Conway Focus Issue 12 Dec 2010

Centre of Excellence hosts international workshop dtimpeall. Is maith an rud e gur féidir plé Rinneamar cur sios agus plé ar gnáth

May 2010.qxd:Layout 1 copy development Irish biopharmaceutical Rinneadh agallamh ar 07/05/2010 ceathrar againn 13:12 Pharma recently ócompany, InstitúidSigmoid Mhic Con Mhí do chlár scooped nua the overall Innovation of the Year award at ar RTE Raidio na Gaeltachta le deanaí. the inaugural Irish Times All-Island As a Europeanchlár Centre ofseo Excellence, the Rachaidh darbh ainm Innovationan Awards. nua The life-science SME, Department of Rheumatology ingraduate, St Vincent’s ‘Ar StraebysaUCD tSaotharlann’ i ngleic leis an founded pharmacology Dr Ivan Coulter, hasan actively collaborated University Hospital was chosen to Labhair hostwith an eolaíocht agus timpeallacht.

Conway Fellow, Professor Cormac Sean MacFhearraigh, Sinead Nic An international two-day workshop onTaylor March since being granted a Science Foundation Ultaigh, Tiarnán Ó Máille agus mé féin 26th & 27th 2010.

Sponsored by Roche Ireland industry research partnership award faoin taighde éagsúil atá ar bun againn.

Pharma, the Participate workshop gave in 2004.

Labhraíomar neart réimsí taighde twenty from centres in ó The Irishrheumatologists Timesfaoi award recognises the stellar fiobrois scámhoige Alzheimer. innovative performance ofgalar Sigmoid Pharma Europe and Australiago the opportunity to in

their application of research and development. witness the care of patients with rheumatoid The company has developed two new drug arthritis (RA) LEDDS™ at St Vincent’s. technologies, and SmPill™, which not only enhance the solubility and permeability of the drug but can deliver it to targeted locations in the gastrointestinal tract, including the colon.

Irish biopharmaceutical development

Pagein 3 results both academic outputs and the application research toward lá agus naofrudaí a bhíonn arclinical siúl saproduct development with indigenous companies.”

tsaotharlann anseo san institúid don

The Participate focused ongoDr Commenting on programme theMhiníomar Taylor collaboration, lucht éisteachta. dóibh Coulter said, “The collaboration with the advanced treatment regimens for RAeolas in Taylor thea ndéanamar taighde áirithe chun laboratory clearly practical demonstrates theofpotential clinic,arincluding aspects biologic fháil na galair éagsúla chun coir leighis that can be realised focused infusion out through inna thedaoine accredited atherapy bhaintcarried amach bhionn application of basicdo research.

Theadevelopment suite that provides optimal care forlike-minded RA agafulaingt de bharr nadepend galair on seo.

Tá anof smart economy will patients.

In addition to lectures from collaborative partners identifying opportunities chuid taighde tabhachtach ar siúl Conway anseo Fellows, Professors Oliver FitzGerald and and realising basic and applied research san institiúd a d’fhéadfadh tionchar synergies.

This collaboration, initiated through Douglas Veale, delegates heard from clinical mhor a bheithsupplement, aige ar shaol daoinethe inár anurse SFI research highlights specialists about patient education, potential that innovative indigenous companies screening and monitoring of biological working with academia can realise.”

tract is lined with cells that block the contents ofa the gut from ar leaking into theseo intestine.

In an dhéanamh an taighde tri mhean IBD patient, this barrier is broken and the na Gaeilge le mhuintir na Gaeilge. Bígí ag contents of the gut leak out into surrounding Addressing the international guests, Mary faire amach don chlár nua ‘IsConway eolaíMsmise’ areas.

The research team in UCD used Duff, Director of Nursing and Kayclass Radio inaMs. dteannta is of aar model of na IBDGaeltachta, and, by applying a new Connolly, Assistant Directorinhibitors, of http://www.

Nursingwere for the drugs known as hydroxylase féidir é a fháil ar podcast ar able to & almost reverse Bone Joint completely Unit expressed theirthehope that rte.ie/rnag/arstraesatsaotharlann.html symptoms of theof disease. the experience the multidisciplinary team

from St wouldnew provide template “When weVincent’s applied these drugsa to our IBDfor model, the gut was tricked into thinking delegates to reproduce similar care andthat it Robert Lumsden was being deprived of oxygen. This activated facilities for the management of RA patients in protective pathways, which in turn prevented their respective countries. the death of the cells that line the gastrointestinal tract,” explained Professor Taylor. “Our pre-clinical trial data can now inform the next phase Sigmoid Pharma product development pipeline”.

Guiding Conway scientists through the glycan maze Award collaborator scoops Irishanalysis Times Innovation therapies.

Taylor’s collaboration with Sigmoid Pharma has certainly been successful by these metrics with three co-authored publications to date in two of In addition to the product that is currently in the highest ranking scientific journals in the tract lined cells that block the contents results in both academic outputs and the Postdoctoral researchers from the features of therapeutic the is type ofwith data each provides. phase II clinical studies, Sigmoid Pharma is field, Gastroenterology andglycoproteins Proceeding of and the of the gut from leaking into the intestine. In an application of research toward clinical product company, Sigmoid Pharma recently scooped The Sigmoid Pharma-Taylor collaboration is National Institute for Bioprocessing to establish connections between developing a LEDDS™-enabled formulation of National Academy of Sciences, as well glycan as the IBD patient, this barrier is broken development with indigenous companies.” the overall Innovation of the Year award at facilitating the development of a new Research & Training, under the structure and their functions.

They classify the approaches and the the hydroxylase inhibitor generation of proprietary innovative products contents of the gut leak out into surrounding the inaugural Irish Times All-Island therapeutic approach for the treatment of supervision of Conway Fellow, dimethyloxaloylglycine (DMOG) to are bring and the creation of high-skilled jobs. according to whether glycans in about Commenting on the Taylor collaboration, Dr areas. The research team in UCD Conway used Innovation Awards.

The life-science SME, inflammatory bowel disease by bringing Professor Pauline Rudd, (IBD) published a Dr effective, safe and targeted of this However, face a number intact glycoproteins, aredelivery chemically, Coulter said,researchers “The collaboration with the Taylor a model of IBD and, by applying a new class of founded the

by UCD pharmacology graduate, More than 15,000 people in Ireland and together research methodology of the potential therapeutic agent.glycans or are review ofofavailable technologies laboratory clearly the potentialthe of challenges in demonstrates relation glycan enzymatically released An image the peptide structurefor central variety of in ordertoto drugs known as hydroxylase inhibitors, were Ivan Coulter, hasfrog actively collaborated with millions of solutions people worldwide areunderstand living with the Taylor group with the proprietary that can be realised through focused protein glycosylation analysis in the analysis primarily to the diversity glycoproteins themselves.

Each to the work of adrug UCDdelivery Conway research team able to almost completely reverse theapproach Conway Fellow, Professor Cormac Taylor structural basis for due the difference in biological symptoms IBD today.

Current therapeutic liquid/emulsion system, application of basic research.

The development October issue of Nature Chemical of molecular structure, construction can give complementary information so symptoms of the disease. since being granted afront Science options for this chronic debilitating disease are was selected as the by coverFoundation image for the LEDDS®, developed Sigmoid Pharma. activity. of a smart economy will depend on like-minded Biology. sequence extent of possible it is important at the outset to decide Ireland industry research partnership award very limitedand withthe surgery often being the only April 2010 edition of the scientific journal, “When we applied these new drugs to our IBD collaborative partners identifying opportunities Commenting on the award, Professor Taylor linkages withThe lipids or peptides. the level of data required, whether in 2004. viable option.

