oral delivery of a powerful without maintain stable CD4 lymphocyte counts and progression and particulardrug amino acid Foundation Ireland and University College partnership. driver AIDS of successful F: (+353-1) 716 6701 causing systemic side-effects. do not go onAtokey develop even after more differences or deletions within the nef gene.

Dublin. scientific research in 2010 is meaningful W: www.ucd.ie/conway than 10 years of infection.

Under normal conditions, the was gastrointestinal On a per patient basis, there no excess of interaction of academia with industry that Scientists are curious as to why these longLTNP patients with one or more defective nef term, non- progressor (LTNP) patients do not sequences when compared to progressors.

Frog peptide structure selected for journal cover

Pitching Conway to ‘Get collaborator Started’ scoops Irish Times Innovation Award

Bioinformatic analysis of HIV progression studies

collaborator scoops Irish Times Bright ahead for Team Ireland Launchfutures ofConway Conway postdoctoral &SAP graduate forumInnovation Award

Bioinformatic analysis of HIV progression studies

Success in EU FP7 call May 2010 10 september 2007 Issue Summer 2011Issue Issue 141

Conway collaborator scoops Irish Times Innovation Proteomic changes in schizophrenia & bipolar disorder 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 May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3 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 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 flexible analytical tools. Currently, this field Programme. Prospective users can access the 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 Two antibodies thatdevelopment could help block change shape and cause and CJD,the may Reference be Biomolecular and Biomedical and tract is lined with cells that block Science, the contents results intheir bothtool academic outputs Irish biopharmaceutical developed a web-based that interfaces Research by Conway Fellow, Dr Oliver the function of worm Arl13b causes the complex traits including diabetes, GlycoExtractor: A web-based interface forobesity, high genomics and the proteomics. of the gut from leaking into the intestine.

In an application research toward clinical product company, Pharma recently scooped onsetSigmoid of Alzheimer’s disease in the involved inofAlzheimer’s. the UCD Conway Institute who was with the Waters chromatography software throughput processing of HPLC-Glycan data Blacque has revealedofnew informationat ciliary membrane to bulge and become mental retardation andiseven cancer. patient, this barrier broken and the indigenous companies.” theNatalia overall Innovation improve andwith automate the export Researchers, Dr Artemenko andthe Dr Yearinaward brain have been identified a package to development co-corresponding onandthe research.

Natalia V. IBD Artemenko, Matthew P. author Campbell, Pauline about a gene implicated in Joubert of data to various misshapen as well for as affecting the ability M. of Rudd Journal contents of the gutResearch, leak out2010, into surrounding the inaugural Irish Times All-Island of Proteome 9 (4), pp Matthew Campbell from the National Institute file formats subsequent collaborative research project “With an ageing population and increasing Dr Oliver Blacque hopes that these findings Commenting on the Taylor collaboration, Dr 2037–2041 syndrome and related disorders other proteins to properly distribute within areas. The research team in UCD Conway used Innovation Awards.

The cerebellar life-science SME, analysis. The modular architecture of the tool of Bioprocessing Research & Training (NIBRT) Coulter said, “The collaboration with involving scientists at the Medical numbers of families affected by the Taylor useofofIBD these antibodies is of will ultimately leadspecific to applying a greater a“The model and, by a new class founded bycharacterised UCD pharmacology graduate, Drfacilitates byRudd blindness, bone the the ciliary membrane. led by Conway(JSRDs), Fellow, Professor Pauline also manipulation of data from laboratory clearly demonstrates the potential understanding only of JSRDs, butwere also Research Council Prion Unit at other Alzheimer’s disease, there is an urgent need drugs particularly since they have already known exciting as not hydroxylase inhibitors, Ivan Coulter, hascystic actively collaborated with data management have developedabnormalities, an open access, web-based systems. kidneys, that can befound realised through focused They also that a fully functional of closely related ciliopathies such as able to almost completely reverse thetesting Conway Fellow, Professor CormacUCD University College London, for new drugs that can help to preserve undergone extensive pre-clinical for interface that facilitates extraction, querying developmental delay and loss of Taylor muscle application of basic research.

The development The NIBRT Arl13b team are now working to for integrate symptoms of theCJD. disease. since beingInstitute granted a and Science Foundation protein is needed the normal Meckel Gruber and Bardet-Biedl syndrome, and sharing of Conway HPLC-glycan data The generated in Trinity College brain function and prevent memory loss, use in treating So, a lot of basic work tone and control. findings of this of a smart economy will depend on like-minded GlycoExtractor with the EUROCarbDB Ireland industry research partnership award high throughput processes. functioning of awhich protein transport system in as well asapplied perhaps more common has already beenthese done and couldtofast-track Dublin. theprovide symptom most characterises “When we new drugs our IBD identifying opportunities research, to a partners comprehensive highin 2004. funded through a Science framework collaborative cilia.

This intraflagellar transport system models to phenotypes cilium model, the processes gutassociated wasfor tricked into thinking that next it and realising basicpatient and applied research these antibodies usewith in humans. the devastating impact of Alzheimer’s,” identify involved in early The disease (CKD) and improve treatment, Conway researchers led by Dr. Tara throughput HPLC data analysis platform for Glycosylation is the most common and Foundation Ireland President of Ireland The Irish Times award recognises the stellar (IFT) makes contact with from theinitiated ciliary dysfunction such as and was being deprived of mental oxygen.

This activated synergies.

This collaboration, through and investigate novel McMorrow diverse and Professor Michael Ryanand have particular on CKD structurally post-translational the storage andfocus annotation ofarising experimental step is further validation in retardation other disease The antibodies, ICSM-18 ICSM-35, said Professor John Collinge, Director ofCKD progression Young Researcher Award (PIYRA) to with Oliver innovative performance of Sigmoid Pharma in protective in turn amembrane.

SFI research supplement, highlights the onmultiresults,College they strategies obesity. for preventing andwhich slowing the prevented modification proteins.

More than of all data. integration of Based next generation hypertension.

The successfullyof secured €485,500 in half funding models ofpathways, Alzheimer’s and then safety trials were already known to play crucial role Theand the MRC Prion Unit atthese University Blacque, were recently published in diabetes the their application of research andaas development. the death the cellsThese that line the will potential that innovative indigenous companies progression of theofdisease. studies gene products haveaward been shown to bemisfolding; thedisciplinary bioinformatic tools will further thehas proposed a new working model for Arl13b, research consortium 25 part of an overall to has the Systems in humans,” he added. in protein main London, who led the study.

Thepreventing company developed two new drug Journal of Cell Biology.

He notes “That Arl13b associates with ciliary gastrointestinal tract,” explained Professor working with academia can realise.” be integrated with clinical and epidemiological glycosylated.

With many specific glycans or development of unified approaches for partners universities, 9 industry partners) Biology towards Novel Chronic Kidney it functions at the ciliary membrane technologies, LEDDS™ and SmPill™, not (16where cause of Creutzfeldt–Jakob diseasewhich (CJD), Taylor.

“Our pre-clinical trial data can now membranes and is required for cilium across the consortium using systems glycoforms showing potential as cancer handling large scale glycomics data from 15 countries and the project is initiatives duemembrane to run Disease Diagnosis and Treatment (SysKid) One of seven genes associated with JSRDs, to regulate important ciliary Taylor’s collaboration with Sigmoid Pharma studies has only enhance the solubility and permeability of inform the nextto phase Sigmoid Pharma product Clinical trials whether drugs based on the ishuman form ofUnion mad to cow disease.for “We’reinthrilled thatdiscovery this discovery shows in methodologies biology insee order to develop new withfive applications biomarker biomarkers, anEuropean increasing need structure/function in both worms and years. consortium there under the FP7 certainly been successful by these metrics with the drug but can deliver it to targeted locations Arl13b codes for a protein already known to properties such as shape, transmembrane development pipeline”.

NIBRT researchers Dr Matthew Campbell andoptions Dr Natalia diagnostic strategies and treatment to these antibodies can mitigate the damage mice that these two antibodies which we develop high throughput, highly sensitive and mammals demonstrates the remarkable programme. three co-authored publications to date in two of in theroles gastrointestinal tract, including theThe This UCD research wasteam, partially supported by play in the and/or function protein distributions and IFT. Artemenko who development. developed GlycoExtractor Conway including prevent CKD Email robust strategies that detail the formation glycome of caused to to thethe human brain ashow a treatment The study findings published in Nature arehighest developing to scientific treatpostdoctoral CJDjournals may also have evolutionary conservation ofis this small In addition product that currently in the ranking in the colon. of cilia, which hair-like projections researchers Dr. Craig Slattery and Dr. Natalia Syskid (www.SysKid.eu) wasare established to tara.mcmorrow@ucd.ie for details of a PhD phase II clinical studies, Sigmoid Pharma field, Gastroenterology and Proceeding of the for patients with CJD are due to beginisin Communications has shown in mice that a role in treating more common forms of Up to only 20 years ago, many believed G-protein functions.” extending from the surface of the cell.Martin, will National utilise cell cultureofand animalas well as the position developing currently available. further our understanding of chronic kidney The Sigmoid Pharma-Taylor collaboration is a LEDDS™-enabled formulation of Academy Sciences, 2012. these antibodies canmolecular blockof damaging effects dementia likebeAlzheimer’s disease. If these most cilia to redundant cellular facilitating the the precise development a new However, details of Reference the hydroxylase inhibitor generation of proprietary innovative products organelles that have fallen victim to on brain tissue caused by a toxic substance antibody drugs prove to be safe in use to therapeutic approach for the treatment of Joubert syndrome Arl13b functions what exactly Arl13b is doing in cilia have dimethyloxaloylglycine (DMOG) at tociliary bring about and the creation of high-skilled jobs. evolution - a type of cellular called amyloid beta.

Cumulatively, amyloid mammalian treat CJD, we will consider whether studies effective, membranes andand stabilizes protein transport in inflammatory bowel disease (IBD) by bringing safe targeted delivery of this remained unclear.

More than 15,000 people in Ireland and Caenorhabditis elegans.

Cevik S, Hori Y, Kaplan OI, Reference: appendix.

We now know that these cellular together the research methodology of the beta becomes attached to the surface of in Alzheimer’s disease should be carried potential therapeutic agent.

Kida K, Toivenon T, Foley-Fisher C, Cottell D, Katada T, millions ofpresent people worldwide living Taylor group the proprietary Blacque’s team studied the gene inthem the cilia antennae on nearly are all of ourwith cellsthe inwith the brain, stopping from out.”

Commenting research, DrBiol.

Kennedy most likely symptoms to die as aIBD result of the raised New research nerve led bycells Conway Fellow Dr Kontanion K, the Blacque OE. J Cell 2010 Mar 22; today.

Current therapeutic liquid/emulsion drug delivery system, Interaction between prion protein and toxic amyloid of tiny worms (Caenorhabditis elegans) and serve fundamental roles in many May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3 communicating effectively and causing glucose levels seenfor in this diabetes.

Breandán Kennedy indicates that treatment said, “Byβ188(6):953-69 establishing aberobust model for earlyat options chronic debilitating disease are LEDDS®, developed by Sigmoid Pharma. assemblies can therapeutically targeted Glycomics needs the supporting framework cells, tissues and fluids.

EUROCarbDB, a research infrastructure design while collaborators inatthe University of motility andaspect sensory functions, including of diabetic blindness should lookresults memory loss.

The showed that “A unique of this study is that we and late stage diabetic retinopathy, we would very limited with surgery often being the only multiple Freir, Andrew J. Nicoll, of extensive, well-curated databases and study funded bysites. the Darragh EU 6th B. Framework Dr and his team found critical that new Commenting on stopped theparallel award, Professor conducted in Kennedyviable signalling pathways to blood development. protecting the Tokyo neurons responsible for experiments colour Commercial packages that support HPLC hope to Igor better understand the progression of option.

The Sigmoid currently the antibodies amyloidTaylor beta used amyloid beta extracted from human Klyubin, Silvia Panico, Jessica M. Mc Donald, Programme.

Prospective users can access the flexible analytical tools. Currently, thisthe field vessels neuronal cell death inproduct, diabetic said, “We arejust delighted for Dr and his andinthe vision in the eye and not targeting theCoulter cultured human cells.

Together, they instruments cannot facilitate the extraction of the disease andtool pave the way forA.identifying a phase II clinical study,of uniquely enables Emmanuel Risse, Emmanuel Asante, Mark A. from taking hold and damaging brain, the same material we believe is GlycoExtractor on of study lacks proteins the established, retinopathy can arise independently each It is now not surprising that defects in team indeed it reflects well on our blood vessels confirmed as is and currently the practice. large quantities of data.

In an effort to alleviate Farrow, Richard B. Sessions, Helen R. Saibil, Anthony oral delivery of a powerful without new drug targets for its successful treatment”. that Arl13b comprehensive and centralised dataproteins uses lipid In addition, http://glycobase.nibrt.ie:8080/DemoGlycoExtra they identified that cone the brain. causing memory lossfunction in drug patients with this cilium structure and are associated partnership.

A key driver of successful other. this bottleneck within high-throughput R. Clarke, Michael J. Rowan, Dominic M. Walsh & causing side-effects. anchors to associate with the ciliary disease collections, standards and information ctor/mainPage. neurons, those involved inidentified two Nearly 2.5researchers million people worldwide are is blind models to identify processes involved in early (CKD) and systemic improve patient treatment, Conway led by Dr. in Tara devastating disease, and we The research was funded through Science scientific research 2010 meaningfulphotoreceptor with an the everNIBRT expanding glycomic projects, team range have of human John Collinge. Nature Communications Jun 7 2011 reporting protocols that exist within membrane. colour vision and used inCKD daylight, are most due to diabetic retinopathy.

This secondary CKD progression and investigate McMorrow and Professor Michael Ryan have from with particular focus onthat arising from Reference Under normal conditions, the gastrointestinal Foundation Ireland and the Healthnovel Research interaction of academia withfindings industry that The study also confirms a antibodies could block this effect,” doi:10.1038/ncomms1341 developed a web-based tool that interfaces diseases and syndromes, collectively called GlycoExtractor: web-based interface for highthe genomics andof proteomics. affected by high glucoseThe levels. complication diabetes activatesinthe growthas strategies for Apreventing and slowing diabetes andthe hypertension. multisuccessfully secured €485,500 funding Board. with the Waters chromatography software 2009vessels paper by Yale researchers, which first said Professor Dominic Walsh, Professor of throughput processing of HPLC-Glycan Much of thetowork on the project was carried ciliopathies, which have overlapping clinical of new blood inthe the eye and is progression of the disease.

Thesedata studies will disciplinary researchand consortium has 25 part of leaky an overall awardArtemenko Systems Researchers, Dr Natalia and Dr package to improve automate the export V. Artemenko, Matthew P. Campbell, and Pauline Natalia The research team made their observations indicated prion proteins, which Neurodegeneration at the UCD School of UCDthat candidate, Sebihacan features such as polycystic kidneys and be responsible forout theby death ofdoctoral photoreceptors, clinicalResearch, and epidemiological partners (16 universities, 9 industry partners) Biology towards Kidney M. integrated Rudd Journalwith of Proteome 2010, 9 (4), pp Matthew CampbellNovel from Chronic the National Institute of dataa to various file formats for subsequent using novel zebrafish model of diabetes, the neurons that send visual messages to our studies across the consortium using systems Reference: Cevik.

She and her colleagues went on to livers, retinal degeneration, bone 2037–2041 from 15 countries andearly the project isofdiabetic due run Disease Diagnosis and Treatment (SysKid) analysis.

The modular architecture the to tool of Bioprocessing Research & Training (NIBRT) which resembles the stages of brain. methodologies in order to develop Predominant coneatphotoreceptor dysfunction in a new demonstrate in C. elegans how disrupting abnormalities, hydrocephalus, as well as biology Arl13b ciliary membrane for years. consortium under the Professor European Union FP7 led

by Conway Fellow, Pauline Rudd alsofive facilitates the manipulation of data from retinopathy in humans.

It is an exciting diagnostic strategies treatment diabetic options to hyperglycaemic model of and non-proliferative programme. have developed open access, web-based other data management systems. development for the group who now hope to Until now, it wasan unclear if the changes to retinopathy.

Yolanda Alvarez, Jenneth Chen, Alison The UCD Conway team, including postdoctoral prevent CKD development.

Email interfaceand thatneurons facilitates extraction, querying of further extend research and a vessels occurred independently Reynolds, Nore Waghorne, John O’Connor, researchers Dr.their Craig Slattery andestablish Dr. Natalia Syskid (www.SysKid.eu) was established to tara.mcmorrow@ucd.ie for J. details of aBreandan PhD The NIBRT team are now working to integrate and sharing of HPLC-glycan data generated in model of late stage diabetic disease. one other and which type of retinal neuron is Kennedy. Disease Models & Mechanisms (2010) Martin, will utilise cell culture and animal position currently available. further our understanding of chronic kidney GlycoExtractor with EUROCarbDB high throughput processes. by UCD researchers led by Meta-analysis of HIV nef are critical in determining the rate studies inthe humans have shown that non framework to provide a was comprehensive highConway Fellow, Professor Denis Shields has of disease progression. Professor Denis progression associated with gross throughput deletions HPLC data platform for Glycosylation isdetermined the most common that thereand is no clear evidence Shields believes that searches for modifiers of in analysis the nef gene. structurally diverse post-translational the storage and annotation of experimental that defective viral you sequences in progression rates should now focus onMSc otherin larger programmes such as the new We introduced 4ofnew advanced core IIrish amparticular delighted to welcome to thedata. modification ofWelcome! proteins.

More than half of all The integration of next generation However, much the research in the area to tract lined with cells that block the contents results in both academic outputs and the biopharmaceutical development by educating and training highly skilled equipment will be successfully transferred the HIV-1 nef gene or certain regions of the hostisand viral factors.

“Systematic evaluation gene products Conway have been shown to be bioinformatic tools will further the date has been based on observational or case technology modules on a pilot basis this of the gut from leaking into the intestine.