Sigmoid product, currently Thisrealising particular XT-7 peptide, from the Biochimica Biophysica (BBA);and his model, the gut was tricked into thinking that it and basic and appliedisolated research said, “We areetdelighted for Acta Dr Coulter Additionally, naturally quantitative or qualitative data is needed in a phase II clinical study,occurring uniquely enables for Glycosylation, the most common postThe Irish Times award recognises the stellar skin of Silurana tropicalis, shows potential was being deprived of oxygen. This activated synergies. This collaboration, initiated through Proteins Proteomics. team and & indeed it reflects well on our oral delivery of aare powerful drug without glycoproteins typically only present and how much biological material is translational modification conferred innovative performance of Sigmoid Pharma in protective pathways, which in turn prevented adrug SFI research supplement, theactivity as it hashighlights impressive partnership. A key driver of successful causing systemic side-effects. at lowdevelopment levels and, currently, therecompanies is no available their application of research and development. on proteins, is skin the feature that most Peptides in the many species of frog the death offor theanalysis. cells that line the potential thatgrowth innovative indigenous scientific research in of 2010 is meaningful against the of bacteria and Candida universal method for can rapid and reliable The has developed two new drug influences the function of industry proteins gastrointestinal tract,” explained Professor working with realise.” havecompany anti-bacterial and anti-fungal properties normal conditions, the gastrointestinal May 2010.qxd:Layout 1academia copy 07/05/2010 Page 3 academia interaction of with that 13:12 Under albicans.

However, this potential as an antitechnologies, LEDDS™ and SmPill™, which not identification of glycan structure. and their Due to This work made trial possible through Taylor.

“Our was pre-clinical data can now as well as biological thethe ability toactivity. lyseand or rupture Taylor’s with Sigmoid Pharma has only enhance solubility permeability of infectivecollaboration agent is restricted by its haemolytic their diversity, glycans are finely-tuned funding Science Foundation inform thefrom next phase Sigmoid Pharma product mammalian cells.

This innate immunity certainly been successful by these metrics with the drug but can deliver it to targeted locations Inactivity. reality, it is the research goals of development information carriers and there is now of a Ireland, thepipeline”.

EU FP6 Glyfdis and Eurospan protects it from attack.tract, These properties three co-authored publications to date the in two of in the gastrointestinal including the the particular project that dictate renewed emphasis on their analysis. programmes, the Royal Society and In addition to the product that is currently in the highest ranking scientific journals in the colon. frog skin peptides are exciting from the A change to the amino acid structure of the most appropriate method of analysis.

ChiefIIScientific OfficeSigmoid of the Scottish phase clinical studies, Pharma is field, Gastroenterology and Proceeding of the prospect of being developedcollaboration into Researchers must not only be aware XT-7 peptide can create an analogue Government.

The Sigmoid Pharma-Taylor is With specific changes in the glycosylation developing a LEDDS™-enabled formulation of National Academy of Sciences, as wellthat as the therapeutically valuable anti-infective and antiof the techniques available but facilitating the development of & a new retains anti-infective properties butwhat without the process occurring in health disease, the hydroxylase inhibitor generation of proprietary innovative products Reference cancer agents. therapeutic approach the treatment information these techniques or glycan analysis can for provide both of dimethyloxaloylglycine (DMOG) to bring about and the creation of high-skilled jobs. complicating haemolytic activity.

The single A systematic approach to protein glycosylation inflammatory bowel disease (IBD) by bringing Meta-analysis by UCD researchers led by of HIV areand critical in maze. determining the studies in humans have shown that non combination of techniques will provide. effective, targeted delivery thisrate diagnostic and Dr prognostic information. analysis:nef asafe path through the Karina of Mariño, amino acid15,000 substitution (glycine replaced by Conway Fellow, Fellow, Chandralal Hewage andhas his More than people in Ireland and together the research methodology of the Conway Professor Denis Shields of disease progression.

Professor progression was associated with gross The authors succinctly stratify the major potential therapeutic Jonathan Bones, Jayesh agent.

J Kattla, & PaulineDenis M It is also useful in drug discovery and millions ofinpeople worldwide arefor living withofthe lysine) improves the therapeutic potential team carried out there molecular of the Taylor groupthat with the proprietary determined is nomodelling evidence Shields searches for modifiers of deletions theroutinely nef gene. technologies used structural Rudd.

Biology (October 2010) CoverNature ofbelieves AprilChemical 2010that edition of Biochimica et Biophysica production to comply withclear regulatory symptoms IBDoccurring today. Current therapeutic liquid/emulsion drug delivery that particular defective viralsystem, sequences in a progression rates should now focus on other XT-7 peptide and its analogue [G4K]XT-7 in this naturally peptide. doi:10.1038/nchembio.437 Acta (BBA); Proteins & Proteomics.

Nand O-glycan analysis and describe requirements for monitoring critical However, of the research in the area to options formuch this chronic debilitating disease are LEDDS®, developed Sigmoid Pharma. the HIV-1 nef gene orbycertain regions of the host and viral factors. “Systematic evaluation date limited has been based on observational or only case very with surgery often being the protein play a significant role in disease of large quantities of data by bioinformatics Commenting on the award, Professor Taylor studies rather than rigorous, systematic viable option.

The Sigmoid product, currently progression. can be just as important in refuting said, “We are delighted for Dr Coulter and his scientific This work by doctoral in a phaseevaluation.

II clinical study, uniquely enables hypotheses that are current in the literature, as team and indeed it reflects on our on HIV-infected patients can bewell categorised candidate Ravindra Pushker set out to oral delivery of a powerful drug without it is in discovering unknown patterns”, he said. partnership.

A key driverof ofyears successful the basis of the number it takes for determine in a substantially larger sample set causing systemic side-effects. scientific researchto in AIDS. 2010 is meaningful them to progress Some patients if any association exists between disease This research was funded through Science Under normal conditions, the gastrointestinal interaction of academia with industry that maintain stable CD4 lymphocyte counts and progression and particular amino acidthe Foundation andthat University College tract is lined Ireland with cells block the contents results in both academic outputs and Irish biopharmaceutical development will examine whether vitamin D2 In an Conway DrPharma Lorraine Brennan and nmol/l is prevalent intoward as much of do not goFellow, on to develop AIDS even after more differences orresearch deletions within the as nefhalf gene. ofDublin. the gut from leaking into the intestine. application of clinical product company, Sigmoid recently scooped enhanced mushrooms can actually UCD colleagues, Dr Anne andat European and USindigenous populations.

There is thanoverall 10 years of infection.

IBD patient, this barrier is broken and the development with companies.” the Innovation theNugent Year award On a per by patient basis, there excess of A new fortnightly forumoffor Conway graduate decided the members butwas it isno envisaged (thomas.scharzl@ucd.ie ) and postdoctoral increase ofsurrounding vitamin D Professor Mike Gibney from the Institute accumulating evidence suggest thatnef contents ofcirculating the gut leaklevels out into the inaugural Irish Times All-Island Scientists are curious as to why these longLTNP patients with one orofto more defective and postdoctoral researchers will be launched that it will include a mix technology researchers, Dr David Commenting on the Taylor collaboration, Dr areas.

The research teamGomez in aUCD Conway used Innovation Awards.

The life-science SME, (25(OH)D) and provide novel vehicle of Food and Health have been awarded vitamin D status may play a role in the term, nonprogressor (LTNP) patients do not sequences when compared to progressors.

Coulter said, “The collaboration with the Taylor in May 2010.

Thispharmacology initiative will give early- Dr overviews, informal and formal research (david.gomez@ucd.ie) and Dr Craig Slattery aReference: model of IBD and, byof applying a new class of founded by UCD graduate, for dietary delivery vitamin D. funding from Monaghan Mushrooms development of diseases those develop AIDS. This may reflect differences in While the high frequency of beyond amino acid laboratory clearly demonstrates the potential stageCoulter, researchers the opportunity to talkwith about seminars, PhD viva rehearsals and career (craig.slattery@ucd.ie ) invite for Meta-analysis test the association ofsuggestions HIV-1 nefwere amino drugs knowntoas hydroxylase inhibitors, Ivan has actively collaborated theperform host, viralresearch genetics or environmental replacement at particular residues is indicative that can be through focused to their vitamin D related to realised bone acid and deletions with disease progression. able to almost completely reverse the Conway Fellow, Professor Cormac Taylor sciencethat and issues thaton concern them in an development talksmetabolism. from within and beyond thedifferences forum schedule. factors could potentially be exploited for of rapid evolvement, permutation testing application of basic research. The development Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields. enhanced mushrooms. symptoms of the disease. since being granted a with Science Foundation informal environment refreshments academia.