In an application of research toward clinical product company, Sigmoid Pharma recently scooped Focus and look forward to working Imaging commencing in September 2010. protein play a significant role in disease of large of data bysummer bioinformatics staff and conducting ground-breaking into the quantities building over the months. of unified approaches for systematic glycosylated. With many specific glycans studies rather than rigorous, IBD patient, this barrier is in broken and the development with indigenous companies.” the overall Innovation of months! theorYear awarddevelopment at academic year; those covering principles progression. can be just as important refuting with you in the coming research in collaboration withbyindustry.

I am confident that the of With the recent of the National handling large scale glycomics data work initiatives glycoforms showing potential aslaunch cancer scientific evaluation.

This doctoral EUROCarbDB, contents of the gut leak outconsolidation into surrounding the the inaugural Irish Times All-Island Glycomics needs supporting framework cells, tissues and fluids. athat research infrastructure design are current in initiatives, the literature, as and practical aspects of imaging and applied Ihypotheses hope athat number ofinnew Commenting on theto Taylor collaboration, We look forward maintaining this core technology platform will have a Institute for Bioprocessing Research biomarkers, is an increasing need with in biomarker discovery HIV-infected patients canlife-science betocategorised on applications candidate Ravindra Pushker set out close to Drlinks areas.

The research team UCD Conway used Innovation Awards.

The SME, study funded by the EU 6th Framework of extensive,there well-curated databases and it is in discovering unknown patterns”, he said. proteomics began in lateHPLC March and run researchers Coulter said, “The collaboration with thewill Taylor packages support NIBRT Dr Matthew Campbell and DraNatalia As institute with anthis increasingly including the researcher forum develop high throughput, highly sensitive andfarewell the an basis of Currently, the number of years it takesCommercial for determine inthat aand substantially larger sample set apositive model ofimpact IBDearly-stage and, by applying newthe class of founded by UCD pharmacology graduate, Dr with Pauline rest of the NIBRT team on service delivery for our and Training (NIBRT), we bid to flexible analytical tools. field Programme.

Prospective users can access This research was partially supported by two laboratory clearlywith demonstrates the Artemenko who developed GlycoExtractor instruments facilitate thea extraction ofpotential until mid-June further modules in robust the research glycome of herpatients them todetail progress to AIDS.and Some ifcannot any association exists between disease This research was fundedwill through Science drugs known as hydroxylase inhibitors, were Ivan Coulter, has actively collaborated with interdisciplinary focus and GlycoExtractor toolinon of studystrategies lacks Professor thethat established, described this issue, not only through the many research collaborations researchers.

Pauline Rudd teamlarge as quantities that can be realised through focused of data.

In an effort to alleviate maintain stable CD4 lymphocyte counts and progressionand andflow particular aminotaking acid place Foundation Ireland and University College genomics cytometry able to almost completely reverse the Conway Fellow, Professor Cormac Taylor comprehensive and centralised data http://glycobase.nibrt.ie:8080/DemoGlycoExtra expertise in specialist technology platforms, strengthen the community of Conway they Institute building for their established other Conway Fellows. application of basic research.

The development this bottleneck within high-throughput do notleave goand onthe to develop AIDS even after more differences orwith deletions within thethe nef gene.ctor/mainPage.

Dublin. of the disease. symptoms since being granted a Science Foundation collections, standards information over week-long periods during summer of a smart economy will depend on like-minded new home across campus.

Minister for Professor Walter Kolch glycomic projects, the NIBRT team have we are uniquely placed to participate in the researchers and forge new interdisciplinary than 10 years of within infection. partnership award Ireland industry research reporting protocols that exist Reference months.

On aco-localisation per patient there was opportunities no excess of “When we applied these new drugs to our IBD partners identifying developed acollaborative web-based toolbasis, thatof interfaces Innovation, Sherlock The all imaging facilities Director in 2004. & education and training ofSeán the next links Abut will celebrate heighten GlycoExtractor: web-based interface and for high genomics and Research proteomics.

Scientists are curious as to why these longLTNP patients with one or more defective nef model, the gut was tricked into thinking that it and realising basic and applied research with the Waters chromatography software throughput processing of HPLC-Glycan data TD officially opened the new 6,500sq to the lower ground floor of the Institute is The Irish Times award recognises the stellar generation of research scientists.

The newly awareness of our research and innovation term, nonprogressor (LTNP) patients do not sequences when compared to progressors. was being deprived of oxygen.

This activated synergies.

This collaboration, initiated through Researchers, Dr Natalia Artemenko and Dr package to We improve automate from the export hope and to determine this pilot if Natalia V. Artemenko, Matthew P. Campbell, and Pauline Reference: innovative performance of Sigmoid Pharmainin metre facility that willInstitute support the now the final stage of completion. develop AIDS. This may reflect differences While the high frequency ofhighlights amino acid M. Rudd Journal of Proteome Research, 9 (4), pp protective pathways, which 2010, in turn prevented ademand SFI entering research supplement, theas well launched PhD programme in Bioinformatics Matthew Campbell from the National of data to various filefor formats for subsequent successes. training from within UCD Meta-analysis to test the association of HIV-1 nef amino their application of research andindevelopment.

2037–2041 industry Irelandanalysis.

We anticipate that all indigenous electron microscopy the host, viral&genetics orDr environmental replacement at particular residues iscompanies indicative the death of the cells that line the progression. potential innovative Commenting on the research, Drwith Kennedy most likely to die asthat a result of the raised New research biopharmaceutical ledResearch by Conway Fellow of Bioprocessing Training (NIBRT) The modular architecture of the tool acid differences and deletions disease and Systems Biology recently attracted 80 as from external academic centres and The company has developed two new drug factors that could potentially be exploited for of rapid evolvement, permutation testing gastrointestinal explained Professor working with academiaofcan realise.” glucose levels seen in diabetes.

Breandán Kennedy indicates thatPauline treatment said, “By establishing robust model for early led

by Conway Fellow, Professor Rudd also facilitates the manipulation data from Ravindra Pushker,atract,” Jean-Marc Jacquē, Denis C. Shields.

Professor Walter Kolch EU and 120 non-EU applicants for up to 15 technologies, LEDDS™ and SmPill™, which not industry will residues dictate stand-alone delivery of the of look theweb-based disease. showed that with more replacements Journal of Virology, Apr 2010trial p3644-3653 pre-clinical data can now of diabetic blindness should at have developed antreatment open access, other data management systems. and lateTaylor. stage “Our diabetic retinopathy, we would Taylor’s collaboration with Sigmoid Pharma has Dr Kennedy and his team found that new blood only enhance the solubility and permeability of than expected were not statistically significant. these advanced modules or inclusion within Director, UCD Institute studentships. next Conway phase Pharma protectingthat thefacilitates neurons extraction, responsiblequerying for colour interface hope to inform better the understand theSigmoid progression of product Studies inbut model organisms have shown thatNIBRT these metrics with vessels andcertainly the neuronal cell deathtoby inintegrate diabetic the drugnot can targeting deliver it tothe targeted locations The team arebeen nowsuccessful working development pipeline”. vision in theofeye and just and sharing HPLC-glycan data generated inshows an infection with nef-deficient virus The researchers conclude thateach current data three co-authored publications to date in twothe of disease and pave the way for identifying retinopathy can arise independently of in the gastrointestinal tract, including the GlycoExtractor with the EUROCarbDB bloodthroughput vessels asprocesses. is currently the practice. high its successful provides noaranking evidence that attenuated course of infection and someframework In targets additionfor to the product thattreatment”. is currently in the highest scientific journals in the new drug other. In addition, they identified thatindividual cone colon. to provide comprehensive high- residues phase was II clinical studies, Sigmoid Pharma is field, Gastroenterology and Proceeding of the photoreceptor neurons, those involved infor Nearly 2.5 million people are blind Glycosylation is the most worldwide common and throughput HPLC data analysis platform The research funded through Science The Sigmoid Pharma-Taylor collaborationcolour is developing aand LEDDS™-enabled formulation of National Academy Sciences, as well as theFoundation vision andannotation used in daylight, are most due to diabetic retinopathy.

This secondary structurally diverse post-translational the storage and ofofexperimental Ireland the Health Research development of a new the hydroxylase inhibitor generation of next proprietary affected the high glucose levels. innovative products complication of offacilitating diabetes the activates growth modification proteins.

More thanthe half of all data.

Thebyintegration of generation

Conway collaborator scoops Irish Alzheimer’s Times Award Wormavenue research geneInnovation function New toreveals tacklecilia CJDdisease and disease

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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Conwayalternate collaborator scoopsofIrish Innovation Award c-Myc impacts splicing keyTimes signalling factors

Conway collaborator scoops Irish Times Innovation Award Conway collaborator scoopsmove Irish Times New prostate cancer biomarkers closerInnovation to clinicalAward use Irish biopharmaceutical development

company, Sigmoid Professor Pharma recently scooped Conway Fellow, William Irish biopharmaceutical development the overalland Innovation of the Year award at company, Sigmoid Pharma recently scooped Watson Professor John Fitzpatrick, the Irish Times All-Island the inaugural overall Innovation of the Year Medical award at UCD School of Medicine and Innovation Awards.

The life-science the inaugural Irish Times All-Island SME, Science and Mater Misericordiae founded

by Awards.

UCD pharmacology graduate, Innovation Therecently life-science SME,Dr University Hospital received Ivan Coulter, haspharmacology actively collaborated founded by UCD graduate, Dr a translational research award forwith Conway Fellow, Cormac Taylor Ivan Coulter, hasProfessor actively collaborated the validation of a panel of serum with Conway Fellow, Professor Cormac Taylor since being granted a Science Foundation biomarkers to inform surgical since being granted a Science Foundation Ireland industry research partnership award intervention for prostate cancer.

Ireland in 2004.industry research partnership award

in 2004.

The Times award recognises OneIrish of four research projects tothebestellar The Irishunder Times award recognises the stellarin innovative performance ofHealth SigmoidResearch Pharma funded the joint innovative of Sigmoid Pharma in their application of research and development.

Board andperformance Science Foundation Ireland theircompany application ofdeveloped research and The twodevelopment. new drug initiative, thishas proposal ultimately The company has developed two new which drug not aims to develop a clinically-applicable technologies, LEDDS™ and SmPill™, technologies, LEDDS™ and SmPill™, which predictive tool identifyand thepermeability grade andnot only enhance theto solubility of only enhance the solubility and permeability of stage of prostate cancer and inform the drug but can deliver it to targeted locations the drug but can deliver it tooftargeted locations the patient the most in theclinician gastrointestinal tract, including the May 2010.qxd:Layout 1and copy 07/05/2010 in the gastrointestinal tract, including the 13:12 appropriate treatment strategy. colon. colon.

The collaboration is is The proposalPharma-Taylor is based on recently The Sigmoid Sigmoid Pharma-Taylor collaboration facilitating ofdata newby the published anddevelopment preliminaryof facilitating the the development aa new UCD prostate cancer and willof therapeutic approach forgroup the treatment treatment of therapeutic approach for the involve independent external inflammatory bowel disease (IBD)validation by bringing bringing inflammatory bowel disease (IBD) by of the panel of proteins by international together the methodology of the the together the research research methodology of collaborators in Austria and Australia Taylor group with the proprietary prior to any commercial development liquid/emulsion drug delivery system, taking place.

LEDDS®, developed by Sigmoid Pharma.

Professorstudent) Taylor Commenting the award, Dr Sheng-FeionOon (MD research for Dr Coulter and his published reviews in Nature Reviews said, “We are delighted team and and indeed reflects well on our Urology theit BJU International partnership.

A key key driver driver of that systematically identified, for the partnership.

A of successful successful scientific research research in in 2010 scientific 2010 is is meaningful meaningful interaction of of academia academia with interaction with industry industry that that

results in both academic outputs and the

application of research toward clinical product first time, all the areas of greatest results in both academic outputs and the development indigenous unmet need for biomarkers in prostate application of with research towardcompanies.” clinical product cancer and has directed thecompanies.” focus of Dr development indigenous Commenting with on the Taylor collaboration, international biomarker research efforts Coulter said, “The collaboration with the Taylor Commenting on maximising the Taylor collaboration, Dr to these areas clinical utility. laboratory clearly the potential Coulter said, “The demonstrates collaboration with the Taylor

that can beclearly through focused laboratory demonstrates potential Taking thisrealised as a guide, Mr Yuethe Fan (PhD application basic research.

The development that can be realised through focused student onof the UCD Bioinformatics application of basic research.

Theon development of a Systems smart economy willPhD depend like-minded and Biology programme) of a smart economy depend and on like-minded collaborative partnerswill identifying opportunities used a proteomics approach novel collaborative opportunities and realising partners basic andidentifying applied research bioinformatics analysis to identify lists of and realising basic andprotein appliedinitiated researchthrough synergies.

This collaboration, potential candidate biomarkers. synergies.

Thissupplement, collaboration, through a SFI research the These findings, publishedhighlights ininitiated the Journal apotential SFI research supplement, highlights the of Proteome Research, will help stratify that innovative indigenous companies potential that innovative indigenous companies prostate cancer patients into their working with academia can realise.” working with treatment academia can realise.” appropriate groups.

Taylor’s collaboration with Sigmoid Pharma has Taylor’s collaboration with Sigmoid Pharma has

certainly been successful by these metrics with “There many hundreds of biomarkers certainlyare been successful by these metrics with three co-authored publications to date in two of for prostate cancer but only one inin Page 3 three co-authored publications to date two of the highest ranking scientific journals in the clinical useranking because the others have the highest scientific journals in the field, Gastroenterology Gastroenterology and Proceeding of the the either not succeededand in the validation field, Proceeding of National Academy ofdeemed Sciences,useful as well wellatas as the the phase orAcademy were notof National Sciences, as the bedside” stated Professor William generation of proprietary proprietary innovative products generation of innovative products Watson who leads the groupjobs. and and the the creation creation of high-skilled high-skilled jobs. and of the Irish Prostate Cancer Research More than than 15,000 15,000 people in Ireland Ireland and Consortium.

“Wepeople have in taken theand More millions of of of people worldwide are living living with the the approach firstly identifying the with millions people worldwide are symptomsclinical IBD today.

Currentand therapeutic relevant questions then therapeutic designing discovery disease and are debilitating disease are options for appropriate this chronic debilitating validation with aoften clearly defined very limitedefforts with surgery being the often being the only only comparison carefully viable option. population The Sigmoidusing product, currently product, currently calibrated standardised collection, in a phase IIand clinical study, uniquely enables uniquely enables storage andofprocessing oral delivery a powerful protocols.” drug drug without without causing causing systemic systemic side-effects. side-effects.

tract is lined with cells that block the contents of theismulti-faceted, gut from intounified the intestine.

In an This tract lined withleaking cells but that block theapproach contents IBD patient, thisleaking barrierinto is broken and theIn an is the placing Irish-based prostate cancer of gut from the intestine. contents ofinthe leakisout intomany surrounding research thegut forefront of IBD patient, this barrier broken and the areas.

The team in into UCDsurrounding Conway international prostate cancer researchused contents of research the gut leak out ainterests. model ofresearch IBD and,team by applying new class areas.

The in UCD aConway usedof hydroxylase inhibitors, wereof adrugs modelknown of: IBDasand, by applying a new class Reference Fan Y,toMurphy TB, Byrne JC, Brennan L, Fitzpatrick able almost reverse the were drugs known ascompletely hydroxylase inhibitors, JM, Watson RW. Applying random forests to identify able to almost completely reverse the symptoms of the disease. biomarker panels serum 2D-DIGE data for the symptoms of thein disease. detectionwe and stagingthese of prostate Proteome “When applied newcancer. drugs Jto our IBD Res. 2011 Mar 4;10(3):1361-73.

“When we applied newinto drugs to ourthat IBDit model, the gut wasthese tricked thinking model, the deprived gut was tricked into This thinking that it was being of oxygen. activated Oon being SF, Pennington SR,ofFitzpatrick JM, Watson RW. was deprived oxygen.

This activated protective pathways, which in turn prevented Biomarker research in prostate cancer-towards protective pathways, which in turn prevented the death of the Nat cellsRev that line theMar;8(3):131utility, not futility.

Urol.

2011 the death of the tract,” cells that line theProfessor gastrointestinal explained 8. gastrointestinal tract,” explained Taylor. “Our pre-clinical trial dataProfessor can now Taylor. pre-clinical trial data canJM. now Oon SF,“Our Watson RW, O’Leary JJ, Fitzpatrick Epstein inform the next phase Sigmoid Pharma product inform the next phase Sigmoid Pharma product Criteria for prostate cancer. BJU Int. 2011 Feb 14. doi: development pipeline”. development pipeline”.

10.1111/j.1464-410X.2011.09979.x.

[Epub ahead of print] In addition to the product that is currently in In addition to the product that is currently in phase clinical studies, studies, Sigmoid Sigmoid Pharma Pharma isis phase IIII clinical developing aa LEDDS™-enabled LEDDS™-enabled formulation formulation of of developing the hydroxylase hydroxylase inhibitor inhibitor the dimethyloxaloylglycine (DMOG) (DMOG) to to bring bring about about dimethyloxaloylglycine effective, safe safe and and targeted targeted delivery delivery of of this this effective, potential therapeutic therapeutic agent. agent. potential

Pictured at the HRB-SFI Translational Research Award announcement (L-R); Minister for Research and Innovation, Mr Sean Sherlock T.D; Professor William Watson; Minister for Health, Dr James Reilly T.D.

Conway collaborator scoopsinflammation Irish Times Innovation Award Protecting against adipose tissue in obesity Obesity is a growing pandemic Irish biopharmaceutical development that imposes substantial healthscooped & company, Sigmoid Pharma recently economic burdens globally. the overall Innovation of the YearLeading award at to complications such themetabolic inaugural Irish Times All-Island as insulin Awards. resistance type II SME, Innovation The and life-science diabetes, has significant founded byobesity UCD pharmacology graduate, Dr Meta-analysis by UCD researchers led by ramifications for patients, families and Ivan Coulter, has actively collaborated with Meta-analysis by UCD researchers led by Conway Fellow, Fellow, Professor Professor Cormac Denis Shields communities.