Forum committee members, PhD the treatment of the disease. showed that residues with more replacements Journal of Virology, Apr 2010 p3644-3653 of a smart economy will depend on like-minded Meta-analysis byresearch UCD researchers by of HIV nef are critical in determining the rate studies have shown that non There isinMr ahumans real need forstatistically enhancing Ireland industry partnership provided!

Content for the forum willled beaward student Thomas Schwarzl than expected were not significant.

“When we applied these new drugs to our IBD collaborative partners identifying opportunities Conway Fellow, Professor Denis Shields has of disease progression.

Professor Denis progression was associated with gross Studies in model organisms have that in 2004.

The major source of vitamin Dshown is dietary intake and vitamin Dresearch 2 enhanced model, gut was tricked into for thinking that itof and realising basic and applied determined that there recognises is novirus clear evidence Shieldsthe believes that searches modifiers deletions in the nef gene. infection with nef-deficient shows an The researchers conclude that current data The Irish Times award the stellar sunlight with defective diet providing a limited in mushrooms represent a novel vehicle was being deprived of oxygen. synergies.

This collaboration, initiated through that particular viral sequences progression rates should now This focusactivated on other provides no evidence that individual residues attenuated course of infection and some innovative performance of Sigmoid Pharma in However, muchsupplement, of the research in the the area to source.

Vitamin Dor deficiency, reflected vitamin D intakes. protective pathways, which in turn prevented afor SFIincreasing research highlights the HIV-1 nef gene certain regions of the host and viral factors.

“Systematic evaluation their application of research and development. date has that been basedtheir on indigenous observational or case the deathquantities of the cells that line the potential innovative companies by circulating 25-hydroxyvitamin D However, to date, efficacy has protein play a significant role in disease of large of data by bioinformatics The company has developed two new drug studies rather than rigorous, systematic gastrointestinal tract,” explained Professor working with academia can realise.” progression.concentrations can be just as important in refuting [25(OH)D] less than 50 not not been demonstrated. This study technologies, LEDDS™ and SmPill™, which scientific evaluation. This work by doctoral Taylor.

“Our pre-clinical trial data can now hypotheses that are current in the literature, as Taylor’s collaboration with Sigmoid has only enhancepatients the solubility permeability HIV-infected can beand categorised on of candidate Ravindra Pushker set outPharma to inform the next phase Sigmoidpatterns”, Pharma product it is in discovering unknown he said. certainly been by larger these metrics with the cannumber deliver it targeted locations the drug basisbut of the ofto years it takes for determine in asuccessful substantially sample set development pipeline”. three to date in two of in the to gastrointestinal tract,Some including the them progress to AIDS. patients if anyco-authored association publications exists between disease This research was funded through Science InFoundation addition toIreland the product that is currently the highest ranking scientific journals in the colon. maintain stable CD4 lymphocyte counts and progression and particular amino acid and University Collegein phase II clinical studies, Sigmoid Pharma is field, Gastroenterology Proceeding of the do not go on Pharma-Taylor to develop AIDS even after more differences or deletionsand 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 On a per patient basis, there was noproducts excess of the hydroxylase inhibitor generation of proprietary innovative therapeutic approach thewhy treatment of Scientists are curious for as to these longLTNP one or morejobs. defective nef dimethyloxaloylglycine (DMOG) to bring and thepatients creationwith of high-skilled Elaineabout Quinn inflammatory bowel disease (IBD) by bringing term, non- progressor (LTNP) patients do not sequences when compared to progressors. effective, safe and targeted delivery of this Communications & Education Officer More than 15,000 people in Ireland and Reference:therapeutic agent. together the research methodology of the in develop AIDS. This may reflect differences While the high frequency of amino acid potential Meta-analysis to test the association of HIV-1 nef amino Conway of Biomolecular & Biomedical Research millions of people worldwide are living with the Institute Taylor group the proprietary the host, viralwith genetics or environmental replacement at particular residues isUCD indicative acid differences and deletions with disease progression. symptoms IBD today. permutation Current therapeutic liquid/emulsion drug delivery be system, University College Dublin factors that could potentially exploited for of rapid evolvement, testing Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields. options chronicwith debilitating disease are LEDDS®, developed

by Sigmoid Pharma.

Belfield, Dublin 4 the treatment of the disease. showedfor thatthis residues more replacements Journal of Virology, Apr 2010 p3644-3653 very with surgery often beingsignificant. the only than limited expected were not statistically Ireland Commenting on the award, Professor Taylor Investing Your Future Studies in in model organisms have shown that viable option. The Sigmoid product, currently said, “We are delighted for Dr Coulter and his infection with nef-deficient virus shows an The researchers conclude current data in a phase II clinical study, that uniquely enables E: elaine.quinn@ucd.ie team and indeed reflects welland on some our provides no of evidence that drug individual residues attenuated courseit of infection oral delivery a powerful without T: (+353-1) 716 6706 partnership. A key driver of successful causing systemic side-effects.

F: (+353-1) 716 6701 scientific research in 2010 is meaningful Under normal conditions, the gastrointestinal interaction of academia with industry that W: www.ucd.ie/conway

Frog peptide structure selected for journal cover

Bioinformatic analysis of HIV progression studies

Conway collaborator scoops Irish Times Innovation Award Investigating effects of vitamin–D enriched mushrooms in the diet Launch of Conway postdoctoral &2 graduate forum Bioinformatic analysis of HIV progression studies

December 2010 Issue May 2010 Issue 10112 september 2007 Issue

Conway collaborator scoops Irish Times Innovation Award Is Eolai Mise

Success in EU FP7 call disease (CKD) and improve patient treatment, Conway researchers led by Dr. Tara McMorrow and Professor Michael Ryan have with particular focus on CKD arising from May 2010.qxd:Layout 1 copy 07/05/2010 13:12 3 diabetes and Page hypertension.

The multisuccessfully secured €485,500 in funding as disciplinary research consortium has 25 part of an overall award to the Systems partners (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney from 15 countries and the project is due to run Disease Diagnosis and Treatment (SysKid) for five years. consortium under the European Union FP7 programme.

The UCD Conway team, including postdoctoral researchers Dr. Craig Slattery and Dr. Natalia Syskid (www.SysKid.eu) was established to Martin, will utilise cell culture and animal further our understanding of chronic kidney

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

GlycoExtractor advances glycan data manipulation Success in EU FP7 call Glycomics needs the supporting framework cells, tissues and fluids.

EUROCarbDB, a research infrastructure design study funded byInnovation the EU 6th Framework Award of extensive, well-curated databases and Conway collaborator scoops Irish Times Commercial packages2that support HPLC Worm research reveals cilia disease gene function Role for CO sensor identified flexible analytical tools. Currently, thiscellular field Programme.

Prospective users can access the

models to identify processes involved in early disease (CKD) and improve treatment, Conway researchers led by Dr. Tara instruments cannot facilitatepatient the extraction of of study lacks the established, GlycoExtractor tool CKD progression andoninvestigate novel McMorrow and Professor Michael Ryan have with particular focus on In CKD arising from large quantities of data. an effort to alleviate http://glycobase.nibrt.ie:8080/DemoGlycoExtra comprehensive and centralised data strategies for preventing and slowing diabetes and hypertension.

The multithis bottleneck within high-throughput successfully secured €485,500 in funding as tract is lined with cells that the contents results in both academic outputs and the Irish biopharmaceutical development UCD Conway researchers have found CO sensor associated with antiof articles published in block thethe issue of 2 collections, standards and information ctor/mainPage.

Research by Fellow, the function of worm Arl13b causesproduct the progression complex including diabetes, thetraits disease.