Conway Taylor has

Under Under normal normal conditions, conditions, the the gastrointestinal gastrointestinal

further locally with and secretion results inenhanced both academic outputs the of pro-inflammatory cytokines from the application of research toward clinical product expanding tissue mass itself. developmentadipose with indigenous companies.”

This leads to both adipocyte specific and Commenting on the Taylor collaboration, Dr systemic insulin resistance.

tract is lined with cells that the contents equivalent immune cell block recruitment. of the gut from leaking into the intestine. In an IBD patient,be this is broken and the ‘It would anbarrier over-simplification of contents of thetogut outIL-1 intohas surrounding the process sayleak that a direct areas. research team in UCD of Conway used linearThe effect on the majority adipose atissue modelinflammation,’ of IBD and, by applying a new class of said Professor of HIVknown nef areascritical in determining thewere rate drugs hydroxylase inhibitors, Helen ‘We surmise that crosstalk of disease HIV Roche. nef progression. are critical in Professor determining the rate of Denis able to almost completely reverse the between adipose derived cytokines is the of disease progression.

Professor Denis of Shields believes searches foradipose modifiers symptoms of scenario the that disease. most likely whereby Shields believes searches for modifiers progression ratesthat should now focus on otherof tissue inflammation is amplified. progression rates should now focus on “When we viral applied these new drugs to ourother IBD host and factors.

“Systematic evaluation model, the gut was tricked intobioinformatics thinking that it host and viral factors.

“Systematic evaluation of large quantities of data by However, the contribution of IL-1 was being deprived oxygen.

This activated ofcritical large quantities of data bioinformatics can be just important inby refuting is toasthe medley of proprotective pathways, can be just as ininrefuting hypotheses thatimportant are which current inturn the prevented literature, as inflammatory, insulin-desensitising the of the that linein the ithypotheses isdeath in discovering patterns”, he said. thatcells are current the literature, as signals relevant tounknown obesity-induced gastrointestinal tract,” Professor it is in discovering unknown patterns”, he said. insulin resistance.

Asexplained such, these findings This research was funded through Science Taylor.

“Our trial data can now expand ourpre-clinical current understanding of the Foundation Ireland and University College This research was funded through Science inform the next phase Sigmoid Pharma paracrine effect associated with theproduct lack Dublin.

Foundation Ireland and University College development of IL-1R1 in pipeline”. adipose tissue’.

Dublin.

In addition to the product that is currently in phase II clinical studies, Sigmoid Pharma is Reference : a LEDDS™-enabled formulation of developing Reference: Lack of Interleukin-1 Receptor I (IL-1RI) Protects Mice the hydroxylase inhibitor Meta-analysis test the association of HIV-1 nef amino From High-FattoDiet–Induced Adiposeto Tissue about Reference: dimethyloxaloylglycine (DMOG) acid differences and deletions with diseasebring progression.

Inflammation Coincident With Improved Glucose Meta-analysis test the association ofDenis HIV-1 nef amino Ravindra Pushker, Jean-Marc Jacquē, Shields. effective, safetoand targeted delivery ofC.this Homeostasis.

Fiona C. McGillicuddy,Karen A. acid differences and deletions with disease progression.

Journal of Virology, Apr 2010 p3644-3653 potential therapeutic agent.

Harford, Clare M. Reynolds, Elizabeth Oliver, Mandy

Bioinformatic analysis Bioinformatic analysis of of HIV HIV progression progression studies studies

Conway Fellow, Professor Shields has determined there is noDenis clear evidence since being that granted a Science Foundation determined that there is no clear evidence that particular defective viral sequences in Even our bodiesresearch recognise the threat Ireland industry partnership award that particular defective viral sequences in the2004.

HIV-1 nefobesity gene or as certain imposed by theyregions mount of the in HIV-1 nefagene or certain regions of the protein play significant role in disease athe pathological immune response to The Irishplay Times award recognises the stellar protein a significant role in disease progression. the condition.

Scientists believe that in innovative performance of Sigmoid Pharma progression. interrogating the biochemical pathways their application of research development.

HIV-infected patients can be and categorised on underlying this immune response may The company has developed two itnew drug the basis of the number takes for HIV-infected patients canofbeyears categorised on give insight into therapeutic options. technologies, LEDDS™ and SmPill™, which them to progress to AIDS. the basis of the number of Some years itpatients takes for not only enhance theCD4 solubility and permeability maintain stable lymphocyte counts and of them to progress to AIDS. Some patients UCD researchers led by Conway Fellow, the drug deliver itAIDS to targeted locations do not gobut oncan to CD4 develop even after more maintain stable lymphocyte counts and Professor Helen Roche are contributing in the gastrointestinal tract, including the more than 10 years of infection. do this not go on toand develop AIDS even after to effort their recent findings colon. than 10 years of infection. have been published Scientists are curious asintothe whyhighest these longimpact journal in this(LTNP) scientific field, The Sigmoid Pharma-Taylor collaboration term, nonprogressor patients do is not Scientists are curious as to why these longDiabetes. facilitating the development of adifferences new develop AIDS. This may reflect in term, non- progressor (LTNP) patients do not therapeutic approach treatment of the host, viral geneticsfororthe environmental develop AIDS. This may reflect differences in In obesity, of the immune system inflammatory bowel disease (IBD) by bringing factors that cells could potentially be exploited for the host, viral genetics or environmental (macrophages respondofto together the research methodology thea the treatment of & theT-cells) disease. factors that could potentially be exploited high fat diet by entering adipose tissuefor Taylor group with the proprietary Studies in model organisms shown that the treatment ofproinflammatory the disease. and releasing cytokines liquid/emulsion drug deliveryhave system, infection with nef-deficient viruscreates shows an (Studies IL-1, IL-6, TNF-alpha).

This a LEDDS®, developed by Sigmoid Pharma. in model organisms attenuated course of infectionhave andshown someis that chronic state of inflammation that infection withon nef-deficient showsTaylor an Commenting the award, virus Professor attenuated course of infection and some said, “We are delighted for Dr Coulter and his team and indeed it reflects well on our partnership. A key driver of successful scientific research in 2010 is meaningful

Coulter said, “The collaboration with the Taylor

laboratory demonstrates the potential studies in clearly humans have shown that non The Science Foundation Ireland studies humans have shown that non can in beRoche realised through focused progression was associated with gross –that funded group have shown that progression was associated with application basic research.

The gross development deletions inofthe nef gene. inflammatory signals transmitted via the deletions the nefcytokine, gene. of a smart in economy will depend on like-minded proinflammatory interleukin-1 However, much of theidentifying research inopportunities the area to collaborative partners receptor (IL-1R1) play a key role in area adipose However, much of and theonresearch in the to date has been based observational or case and realising basic applied research tissue inflammation during obesity. date hasrather been than basedrigorous, on observational studies systematicor case synergies. This collaboration, initiated through studies rather than rigorous, systematic scientific evaluation.

This work by doctoral

a SFImust research supplement,tohighlights the IL-1 be converted anby active candidate Ravindra Pushker set out to scientificthat evaluation.

This work doctoral potential innovative indigenous companies form by NLRP3-capase-1 inflammasome determine in academia a substantially larger set candidate Ravindra Pushker set outsample to working with can realise.” complex.

The active form of IL-1 then ifdetermine any association exists between disease in a substantially larger sample binds downstream to itsSigmoid receptor IL-1R1set in Taylor’s collaboration with Pharma has progression and particular amino disease acid if any to association exists between order control the inflammatory signals certainly been successful byamino these metrics with differences orand deletions within the acid nef gene. progression particular that mediate adipose inflammation intwo of three co-authored publications to in differences or deletions within thedate gene. obesity.

On a per patient basis, there was nonef excess the highest ranking scientific journals in the of LTNP patients with oneand or more nefof field, Proceeding of the On a Gastroenterology per patient basis, there wasdefective no excess

The UCD team focused sequences when compared todownstream progressors.

National Academy ofone Sciences, asdefective well as the LTNP patients with oron more nef consequences ofcompared IL-1RI innovative receptor signalling While the high frequency of amino acid generation proprietary products sequencesof when to progressors. in this pathway murine models. replacement at particular residues is indicative and thethe creation ofusing high-skilled jobs.

While high frequency of amino acid They evaluated macrophage of rapid evolvement, permutationrecruitment, testing replacement at particular residues isand indicative More than 15,000 people Ireland cytokine secretions and insulin showed that residues withinadipocyte more replacements of rapid evolvement, permutation testing millions of people worldwide are living sensitivity.

They found that a lack ofwith IL- the than expected were not statistically significant. showed that residues with more replacements 1RI protects against high fattherapeutic diet induced symptoms IBD today. Current The conclude that current data are thanresearchers expected not debilitating statistically significant. insulin resistance and reduces local options for thiswere chronic disease provides no with evidence thatoften individual residues adipose tissue inflammation despite very limited surgery being the the only The researchers conclude that current data viable option. The Sigmoid product, currently provides no evidence that individual residues in a phase II clinical study, uniquely enables oral delivery of a powerful drug without causing systemic side-effects.

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

Claessens, H.G.2010 Millsp3644-3653 and Helen M. Roche.

Journal of Kingston Virology, Apr Diabetes doi:10.2337/db10-1278 June 2011.

New research shows that the protocontrols expression of the results in the bothgenetic academic outputs and the Irish biopharmaceutical development oncogenic factor,Pharma c-Myc recently directlyscooped affects splice factor, hnRNP H. Expression application of research toward clinical of product company, Sigmoid the alternate splicing of at hnRNP H is necessary to ensure that a-raf the overall Innovation of machinery the Year award development with indigenous companies.” key signalling components in an effort mRNA is spliced in such a way as to form a the inaugural Irish Times All-Island Commenting on theprotein.

Taylor collaboration, to coordinate cellThe processes suchSME, as full length A-Raf This protein Dr can Innovation Awards. life-science Coulter said, “The collaboration with to theMST2 Taylor growth, proliferation, differentiation then inhibit apoptosis by binding founded by UCD pharmacology graduate, Dr laboratory clearly demonstrates potential and findings of the with kinase, which is seen typicallythe in human Ivan apoptosis.

Coulter, hasThe actively collaborated that can be head realised focused international ledTaylor by colon and andthrough neck cancers.

Conway Fellow,collaboration Professor Cormac disease (CKD) and improve treatment, Conway researchersKolch, led by Director, Dr. Tara application of basic research.patient The development Professor since beingWalter granted a Science Foundation of a smart economy will depend on like-minded McMorrow and Professor Michael Ryan have with particular focus on CKD arising from Systems Biology Ireland & UCD Conway They also describe a novel splice product disease (CKD) and improve patient treatment, Conway researchers led by Dr. Tara Ireland industry research partnership award May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3 partners collaborative opportunities Institute were published recently inhave the diabetes and hypertension. multior truncated protein called A-Raf successfully secured €485,500 inRyan funding as McMorrow Professor Michael with particular focus onidentifying CKDThe arising from that in 2004. and SHORT and realising basic andconsortium applied research journal, Research. occurs when low levels ofThe c-Myc result disciplinary has 25 part of anCancer overall award to the Systems diabetes and research hypertension. multisuccessfully secured funding The Irish Times award€485,500 recognisesinthe stellaras synergies.

This collaboration, initiated through in reduced expression of the hnRNPH partners (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney disciplinary research consortium has 25 part of an overall awardoftoSigmoid the Systems innovative performance Pharma in a SFI research highlights the It Occurring in more than ninety percent splice factor insupplement, normal cells and istissues. from 15 countries and the project due to run Disease Diagnosis and Treatment (SysKid) partners (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney their application of research and development. potential that that innovative indigenous companies of genes,Diagnosis alternate splicing is aUnion way of appears A-Raf acts like tumour SHORT for five from 15 years. countries and the project is adue to run consortium under the FP7 Disease andEuropean Treatment (SysKid) The company has developed two new drug working withprotein academia realise.” against regulating protein expression Union and activity. suppressor bycan safeguarding for five years. consortium under the European FP7 programme. technologies, LEDDS™ and SmPill™, It describes how a common strandwhich of not oncogenic transformation.

The UCDcollaboration Conway team, Taylor’s withincluding Sigmoidpostdoctoral Pharma has programme. only enhance the solubility and permeability of genetic information is cut orestablished spliced toto The UCD been Conway team,Slattery including researchers Dr.successful Craig andpostdoctoral Dr. Natalia Syskid (www.SysKid.eu) was certainly by these metrics with the drug but can deliver it to targeted locations produce different mature RNA strands.

As A-Raf fails to bind MST2 kinase, it researchers Dr. Craig Slattery and Dr. Natalia Syskid (www.SysKid.eu) was established to SHORT Martin, will utilise cell culture and animal further our understanding ofincluding chronic kidney three co-authored publications to date in two of in the gastrointestinal tract, the These splice products oroftruncated proteins Martin, cannot regulate MST2 mediated apoptosis. will utilise culture and animal further our understanding chronic kidney the highest rankingcell scientific journals in the colon. introduce diversity into cells even to the However, it does bind and block activated field, Gastroenterology and Proceeding of the extent of producing antagonistic functions.

Ras and consequently suppresses the RasThe Sigmoid Pharma-Taylor collaboration is National Academy of Sciences, as well as the ERK signalling pathway that is commonly facilitating the development of a new generation of proprietary innovative products The research team report activated in cancer. therapeutic approach for the that treatment of and the creation of high-skilled jobs. protooncogenic factor, c-Myc inflammatory bowel disease (IBD)directly by bringing

Success in EU FP7 call Success in EU FP7 call

‘These results that a concerted tract is lined withsuggest cells that block the contents response of c-Myc, hnRNP and A-Raf of the gut from leaking into theHintestine.

In an expression is part of aisphysiological IBD patient, this barrier broken and the programme defining cellssurrounding respond contents of the gut leakhow out into to different growthteam conditions.

We were areas.

The research in UCD Conway used ableofto demonstrate thatac-Myc is of aalso model IBD and, by applying new class coordinating response,’inhibitors, said Professor drugs known asthis hydroxylase were Walter Kolch.completely reverse the able to almost models to identify processes involved in early symptoms of the disease.

CKD progression and novel Cancer UK investigate and Science models toResearch identify processes involved in early “When we applied these new to research our strategies forIreland preventing anddrugs slowing the IBD Foundation supported this CKD progression and investigate novel model, thefor gutof was thinking thatwill it progression the tricked disease.

These studies that also involved researchers from strategies preventing andinto slowing thethe was beingInstitute deprived of oxygen.

This activated be integrated clinical and epidemiological Beatson for Cancer Research, progression of with the disease.

These studies will protective pathways, which in epidemiological turn prevented Glasgow; University of Sheffield, UK; studies across theclinical consortium using systems be integrated with and the death of thethe cells the Garvan Institute of that Medical Research, biology methodologies inline order to develop studies across consortium using systemsnew gastrointestinal tract,”and explained Australia; Ludwig-Maximilians University, diagnostic strategies treatment options to biology methodologies in order toProfessor develop new Taylor. pre-clinical data can now to Germany. diagnostic strategies andtrial treatment options prevent“Our CKD development.

Email inform the phase Sigmoid Pharma prevent CKDnext development. tara.mcmorrow@ucd.ie forEmail details of a product PhD development pipeline”. for details of a PhD tara.mcmorrow@ucd.ie Reference position currently available. c-Myc regulates splicing ofthat the A-Raf kinase andinits position currently available.

In addition to RNA the product is currently activation of the ERK pathway. Jens Rauch, Kim Moran-

phase II clinical studies, Sigmoid Pharma is Jones, Valerie Albrecht, Thomas Schwarzl, Keith Hunter, developing LEDDS™-enabled formulation Olivier Gires &aWalter Kolch. Cancer Res( E-Pub) Aprilof 21, the inhibitor 2011.hydroxylase doi:10.1158/0008-5472 dimethyloxaloylglycine (DMOG) to bring about effective, safe and targeted delivery of this potential therapeutic agent.

EUROCarbDB, a research infrastructure design EUROCarbDB, a research infrastructure design study funded by the EU 6th Framework study funded by the EU 6th Framework Programme. Prospective users can access the Programme. Prospective users can access the GlycoExtractortool toolon on GlycoExtractor tract is lined with cells that block the contents This collaborative research project also http://glycobase.nibrt.ie:8080/DemoGlycoExtra http://glycobase.nibrt.ie:8080/DemoGlycoExtra of the gut Dr from leaking into theTrinity intestine.

In an involved Neil Docherty, College ctor/mainPage. ctor/mainPage.

IBD patient, this barrier is broken and the

GlycoExtractor advances advances glycan glycan data data manipulation manipulation GlycoExtractor

More than 15,000 people in Ireland and together the research methodology of the cells, tissues and fluids.

Glycomics needs the proprietary supporting framework millions of people worldwide are living with the Taylor group withthe the cells, tissues and fluids.

Glycomics needs supporting framework of extensive, well-curated databases and symptoms IBD today. Current therapeutic liquid/emulsion drug delivery system, and of extensive, well-curated databases Commercial packages that support HPLC flexible analytical tools.

Currently, this field Commercial packages support HPLC options for this chronicthat debilitating disease are LEDDS®, developed

by Sigmoid Pharma. flexible analytical tools.

Currently, this field instruments cannotfacilitate facilitate the extraction instruments the extraction ofof very limited cannot with surgery often being the only of study lacks the established, of study lacks the established, large quantities of data.

In an effort tothe alleviate results in bothThe academic outputs and Irish biopharmaceutical Commenting on and the award, Professor Taylor While inflammation isdevelopment an integral of converging processes involving large quantities of data.

In an effort to alleviate viable option.