These studies will In an disciplinary research has 25 clinical part of anprotocols overall award to Conway the Systems glycomic theconsortium team have of theof gut from intoobesity, the intestine. application ofNIBRT research toward company, Sigmoid Pharma recently scooped that carbon dioxide (CO )Dr is Oliver not only projects, inflammatory and immunosuppressive the Journal ofleaking Immunology; a further reporting that exist within Reference 2 with clinical and Blacque has revealed ciliary membrane to bulge and become be integrated mental retardation andepidemiological even cancer. developed adevelopment web-based tool that interfaces (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney IBD patient, this barrier broken and the with indigenous companies.” the overall Innovation ofnew the information Yearand award at A web-based of interface for high genomics and involved proteomics. in climate change apartners signalling may exist.

We found that GlycoExtractor: endorsement the isusing research. across the with the Waters chromatography about a gene implicated in Joubert from misshapen as well as software affecting of contents of consortium the gut leak out intosystems surrounding the inaugural Irish Times All-Island 15 countries and the project is due tothe runabilitystudies Disease Diagnosis and Treatment (SysKid) processing of HPLC-Glycan data throughput on the Taylor collaboration, Drbiology waste product of respiration inSME, cells elevated levels of COthe had a profound Dr Oliver hopes these findings in P. order to develop new package to Commenting improve and automate export Researchers, Dr Natalia Artemenko and Dr 2 distribute Natalia V.methodologies Artemenko, Matthew Campbell, and Pauline areas.

The Blacque research team inthat UCD Conway used Innovation Awards.

The life-science for five years. consortium under the European Union FP7 syndrome and related cerebellar disorders other proteins to collaboration properly within Coulter said, with the Taylor diagnostic strategies and treatment options M. Rudd Journal of of Proteome Research, 2010, 9 ppclass but alsobycharacterised plays an active role in regueffect on a “The master pathway part ofIBD their wider programme of of will ultimately lead to applying a greater Matthew Campbell from the National Institute ofbone data to various file formats forsignalling subsequent aAs model and, by a (4), newto founded UCD pharmacology graduate, Dr programme.

(JSRDs), by blindness, the ciliary membrane. laboratory clearly demonstrates the potentialprevent 2037–2041 The Conway team, including postdoctoral CKD development.

Email analysis. modular architecture ofEoin the tool of Bioprocessing Research & Training (NIBRT) understanding only of JSRDs, butwere also lating the genes involved in inflamcalled NF-ĸB”, said Dr Cummins, research, Professor Cormac Taylor drugs known as not hydroxylase inhibitors, Ivan Coulter, has actively collaborated with UCD The abnormalities, cystic kidneys, that can beSlattery realised and through focused researchers Dr.the Craig Dr. Natalia Syskid (www.SysKid.eu) was established to tara.mcmorrow@ucd.ie forciliopathies detailsreverse of asuch PhD led

by Conway Fellow, Professor Pauline Rudd also facilitates manipulation of data fromlead able to almost completely theaas Conway Fellow, Professor Cormac Taylor They also found that a fully functional of closely related mation and innate immunity.

Their postdoctoral researcher and and Dr. Eoin Cummins hosted 2-day developmental delay and loss of muscle application of basic research.

The development Martin, will utilise cell culture and animal position currently available. further our understanding of chronic kidney have developedsince an open other data management systems. symptoms of the disease. beingaccess, grantedweb-based awere Science Foundation Arl13b protein ispublication. needed for the Meckel Gruber and Bardet-Biedl syndrome, research findings highlighted in author oneconomy this conference that focused on therapeutic of a smart will depend onnormal like-minded tone and control.

The findings of this interface that facilitates extraction, querying Ireland industry research partnership award st functioning of a protein transport system in as well as perhaps more common The NIBRT team are now working to integrate “When we applied these new drugs to our IBD collaborative partners identifying opportunities aspects of hypoxia-inducible pathways. the October 1 issue of the Journal of a Science and sharing of research, HPLC-glycan datathrough generated in in 2004. funded GlycoExtractor with EUROCarbDB cilia.

Thisthe intraflagellar transport system phenotypes with model, the gutassociated was tricked intocilium thinking and realising basic and applied research Sponsored by the HypoxiaNET EUthat it Immunology.

In previous work, the Taylor group high throughput processes.

Foundation Ireland President of Ireland The Irish Times award recognises the stellar framework synergies. to provide a comprehensive highwas being deprived ofmeeting oxygen. retardation This activated This collaboration, initiated through (IFT) makes contact with the ciliarymaster dysfunction such as mental and COST action, the attracted demonstrated that the NF-ĸB Young Researcher Award (PIYRA) to Oliver of Sigmoid Pharma in Glycosylation isinnovative the mostperformance common and throughput HPLC data analysis for protective pathways, which in turn prevented amembrane.

SFI research supplement, highlights the Based onplatform these results, they obesity. more than 100 scientists from Europe, The of oxygen (O ) and carbon signalling is induced by their levels application of research Blacque, were recently published in the the storagepotential 2and development. and annotation of experimental structurally diverse post-translational the death of the cells that line the thatpathway innovative indigenous companies proposed a newOworking model for Arl13b, The company has developed new drug the USA “That and Korea toassociates UCD Professor Conway dioxide (CO ) in cells vary hypoxicwith (low ) conditions. of Cell modification ofJournal proteins.

More than halfcan oftwo all data. The integration of next gastrointestinal tract,” explained working academia can realise.”In this He notes Arl13b with ciliary 2 Biology.

2generation Glycomics needs the supporting framework cells, tissues and fluids.

EUROCarbDB, a research infrastructure design where it functions at the ciliary membrane th technologies, LEDDS™ and SmPill™, which not bioinformatic tools will further the gene products dramatically have been shown to be Institute October 7th & 8can 2010. in health and in diseases study, the researchers now show that Taylor.

“Ouron pre-clinical trial data now membranes and is required for of extensive, well-curated databases and study funded by the EU 6th Framework cilium Taylor’s collaboration with Sigmoid Pharma has only enhance the solubility and permeability of One of seven genes associated with JSRDs, to regulate important ciliary membrane development of unifiedprotein approaches for within this glycosylated. With many specificinflammation, glycans or inform the next phase Sigmoid Pharma product Commercialapackages that support HPLC The delegates heard and discussed such as but chronic ischemia central regulator structure/function in both worms and Programme.

Prospective users can access the flexible analytical tools.

Currently, this field certainly been successful by these metrics with the drug can deliver it to targeted locations Arl13bpotential codes forasacancer already known to large properties such asthe shape, transmembrane handling scale facilitate glycomics data initiatives glycoforms showing development pipeline”. instruments cannot extraction oflevels inGlycoExtractor the latest basic science,thetechnology, cancer whereprotein metabolism rates pathway, IKKα reacts to CO tooldemonstrates on of study lacks and thethe established, mammals remarkable three co-authored publications to date in two of in gastrointestinal tract, including the 2 biomarkers, there isroles an increasing need toand/or function with biomarker discovery play in the formation protein distributions and IFT. largeapplications quantities ofindata.

In an effort alleviate comprehensive and centralised altered. data http://glycobase.nibrt.ie:8080/DemoGlycoExtra pharmacology and translational are significantly Elevated CO a rapid, reversible andtodose dependent In addition to the product that currently in the highest ranking scientific journals in theNIBRT colon. evolutionary conservation ofis how this small researchers Dr Matthew Campbell and Dr Natalia develop high throughput, highly and this2bottleneck within high-throughput of cilia, which are sensitive hair-like projections collections, standards and information ctor/mainPage.

This research was partially supported by phase II clinical studies, Sigmoid Pharma is field, Gastroenterology and Proceeding of the Artemenko who developed GlycoExtractor medicine aspects of this hot topic in levels that occur during hypoventilation manner.