Sigmoid product, currently comprehensive centralised data comprehensive and Pharma centralised data scooped this bottleneck within high-throughput application research toward clinical product company, Sigmoid recently said, “We are delighted for Dr Coulter and his part of the body’s natural immune macrophage activation and the clearance this within high-throughput in a bottleneck phase IIofclinical study, uniquely enables collections, standards and information collections, standards and information development with indigenous companies.” the overall Innovation of the Year award team and indeed it reflects well on our glycomic projects, theNIBRT NIBRT team have response,protocols it can become part of a at of dead cells or efferocytosis. glycomic projects, the team have oral delivery of a powerful drug without reporting that exist within reporting protocols that exist within the inaugural Times partnership.

A Irish key driver ofAll-Island successful developed web-based toolthat thatinterfaces interfaces aaweb-based tool greater problem if it runs past its course. developed causing systemic side-effects. genomics andproteomics. proteomics.

Commenting on the Taylor collaboration, Dr genomics and Innovation Awards.

The life-science SME, scientific research in 2010 is meaningful withthe theWaters Waters chromatography software with chromatography software Unresolved inflammation can lead to Explaining the novel anti-fibrotic effects Coulter said, “The collaboration with the Taylor Under normal conditions, the gastrointestinal founded by UCD pharmacology graduate, Dr interaction of academia with industry that package to improve and automate the export Researchers, Dr Natalia Artemenko and Dr Researchers, Dr Natalia and organ Dr package to clearly improve and automate export the development ofArtemenko fibrosis and seen, PhD student Emma Börgeson says, laboratory demonstrates thethe potential Ivan Coulter, has actively with ofdata data various file formats forsubsequent subsequent Matthew Campbell fromtherapeutic thecollaborated NationalInstitute Institute Matthew Campbell from the National of toto various file formats for that can be realised through focused failure with limited options ‘Fibrotic scar tissue forms when collagen Conway Fellow, Research Professor Cormac Taylor of Bioprocessing Research&& Training (NIBRT) analysis.The The modular architecture thetool tool of Bioprocessing Training (NIBRT) analysis. architecture ofofthe application ofmodular basic The development available togranted patients. is deposited at theresearch. site of inflammation. since being Science Foundation led by Fellow, Pauline also facilitates the ofon from led byConway Conway Fellow,aProfessor Professor PaulineRudd Rudd also facilitates themanipulation manipulation ofdata data from of a smart economy will depend like-minded We found that benzo-lipoxin significantly Ireland industryan research partnership award have developed open web-based other systems. have developed an openaccess, access, web-based otherdata datamanagement management systems.opportunities collaborative UCD researchers led by Conway Fellow, reduced thepartners amountidentifying of collagen laid in 2004. interface that interface thatfacilitates facilitatesextraction, extraction,querying querying and NIBRT realising basic and applied research The team are now working totointegrate Professor Catherine Godson believe down in our model and that collagen The NIBRT team are now working integrate The Irish Times award recognises the stellar and sharing of HPLC-glycan data generated in and sharing of HPLC-glycan data generated in synergies. Thiswith collaboration, initiated through GlycoExtractor the tackling unresolved inflammation may be GlycoExtractor withwas theEUROCarbDB EUROCarbDB gene expression reduced by both the innovative performance of Sigmoid Pharma in high throughput processes. high throughput processes. a SFI research supplement, highlights the totoprovide highframework provideaacomprehensive comprehensive highatheir viable therapeutic option indevelopment. renal fibrosis framework natural and synthetic lipoxin. application of research and potential that innovative indigenous companies Glycosylation the most common and throughput HPLC data analysis platform Glycosylation is thedeveloped most common and throughput HPLC data analysis platform for Meta-analysis by UCD researchers led by studies in humans have shown that nonfor and chronic isrenal disease including diabetic The company has two new drug working with academia can realise.” the storage and annotation of experimental structurally diverse post-translational Conway Fellow, Professor Denis Shields has progression was associated with gross the storage and annotation of experimental structurally diverse post-translational technologies, LEDDS™ and SmPill™, which not nephropathy.

Both LXA4 and benzo-LXA4 also caused data.

The integration ofwith generation modification proteins. than half Taylor’s collaboration Sigmoid Pharma has determined that there isMore noand clear evidence in the nefreducing gene. data.

The integration ofnext next generation modification ofthe proteins.

More than halfofofall allof only enhanceof solubility permeability adeletions trend towards renal cell death bioinformatic tools will further the metrics with gene products have been itshown to be locations certainly been successful by these that particular defective viral sequences in the drug but can deliver to targeted gene products have been shown to be bioinformatic tools will further thethe disease (CKD) and improve patient treatment, Conway researchers led by Dr. Tara In a recent edition of Faseb Journal, the and we think this may reflect fact However, much of the research in the area to glycosylated.

With many specific glycans development unified approaches for in two of May 2010.qxd:Layout 1 copy 07/05/2010 Page 3 ofof three co-authored publications to date thethe HIV-1 nef gene or certain regions ofor the in gastrointestinal tract, including the glycosylated.

With many specific or development unified approaches for McMorrow and Professor Michael Ryan have particular focus on arising from team describe the impact on aglycans model of13:12 with that the inflammatory milieu is initiatives being date has been based onCKD observational case glycoforms potential handling large scale glycomics data the highest ranking scientific journals inorthe protein playshowing a significant roleas incancer disease colon. glycoforms showing potential as cancer handling large scale glycomics data initiatives diabetes and hypertension.

The multisuccessfully secured €485,500 in funding as early renalthere fibrosis ofincreasing lipoxin (LXA4), and pushed to resolution by lipoxin inhibiting studies rather than rigorous, systematic biomarkers, is an need to with applications in biomarker discovery field, Gastroenterology and Proceeding of progression. biomarkers, there is an increasing need to with applications in biomarker discovery disciplinary research consortium has 25 the part of an overall award to the Systems its counterpart benzo-lipoxin, scientific evaluation.

This work as by doctoral the production ofofpro-inflammatory Thesynthetic Sigmoid Pharma-Taylor collaboration is develop high throughput, highly sensitive and National Academy Sciences, well This research was partially supported byas the develop high throughput, highly sensitive and partners (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney HIV-infected patients can be categorised on candidate Ravindra Pushker set out to developed bydevelopment Professor facilitating the of aGuiry, new Conway robust strategies that detail Pat the glycome of cytokines.’

This research was partially supported by generation of proprietary innovative products robust strategies that detail the glycome of from 15 countries and the project is due to set run Disease Diagnosis and Treatment (SysKid) the basis&ofDirector the number of it takes determine in a substantially larger sample therapeutic approach theyears treatment Fellow offorthe Centre foroffor and the creation of high-skilled jobs. for five years. consortium under the European Union FP7 them to progress to AIDS. Some patients if any association exists between disease inflammatory bowel disease (IBD) by bringing Synthesis & Chemical Biology. While the Professor Catherine Godson believes that, programme.

More than 15,000 people inamino and maintain the stable CD4 lymphocyte counts and progression and particular acid together research methodology of the anti-inflammatory effects of these lipid ‘Lipoxins may represent aIreland potentially The UCD Conway team, including postdoctoral millions of people worldwide living with the do not group go on with to develop AIDS even after more differences or deletions withinarethe nef gene.

Taylor the proprietary mediators have previously been described, useful therapeutic strategyand in Dr. renal researchers Dr. Craig Slattery Natalia Syskid (www.SysKid.eu) was established to symptoms IBD today. Current therapeutic than 10 years ofdrug infection. liquid/emulsion delivery system, the antieffects bykidney the On a per patient basis, there was no excess of Martin, will utilise cell culture and animal further ourfibrotic understanding offound chronic fibrosis.

We would hope to further options for this chronic debilitating disease are LEDDS®, developed by Sigmoid Pharma.

Scientists areare curious as to why these longLTNPlimited patients oneand oroften more defective nef researchers novel. investigate if with lipoxin its being analogues, very with surgery the only term,research non- progressor (LTNP) patientsDr do not sequences when compared to Commenting on Professor Taylor as well as to other lipid mediators, can most likely die a result of progressors. the raised New ledthe byaward, Conway Fellow viable option.

Theas Sigmoid product, currently develop Thisby may reflect differences in While the high frequency ofuniquely amino said, “WeAIDS. are delighted for Drthat Coulter and his Lipoxins stimulate the resolution glucose levels seen Breandán Kennedy indicates treatment most likely die asinstudy, adiabetes. result of the acid raised New research led Conway Fellow Dr accelerate recovery in progressive forms in a phase IIto clinical enables the host, genetics or environmental replacement at seen particular residues is indicative team and viral indeed it through reflects well onat our of diabetic blindness should of inflammation alook number glucose levels in diabetes.

Breandán Kennedy indicates that treatment of early renal oral delivery of afibrosis.’ powerful drug without Dr Kennedy and his team found that new factors thatthe could be exploited for of rapid systemic evolvement, permutation testing blood partnership.

A neurons key potentially driver of successful protecting responsible of diabetic blindness should look atfor colour causing side-effects. vessels and the neuronal cell death in new diabetic the treatment of the disease. showed that residues with more replacements Dr Kennedy and his team found that blood scientific research in 2010 is meaningful vision in thethe eye and notresponsible just targeting protecting neurons for the colour retinopathy arise independently Under normal conditions, the than expected were not statistically significant. vessels andcan the neuronal cell gastrointestinal death of in each diabetic interaction of eye academia with industry thatthe blood vessels as is currently the practice. cells, tissues and fluids.