Up to only 20 years ago, many believed G-protein functions.” robust strategies that detail the glycome of glycomic projects, the NIBRT team have The Sigmoid Pharma-Taylor extending from the surfacecollaboration of the cell. is reporting protocols that exist within a LEDDS™-enabled formulation of National Academy of Sciences, as well as theReferencedeveloping hypoxia research. of intubated patients have found cilia to tool be redundant cellular amost web-based that interfaces facilitating the precise development of a been new A web-basedinhibitor interface for high genomics and However, proteomics. the molecular detailsdeveloped of Reference the hydroxylase generation of proprietary innovative productsGlycoExtractor: with the Waters chromatography software organelles that have fallen victim to to decrease mortality associated with Commenting the significance processing of HPLC-Glycan data at therapeutic approach fordoing the treatment of Joubert syndrome Arl13b functions dimethyloxaloylglycine (DMOG) tociliary bring about and the creation on of high-skilled jobs. of throughput what exactly Arl13b is in cilia have Researchers, Dr Natalia Artemenko and Dr package to improve and automate the export V. Artemenko, Matthew P. Campbell, and Pauline Natalia inflammatory bowel disease by bringing mammalian evolution - a type said, of cellular acute respiratory distress(IBD) syndrome or the research, Dr Cummins “The M. Rudd Journal membranes andand stabilizes protein transport in effective, safe targeted delivery of pp this remained unclear. of Proteome Research, 2010, 9 (4), Matthew Campbell from the National Institute of data to various file formats for subsequent More than 15,000 Ireland and together the research methodology ofinjury. the Caenorhabditis elegans.agent.

Cevik S, Hori Y, Kaplan OI, appendix.

We nowpeople knowinthat these cellular endotoxin-induced acute lung molecular mechanism of this CO potential therapeutic 2037–2041 2 analysis. The modular architecture of the of Bioprocessing Research & Training (NIBRT) millions of people worldwide aretool living with the Kida K, Toivenon T, Foley-Fisher C, Cottell D, Katada T, Taylor group with the proprietary Blacque’s team studied the gene in thealso ciliafacilitates antennae present on of nearly all of our cells sensor may an alternative led by Conway liquid/emulsion Fellow, Professor the manipulation data from symptoms IBDprovide today. Current therapeutic Kontani K, Blacque OE. J Cell Biol. 2010 Mar 22; drugPauline deliveryRudd system, of tiny worms (Caenorhabditis elegans) and serve fundamental roles in many COdeveloped sensing a feature of other data management therapeutic route indebilitating those instances have developedAcute an open access, web-based systems. options for this chronic disease are 188(6):953-69 LEDDS®, byisSigmoid Pharma.

2 on the research, Dr Kennedy to die asand a result of the raised including Commenting New research led bycollaborators Conway Fellow Dr University while the ofmost likely very motility sensory functions, interface that facilitates extraction, querying specialised cells inintreatment lower animal species when suppressing the body’s innate limited with surgery often being the only The NIBRT team are now working to integrate glucose levels seen in diabetes.

Breandán Kennedy indicates that said, “By establishing a robust model for early Commenting ondata theparallel award, Professor Taylor conducted experiments in signalling pathways critical to development. and sharing of Tokyo HPLC-glycan generated in viable option.

The Sigmoid product, currently May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3 such asshould flies and littleGlycoExtractor immune system or inflammatory and late stage diabetic retinopathy, we would with the EUROCarbDB of diabetic blindness lookrodents at for Dr but said, “We are delighted Coulter his high throughput processes. a phase IIisclinical study, uniquely enables cultured human Together, theyand Dr Kennedyin and his team found that new blood known aboutitcells. the effect response clinically desirable.

We framework to provide a comprehensive highprotecting the is neurons for colour team and responsible indeed reflects wellof onaltered our vessels It is now not surprising that defects oral delivery of a powerful drug withoutin hope to better understand the progression of and HPLC the neuronal cell death in diabetic confirmed that Arl13b proteins uses lipid Glycosylation is the most common and throughput data analysis platform for vision in the eye and not just targeting the CO onled gene expression.

This research now need to decipher the exact the disease and pave the wayinvolved for identifying partnership.

A key driver disease (CKD) and improve patient treatment, models to identify processes in early Conway researchers by Dr. Tara of successful cilium structure and function are associated 2 causing systemic side-effects. retinopathy can arise independently of each anchors to associate withfellow, ciliary structurally diverse the storage and annotation experimental blood vessels asProfessor ispost-translational currently the scientific research in practice.

2010 isthe meaningful CKD investigate novel new progression drug targets and for its successful treatment”.

McMorrow and Michael Ryan have with particular focus onidentified CKD arising from group, led by Conway Professor mechanisms ofofthis CO -dependent with an ever expanding range of human other.

In addition, they that cone 2 modification ofmembrane. proteins. More than half ofindustry all data. Theand integration of next generation Under normal conditions, the gastrointestinal interaction of academia withblind that strategies for preventing and slowing the diabetes hypertension.

The multisuccessfully secured €485,500 in funding as effect Cormac Taylor examined the of intracellular signalling pathway”. photoreceptor neurons, those involved in Nearly 2.5 million people are diseases andfurther syndromes, called The researchofwas Sciencewill bioinformatic tools will thehas collectively gene products have been worldwide shown to be progression the funded disease.through These studies disciplinary research consortium 25 partto ofdiabetic an overall award towork the Systems colour vision and used in daylight, are most due retinopathy.

This secondary altered CO levels on gene expression in Much of the on the project was carried ciliopathies, which have overlapping clinical Foundation Ireland and theand Health Research development of unified approaches for glycosylated. With many specific glycans or 2 be integrated with clinical epidemiological partners by (16the universities, 9 industry partners) Biology towards Novel Chronic Kidney high glucose levels. complication ofout diabetes the growth mammalian cells against a background The work, which was by and studies by potential UCDactivates doctoral candidate, Sebihaaffected features such as polycystic kidneys glycoforms showing as cancer handling large scale glycomics datafunded initiatives Board. across the consortium using systems from 15 countries and the project is due to run Disease Diagnosis and Treatment (SysKid) of new leaky blood vessels in the eye and is biomarkers, there is an increasing need to went onThe with applications biomarker discovery of inflammation.

Science Foundation Ireland and the biology methodologies Cevik.

She and herUnion colleagues tofive livers, retinal degeneration, bone research teamin made their observations in order toEU develop new Delegates at the HypoxiaNET COST action for years. consortium under European FP7 responsible the the death of photoreceptors, NIBRT researchers Dr Matthew Campbell and Dr Natalia develop highfor throughput, highly and disrupting using a novel zebrafish model of diabetes, diagnostic strategies treatment to 2010 demonstrate inmessages C. sensitive eleganstohow abnormalities, hydrocephalus, as well is asArtemenko Health Research Board of Ireland, Arl13b atinciliary membrane meeting UCDand Conway Instituteoptions in October This research was partially supported by programme. the neurons that send visual our Reference: who developed GlycoExtractor robust strategies that detail the glycome of The UCD Conway team, including postdoctoral which resembles the early stages the of diabetic prevent CKD development. Email “Our results suggest that a molecular highlighted among top ten percent brain.

Predominant cone photoreceptor dysfunction in a researchers Dr.humans.

Craig Slattery Dr. Natalia retinopathy in It is anand exciting Syskid (www.SysKid.eu) was established to tara.mcmorrow@ucd.ie for details of a PhD hyperglycaemic model of non-proliferative diabetic development for the who now hope to Until now, was unclear if of thechronic changes to Martin, will utilise cellgroup culture and animal position currently available. further ouritunderstanding kidney retinopathy.

Yolanda Alvarez, Jenneth Chen, Alison extend theirinresearch a non vessels and neurons occurredbyindependently of led further Meta-analysis UCD researchers by HIV nef are critical in determining the rate studies humans and haveestablish shown that Reynolds, of Nore Waghorne, John J. O’Connor, Breandan model stage diabetic disease. with gross one other and which of retinal neuron is Shields Kennedy. Disease Models & Mechanisms (2010) Denis Conwaytype Fellow, Professor Denis has of late of disease progression.