Glycomics needs the supporting framework vision in the and not just targeting Studies in model organisms have shown that other.

In addition, theyindependently identified that of cone retinopathy can arise each of extensive, well-curated databases and blood vessels as people is currently theshows practice. infection with nef-deficient virus an The researchers conclude thatinvolved current data photoreceptor neurons, those in Nearly 2.5 million worldwide are blind Commercial packages that support HPLC other.

In addition, they identified that cone flexible analytical tools.

Currently, this field provides no evidence that individual residues attenuated course of infection and some instruments facilitate theinvolved extraction colour visioncannot and used inthose daylight, are most due to diabetic retinopathy.

This secondary photoreceptor neurons, in of Nearly 2.5 million people worldwide are blind of study lacks the established, results inbyboth academic outputs and the Irish biopharmaceutical development large quantities of data.

In an effort to affected the high glucose levels. complication ofBlanco diabetes activates the growth Dr has received the Dr Blanco established UCD Conway colour vision and used inthe daylight, arealleviate most dueAlfonso to diabetic retinopathy.

This data secondary comprehensive and centralised application of research toward clinical product company, Pharma recently scooped this bottleneck within high-throughput of new ISAC leakySigmoid blood vessels in the eye the and is 2011 Scholar award from flow cytometry core facility in 2004.

He collections, standards and information affected by the high glucose complication of diabetes activates the growth The research team made theirlevels. observations development with indigenous companies.” the overall for Innovation ofoffor the Year award at glycomic projects, the NIBRT team have responsible the death photoreceptors, International Society Advancement is the founder member and president reporting protocols that exist within of new leaky blood vessels in the eye and is using a novel zebrafish model of diabetes, theCytometry. inaugural Irish Times All-Island developed a web-based tool thatobservations interfaces the neurons that send visual messages of The 5-year ISAC to our of the Irish Cytometry Society and Dr The research team made their genomics and Commenting on the collaboration, responsible forproteomics. the death of photoreceptors, which resembles the Taylor early stages of diabetic Innovation Awards.

The life-science SME,to with the Waters chromatography software scholarship programme is designed aCoulter founder member of model the European brain. using a novel zebrafish of diabetes, said, “The collaboration with the Taylor the neurons that send visual messages to our retinopathy inNetwork. humans.

ItHe is designs an exciting founded bythe UCD pharmacology graduate, Dr enhance and leadership Cytometry and package to humans improve and automate the export Researchers, Drscientific Natalia and which resembles the early stages ofpotential diabetic Meta-analysis by UCD Artemenko researchers ledDr by studies in have shown that non laboratory clearly demonstrates the development for the group who now hope to Until now, it was unclear if the changes to brain.

Ivan Coulter, actively collaborated with potential ofhas emerging in this implements various cytometry education of data to various file formats forexciting subsequent Matthew Campbell from theleaders National Institute retinopathy inwas humans.

It is focused an Conwayand Fellow, Professor Denis Shields has progression associated with gross a that can be realised through further extend their research and establish vessels neurons occurred independently of Conway Fellow, Professor Cormac Taylor specialist field.

It provides valuable and training programmes and organises analysis.

The modular architecture of the tool of Bioprocessing Research & Training (NIBRT) development for thediabetic group disease. who hope to Until now,and it that was unclear ifnothe changes to is determined there is of clear evidence deletions inofthe nef gene. application basic research.

Thenow development model of late stage one other which type retinal neuron since being granted aProfessor Science Foundation training and mentoring opportunities national and international cytometry led Conway Fellow, Pauline Rudd also facilitates the manipulation of establish data froma further extend their research and vessels and neurons occurred independently thatbyparticular defective viral sequences in of of a smart economy will depend on like-minded Ireland industry research partnership award for awardees. meetings and conferences such as area to However, much of the research in the have developed an open access, web-based other management systems. the HIV-1 nef gene ortype certain regions of the modeldata of late stage diabetic disease. one other and which of retinal neuron is collaborative partners identifying opportunities in 2004.that facilitates extraction, querying date has been based on observational or case interface protein play a significant role in disease and NIBRT realising basic and applied research The team are now working to integrate studies rather than rigorous, systematic and sharing of HPLC-glycan data generated The Irish Times award recognises the stellarin progression. synergies. Thiswith collaboration, initiated through GlycoExtractor the EUROCarbDB scientific evaluation. This work by doctoral high throughput processes. innovative performance of Sigmoid Pharma in a SFI research supplement, highlights the framework to provide a comprehensive HIV-infected patients can be categorised on candidate Ravindra Pushker set out to high-

collaborator scoops Irish Times Innovation Award Lipoxins Conway attenuate renal fibrosis and Dr Roel Goldschmeding, University

Referenceof the gut leak out into surrounding Reference contents Medical Centre, Utrecht.

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well as an IRCSET Embark postgraduate

“When wescholarship applied theseto new drugsBörgeson.. to our IBD research Emma Bioinformatic analysis of HIV progression studies model, the gut was tricked into thinking that it Reference

Success in EU FP7 call

was being deprived of oxygen. This activated Lipoxin A4 and benzo-lipoxin A4 attenuate experimental protective pathways, which in turn prevented renal fibrosis. E Börgeson, N.G Docherty, M Murphy, K the deathRyan, of the cells that Guiry, line the Rodgers, R Goldschmeding, of HIV Anef areT O’Sullivan,P critical in determining the rate gastrointestinal tract,” explained D. F. Higgins, C Godson.

Faseb J. (E-pub)Professor May 31, 2011, of disease progression.

Professor Taylor.

“Our pre-clinical trial data canDenis now doi: 10.1096/fj.11-185017 Shieldsthe believes that searches for modifiers of inform next phase Sigmoid Pharma product progression ratesprocesses should now focus on other models to identify involved in early development pipeline”. hostprogression and viral factors.

“Systematic evaluation CKD and investigate novel Inofaddition to preventing the product that is currently large quantities of data byslowing bioinformatics strategies for and the in phase clinical studies, Sigmoid Pharma is can beII just as the important inThese refuting progression of disease. studies will NIBRT researchers Dr Matthew Campbell and Dr Natalia developing a that LEDDS™-enabled formulation ofas hypotheses current inepidemiological theand literature, be integrated withDrare clinical and NIBRT researchers Matthew Campbell Dr Natalia Artemenko who developed GlycoExtractor the inhibitor it ishydroxylase in across discovering unknown patterns”, he said.

Artemenko who developed GlycoExtractor studies the consortium using systems dimethyloxaloylglycine (DMOG) todevelop bring about biology methodologies in order to new This research wastargeted funded through Science effective, safe and delivery options of this to diagnostic strategies andUniversity treatment Foundation Ireland and College potentialCKD therapeutic agent.Email prevent development.

Dublin. tara.mcmorrow@ucd.ie for details of a PhD position currently available.

Zebrafish Zebrafish model model gives gives insights insights into into diabetic diabetic blindness blindness

Commenting on the research, Dr Kennedy Reference: Commenting research, DrHIV-1 Kennedy said, “By establishing a robust of model for early Meta-analysis to on test the the association nef amino and late stage diabetic retinopathy, we would said, “By establishing a robust model for early acid differences and deletions with disease progression.

Ravindra Pushker, Jean-Marcretinopathy, Jacquē, Deniswe C. Shields. hope to better the progression of and late stageunderstand diabetic would Journal of Virology, Apr 2010 p3644-3653 the disease and understand pave the way identifying of hope to better theforprogression EUROCarbDB, a research infrastructure design new targets for itsthe successful treatment”. the drug disease and pave way for identifying study funded by the EU 6th Framework new drug targets for its successful treatment”.

The research Prospective was funded users through Programme. canScience access the Foundation Ireland and Health Research GlycoExtractor tool funded on the through The research was tract is lined with cellsClinical that block theScience contents the 11th European Cytometry Board. http://glycobase.nibrt.ie:8080/DemoGlycoExtra Foundation Ireland and the Health Research of the gut from leaking into the intestine.

In an meeting, scheduled for the Convention ctor/mainPage.

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Yolanda Alvarez, Jenneth Chen, Alison of disease progression.

Professor Denis 2037–2041 hyperglycaemic model of non-proliferative diabetic Reynolds, Nore Waghorne, Johnreverse J. O’Connor, Breandan able to almost completely the Shields believes that modifiers retinopathy.

Yolanda Alvarez, Jennethfor Chen, Alison of Kennedy.

Disease Models &searches Mechanisms (2010) symptoms of the disease. progression should now focus on other Reynolds, Norerates Waghorne, John J. O’Connor, Breandan host and viral factors. evaluation Kennedy.

Models &“Systematic Mechanisms “When weDisease applied these new drugs(2010) to our IBD of largethe quantities data by model, gut was of tricked intobioinformatics thinking that it can being be justdeprived as important in refuting was of oxygen.

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GlycoExtractor advances glycan data manipulation

Conway collaborator scoops Irish Times Innovation Award ISAC Scholar award Bioinformatic analysis of HIV progression studies