Professor progression was associated determined that there is no clear evidence Shields believes that searches for modifiers of deletions in the nef gene. that particular defective viral sequences in progression rates should now focus on other larger programmes such as the new MSc in We introduced advanced I amHIV-1 delighted to welcome you to the the However, much 4 ofnew the research in core the area to nef gene or certain host and viralresearch, factors. “Systematic Commenting on the Dr Kennedyevaluation likely to die as a result of the raised New research the led by Conway Fellow Dr regions ofmost date has been based on case technology modules onobservational a pilot basis or this Conway Focus and look role forward to working Imaging commencing in by September 2010. protein play a significant in disease ofestablishing large quantities of data bioinformatics glucose levels seen in diabetes.

Breandán Kennedy indicates that treatment said, “By a robust model for early studies rather than rigorous, systematic academic year; those covering principles progression. can be just as important inblock refuting cells, tissues and fluids.

EUROCarbDB, a research infrastructure design Glycomics the supporting framework tract is diabetic lined with cells the contents results in both academic outputs and the into Irish biopharmaceutical with you in thelook coming months! of diabetic needs blindness should at development stage retinopathy, we would Welcome! innovation agenda and translation 2010 draws to athat close, I would scientific evaluation. work by doctoral and lateAs Dr Kennedyapplication andpractical his team foundThis that newclinical blood hypotheses are current in initiatives, the literature, as study funded the EU 6th Framework of extensive, databases and of the by gut from leaking into the intestine. of research toward product company, Sigmoid Pharma recently scooped and aspects of imaging and applied protecting thewell-curated neurons responsible for colour Ibetter hope that athat number of new hope to understand the progression of In an HIV-infected patients can be categorisedCommercial on candidate Ravindra Pushker set out to clinical application. like to take the opportunity to packages that support HPLC anddevelopment the neuronalwith cellindigenous death in diabetic it ispatient, in discovering unknown patterns”, Programme.

Prospective users access flexible tools.

Currently, this field IBD this barrier iscan broken and the thehe said. companies.” the and overall Innovation of the Year awardvessels at vision inanalytical the eye not just targeting the proteomics began in late March and willset run the disease and pave the way for identifying the basis of the number of years it takes for determine in a substantially larger sample As an institute with an increasingly including the early-stage researcher forum instruments cannot facilitate the extraction of issue ofIrish Conway Focus comesretinopathy as can arise independently of each congratulate Conway on of study lacks This the established, GlycoExtractor tool on gut contents offor the leak outresearchers into surrounding the inaugural Times All-Island blood vessels as is currently practice. new targets its successful treatment”. until mid-June a that further twodisease modules in drug them to progressthe to AIDS. Some patients if anyof association exists between This research was funded through Science large data.identified In with an effort to alleviate Commenting on the Taylor collaboration, Dr http://glycobase.nibrt.ie:8080/DemoGlycoExtra other.quantities In addition, they cone interdisciplinary research focus andSME, described in this issue, will not only comprehensive and centralised data areas.

The research team in UCD Conway used Innovation Awards.

The life-science the TCD-UCD Innovation Academy As we define the research roadmap their achievements in the past twelve maintain stable CD4 lymphocyte counts and progression and particular amino acid Foundation Ireland and University College this bottleneck within high-throughput Coulter said, “The collaboration theplace Taylor genomics and flow cytometry taking photoreceptor neurons, those involved in with Nearly 2.5 million people worldwide are blind graduate, ctor/mainPage. collections, standards and information astrengthen model of funded IBD and, by applying a new class of founded by UCD pharmacology Dr The research was through Science expertise in specialist technology platforms, the community of Conway opens its doors to the first cohort that will maximise the value of Conway do not go on to develop AIDS even after more differences or deletions within the nef gene.

Dublin. months; a tiny fraction of which are glycomic projects, theclearly NIBRT team are have laboratory demonstrates the andweek-long used in daylight, most due to diabetic retinopathy.

This secondary over periods during thepotential summer reporting protocols that exist within knownand as hydroxylase inhibitors, were Ivan Coulter, has actively collaborated colour with vision Foundation Ireland Health Research Referencedrugs we are placed to participatenew indeveloped the byathat than 10uniquely years of infection. researchers andthe forge interdisciplinary web-based tool that interfaces can be realised through PhD graduates to embrace research by tackling big focused questions in Board. highlighted andnew look to affected the glucose levels. complication diabetes activates the growth interface for highforward GlycoExtractor: genomics andofof proteomics. able toA web-based almost here, completely reverse the Conway Fellow, Professor Cormac aTaylor On ahigh per patient basis, there was no excess of months. with the Waters chromatography software application of basic research.

The development education and training of the next of new leaky blood vessels in the eye and is processing of HPLC-Glycan data throughput links but will celebrate and heighten culture ofareinnovation within graduate biology and biomedicine, fostering symptoms of the disease. since being granted Science Scientists curiousaas to whyFoundation these longLTNP patients with one or more defective nef the challenges of the coming year.

The research team made their observations Researchers, Drthe Natalia Artemenko and Dr package to of improve automate the export a smartand economy will depend on like-minded Natalia V. Artemenko, Matthew P. Campbell, and Pauline responsible for of Ireland industry research partnership term,death nonprogressor (LTNP) patients do not a novel when compared tothis progressors. generation of photoreceptors, research scientists.

Theaward newly awareness of our research and9 innovation education. initiative and that of asequences dynamic innovative culture will ifbe M. Rudd Journal using zebrafish model ofidentifying diabetes, of 2010, We hope determine from pilot Matthew Campbell from theThis National Institute of data to various filetoformats for subsequent “When weProteome appliedResearch, these new drugs(4), to pp our IBD collaborative partners opportunities the neurons that send visual messages to our Reference: Reference: in 2004. develop AIDS. This may reflect differences in While the high frequency of amino acid 2037–2041 launched PhD in Bioinformatics which resembles thefor early stages ofofdiabetic Professor Walter Kolch successes. the Dublin Academic Medical Centre integral to our success.

It will resonate of Bioprocessing Research & programme Training (NIBRT) analysis.

The modular architecture the tool model, the gut was tricked into it and realising basic andfrom applied research Meta-analysis to test the association ofthinking HIV-1 nefthat amino demand training within UCD as well brain.

Predominant cone photoreceptor dysfunction in a the host, viral genetics or environmental replacement at particular residues is indicative The Irish TimesBiology award recognises the stellar retinopathy in humans.

It is an exciting acid being differences and deletions with disease progression. led by Conwayand Fellow, Professor Pauline Rudd also the manipulation of datacentres from was of oxygen.

This activated synergies.

This collaboration, initiated through Director Systems recently attracted 80 facilitates (DAMC) opens new possibilities for throughout the scientific process; from hyperglycaemic modeldeprived of non-proliferative diabetic as from external academic and factors that could potentially be exploited for of rapid evolvement, permutation testing Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields. innovative performance of Sigmoid Pharma in development for research the group who now hope to the retinopathy.

Until now, it was unclear if the changes to other systems. have developed an open access, web-based protective pathways, which in Alison turn prevented a SFI supplement, highlights Yolanda Alvarez, Chen, Professor WalterJenneth Kolch EU 120 non-EU applicants forfor up the to 15 data management the and treatment of of the disease. showed residues with more replacements Journal of Virology, Apr 2010 p3644-3653 industry willto dictate of harnessing Conway’s research discovery translation in partnership their application research and of development. further extend their that research andstand-alone establish adelivery vessels and occurred independently Reynolds,the Nore Waghorne, O’Connor, Breandan interface thatneurons facilitates extraction, querying death of theJohn cellsJ.that line the potential that innovative indigenous companies than expected were not statistically significant.

The NIBRT these team are now working to integrate advanced modules inclusion within Director, UCD&Conway Institute studentships.

The company developed two drug model stage diabetic disease. one sharing other and type ofhas retinal neuronhave isin new with industry.

Kennedy. gastrointestinal Disease Models Mechanisms (2010)Professor and of which HPLC-glycan data generated tract,” explained working with academia can or realise.”

Studies in model organisms shown that of late GlycoExtractor with the EUROCarbDB technologies, and virus SmPill™, which high throughput processes.

Taylor. “Our pre-clinical trial data can now infection with LEDDS™ nef-deficient shows an not The researchers conclude that current data framework to provide a comprehensive high-Pharma has Taylor’s collaboration with Sigmoid only enhance the solubility andand permeability of inform the next phase Sigmoid Pharma product provides no evidence that individual residues attenuated course of infection some Glycosylation isthe the most and throughput certainly HPLC data analysis platform for metrics with been successful by these drug butcommon can deliver it to targeted locations development pipeline”. structurally diverse and annotation experimental co-authoredofpublications to date in two of in thepost-translational gastrointestinal tract, including thethe storagethree modification ofcolon. proteins. More than half of all data. The integration next generation In addition to the product that is currently in the highestofranking scientific journals in the

GlycoExtractor advances glycan data manipulation

Zebrafish model gives insights into diabetic blindness Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Director’s Message Zebrafish model gives insights into diabetic blindness Conway collaborator scoops Irish Times Innovation Award GlycoExtractor advances glycan data manipulation Director’s Message

UCD CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH

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Conway collaborator Times Innovation Award Mismanagement of cellularscoops waste Irish linked to Alzheimer’s

Conway collaborator scoops Irish Times Innovation Award Conway collaborator scoops research Irish Times Innovation Award 2010 Festival medal for signalling

Irish biopharmaceutical development company, Sigmoid Pharma recently scooped IrishMarc biopharmaceutical the overall Innovationreceived ofdevelopment the Year award at Dr Birtwistle the 2010 company, Sigmoid Pharma recently scooped the inaugural Irish Times All-Island UCD Conway Festival of Research & the overall Awards.

Innovation thesponsored Year award at Innovation Theoflife-science SME, Innovation gold medal, by the inaugural Irish Times All-Island founded

by UCD pharmacology graduate, Dr Roche, for his research to decipher Innovation Awards.

The life-science SME, Ivan Coulter, has actively collaborated the mechanism cells use tograduate, turn onwith founded Fellow,

by UCD Professor pharmacology Dr Conway Cormac Taylor and biological decisions.

As part of Ivan off Coulter, has actively collaborated with since being granted a Science Foundation this prize, MarcProfessor is selected as the UCD Conway Fellow, Cormac Taylor Ireland industry research partnership award representative forathe 2010Foundation Roche since being granted Science in 2004.

Researcher of the Yearpartnership competition.

Ireland industry research award The Irish Times award recognises the stellar in 2004. innovative performance of Sigmoid Pharma in A postdoctoral researcher in Systems The Irish Times award recognises the stellar their application ofDr research and was development.

Biology Ireland, Birtwistle innovative performance of Sigmoid Pharma in initially shortlisted from over 85 The hasofdeveloped twodevelopment. newConway drug theircompany application research and scientists to present his work at the technologies, LEDDS™ and SmPill™, The company has developed two new which drug not moderated sessions held during only enhanceposter the solubility permeability of technologies, LEDDS™ and and SmPill™, which not the 10th annual UCD Conway Festival the but can it toand targeted locations onlydrug enhance the deliver solubility permeability of of Research & Innovation on Thursday, in gastrointestinal tract, the 13:12 thethe drug but can deliver it07/05/2010 toincluding targeted locations May 2010.qxd:Layout 1 copy September 16th in the Institute. colon. in the gastrointestinal tract, including the colon.

The Sigmoid Pharma-Taylor He impressed the judgingcollaboration committee is with the description of hisof work facilitating thePharma-Taylor development a newthat is The Sigmoid collaboration uses a systems biology approach facilitating the development oftreatment a new toof therapeutic approach for the understand how cancer cells therapeutic approach for the treatment of inflammatory bowelbreast disease (IBD) by bringing listen tothe two different signals. inflammatory bowel disease (IBD)One by together research methodology ofbringing the signal causes these cells to grow,of the together the research Taylor group with the methodology proprietary whereas thewith other these cells to Taylor group thecauses proprietary liquid/emulsion drug delivery system, differentiate.

These signals activate or liquid/emulsion drug by delivery system, LEDDS®, developed Sigmoid Pharma. inactive potential, LEDDS®,subsequent developed bysignalling Sigmoid Pharma. which whenon perturbed faulty have Commenting the award,orProfessor Taylor Commenting theinaward, Professor been implicated theforprogression of his said, “We are on delighted Dr Coulter Taylor and said, “We are delighted for Dr Coulter and his numerous types cancer. team and indeed it of reflects well on our team and indeed it reflects well on our partnership. A key driver of successful partnership. A key driver of successful scientific research in 2010 is meaningful scientific research in 2010 is meaningful interaction with industry industry that that interaction of of academia academia with

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

The cells in our bodies continually listen application toward clinical product for signals of in research their local environment Commenting with on the Taylor collaboration, development indigenous companies.” and then make appropriate decisions Dr Coulter said,body “Thefunctionality. collaboration with the Taylor for proper A major Commenting on the Taylor collaboration, Dr laboratory clearly demonstrates the research potential challenge in current biomedical Coulter said, “The collaboration with the Taylor that can be realised through focused is to understand the languagethe ofpotential this laboratory clearly demonstrates applicationin ofterms basic research.

The development listening of the chemical that can be realised through focused of a smart occurring economy will depend like-minded reactions within theon cell. application basic research.

The opportunities development collaborative partners identifying Central to of this systems biology approach of a smart economy will depend on like-minded and realising basic andunderstanding applied researchinto is casting biological partners identifying opportunities acollaborative mathematical formalism initiated that allows synergies.

This collaboration, through and realising basic and applied research the of computers andhighlights maths tothe a SFIuse research supplement, synergies.

This collaboration, initiated through understand the system works. that how innovative indigenous companies apotential SFI research supplement, highlights the working with academia can realise.” potential that innovative indigenous companies Dr Viviana Marzaioli, Dr Sandra Malynn, working with academiawith canSigmoid realise.”Pharma has Taylor’s collaboration

Melissa Morine, Karen Harford, Lisa Shine certainly beenAhmed successful by these metrics and Tauseef received category Taylor’s collaboration with Sigmoid Pharmawith has three co-authored publications to date in two of prizes for delivering concise overviews certainly been successful by these metrics with Page 3 of work in the themedjournals moderated thetheir highest ranking scientific three co-authored publications to date in in the two of poster sessions. field,highest Gastroenterology and Proceeding the ranking scientific journals inof thethe National Academy of Sciences, as well as field, Gastroenterology and Proceeding of the

Conference heard keynote National Academy of Sciences, as well as the generation ofdelegates proprietary innovative products lectures from Professor Rosemary generation of proprietary innovative and the creation of high-skilled jobs.products O’Connor, University Collegejobs.

Cork on and the creation of high-skilled Morepotential than 15,000 people in Ireland and the of signalling regulators More than 15,000 in Ireland andwith the millions of therapeutics people people worldwide are living as cancer and Professor millions of people worldwide living with the Michael White, University oftherapeutic Liverpool, symptoms IBD today.

Currentare symptoms today.

Current therapeutic spoke biology approaches optionsabout for IBD thissystems chronic debilitating disease are options this debilitating disease are that arefor useful to study cell signalling. very limited withchronic surgery often being the only very often beingcurrently the only viablelimited option.with Thesurgery Sigmoid product, viable option.

The Aebersold, Sigmoid currently Professor Ruedi ETH Zurich, in a phase II clinical study, product, uniquely enables in a phase the II clinical study, uniquely enables delivered lecture of the oral delivery ofplenary a powerful drug without oral delivery of a powerful drug without causing systemic side-effects. causing systemic side-effects.

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

tract is lined with cells that block the contents of the gut from leaking into the intestine. In an tract is lined with cells that block the IBD patient, barrier ishow broken andcontents the Festival andthis described proteomic of the gutof from leaking intestine.

In an contents thecan gut generate leakinto out the into surrounding experiments complete, IBD patient, thisand barrier is in broken and areas.

The research team UCD Conway used reproducible quantitative datathesets contents ofideally the gut leak out surrounding areof suited tointo support athat model IBD and, by applying a newthe class of areas.

The research team in UCD Conwaywere used generation of models in drugs known asmathematical hydroxylase inhibitors, aable model ofbiology IBD completely and,research. by applying systems to almost reversea new the class of drugs known symptoms of as thehydroxylase disease. inhibitors, were able almost completely reverse the Theto10th annual UCD Conway Festival of “When we of applied these new to our IBD symptoms disease.

Research & the Innovation wasdrugs sponsored by model, the gut&was tricked into thinking that it BioSciences Roche.

“When we applied these new drugs to our IBD was being deprived of oxygen. This activated model, the gut was tricked into thinking that it protective pathways, which in turn prevented was being deprived of oxygen. This activated the death of the cellswhich that line the prevented protective pathways, in turn gastrointestinal explained the death of the tract,” cells that line theProfessor Taylor. “Our pre-clinical trial dataProfessor can now gastrointestinal tract,” explained inform “Our the next phase Sigmoid product Taylor. pre-clinical trial dataPharma can now development pipeline”. inform the next phase Sigmoid Pharma product development pipeline”.

In addition to the product that is currently in phase II clinical Pharma in is In addition to thestudies, productSigmoid that is currently developing a LEDDS™-enabled phase II clinical studies, Sigmoidformulation Pharma is of developing a LEDDS™-enabled formulation of the hydroxylase inhibitor the hydroxylase inhibitor(DMOG) to bring about dimethyloxaloylglycine dimethyloxaloylglycine (DMOG) to bring about effective, safe and targeted delivery of this effective, and targeted potential safe therapeutic agent.delivery of this potential therapeutic agent.

Prof. Walter Kolch, Director, UCD Conway; Simon Thorpe, Roche Diagnostics Ltd; Dr Marc Birtwistle, winner 2010 UCD Conway Festival gold medal; Dr Oliver Blacque, Chair, Conway Lecture & Seminar Series committee.

Conway collaborator age scoops Irish Times Innovation Award Science in the information Irish global biopharmaceutical development The scientific community In the company, Sigmoid recently scooped information age isPharma not only concerned the overall Innovation of thediscovery Year award with advancing scientific butat the inaugural Irish Times All-Island of with improving the methodology Innovation Awards.

The life-science SME, the scientific process.

There are two recent of Conway researchers foundedexamples

by UCD pharmacology graduate, Dr Ivan Coulter,this has actively collaborated with influencing led by Meta-analysis by work.

UCD researchers

results in bothproposal, academic outputs The MIAPAR which and the application of research toward was outlined earlier this yearclinical product development with indigenous companies.” in a communication to Nature Biotechnology, allows subsequent users Commenting on the Taylor collaboration, Dr to make a fully informed evaluation of Coulter said, “The collaboration with the Taylor the validity of conclusions drawn from laboratory clearly demonstrates the potential use of ainparticular product. studies humans have shown shown that that non non

since being granted a Science Foundation Conway postdoctoral Dr Niall determined that there isresearcher, no clear evidence Ireland industry research partnership award Haslam from the Complex Adaptive that particular particular defective viral sequences in that defective viral & sequences in in 2004.

Systems Laboratory (CASL) worked the HIV-1 nef gene or certain regions of the the HIV-1 nef gene or certain regions ofon the the minimum information about protein play significant role The Irishplay Times award recognises theprotein stellar protein aa significant role in in disease disease affinity reagent (MIAPAR) proposal; an in progression. innovative performance of Sigmoid Pharma progression. international to define a checklist their applicationeffort of research and development.

HIV-infected information patients can categorised on of the HIV-infected can be bedescribing categorised on Therequired companypatients has developed two new drug the basis of of theanumber ofbinding years it reagent takes for properties protein the basis of the numberand of years it takes for not technologies, LEDDS™ SmPill™, which them every to progress to AIDS. Some patients with known partner. only the solubility and permeability themenhance to progress to binding AIDS. Some patients of

application of basic research. The development Dr Niall Haslam that “by deletions the nefexplains gene.depend of a smartineconomy on like-minded providing MIAPAR will compliment collaborative partners identifying opportunities However, much of the research in documents for the affinity reagents However, much of the research in the the area area to to and realising basic and applied research date been observational used in experiments with theor date has has been based based on onalong observational or case case synergies.

This collaboration, initiated through studies than systematic scientific communication the research, studies rather rather than rigorous, rigorous,of systematic ascientific SFI research highlights the evaluation.

This work by scientists cansupplement, support the efficient use of scientific evaluation.

This work by doctoral doctoral potential that innovative indigenous companies candidate Ravindra Pushker set out to the products for the benefit of the entire candidate Ravindra Pushker set out to working with can realise.” determine in academia a substantially larger sample set scientific determinecommunity.” in a substantially larger sample set

tract lined with cellsinthat block the contents tasksis encountered a typical protein of the gut fromproject leaking while into the intestine. In an engineering integrating IBD this barrier broken and the datapatient, deposition in theis process. contents of the gut leak out into surrounding areas.

The research teambenefits in UCD Conway Commenting on the of PEAT,used aDr model of IBD and,“PEAT by applying a new class Nielsen said, incentivises dataof drugs ascritical hydroxylase were storage byare integrating theinhibitors, processthe with of nef in rate of HIV HIVknown nef are critical in determining determining the rate able to almost completely reverseapplication. the the analysis tools in a single of progression.

Professor Denis of disease disease progression.

Professor Denis symptoms of the that disease.

Through widespread use of for PEAT, we canof Shields Shields believes believes that searches searches for modifiers modifiers of

Bioinformatic analysis of HIV progression studies Conway Fellow, Fellow, Professor Professor Cormac Taylor has Denis Shields Conway

maintain stable CD4 lymphocyte counts and the drug but canCD4 deliver it to targeted locations maintain stable lymphocyte counts and do not go on to develop AIDS even after more Currently, there are tract, multiple sources in the gastrointestinal including the more do not go on to develop AIDS even after than 10 years of on infection. of information affinity reagents colon. than 10 years of infection. in existence including commercial Scientists are curious as to why these longThe Sigmoid Pharma-Taylor collaboration is catalogues, experimental results Scientists curious as to why these longterm, non-are progressor (LTNP) patients not facilitating the development of patients a new published in scientific journals and do term, nonprogressor (LTNP) do develop AIDS. This may reflect differencesnot in web portals that centralise affinity therapeutic approach for the treatment of develop This mayorreflect differences in the host,AIDS. viral genetics environmental reagent properties from many sources. inflammatory bowel disease (IBD) by bringing the host,that viral genetics or environmental factors could potentially be exploited for However, available information together thethe research methodology of the factors that could potentially be exploited for the treatment of the disease. may incomplete, inaccessible, Taylorbe group with the proprietary the treatment of the disease. unsubstantiated ordelivery may even appear liquid/emulsion system, Studies in modeldrug organisms have shown that contradictory due to of precision in LEDDS®, developed by lack Sigmoid Pharma. infectioninwith nef-deficient virus shows Studies model organisms have shownanthat target orwith sample descriptions. attenuated course of infection and somean infection nef-deficient virus shows Commenting on the award, Professor Taylor 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

that can be realised through focused progression was associated with with gross gross

if any association exists Taylor’s collaboration withbetween Sigmoiddisease Pharma has if any association exists between disease

progression and particular amino acid Conway Fellow, Dr JensbyErik Nielsen certainly been successful these metrics with progression and particular amino acid differences or deletions withinato the nef in gene. and his team have created protein three co-authored publications date two of differences or deletions within the nef gene. engineering analysis tool (PEAT) that the highest ranking scientific journals in the of On a per patient basis, there was no excess facilitates the analysis ofProceeding experimental On a Gastroenterology per patient basis, there wasdefective no excess field, and of the LTNP patients with or more nefof data generated inofone the course a as the LTNP patients with one or more defective nef National Academy Sciences, asof well sequencesproject when compared toensuring progressors. research as well as that generation of proprietary innovative products sequences when compared to progressors.

While the high frequency of amino acid this valuable data is available foracid future and the creation of high-skilled jobs.

While the high of amino replacement at frequency particular residues is the indicative use.

The team recently described replacement at particular residues is indicative of rapid evolvement, permutation testing application in thepeople journal, Nucleic More than 15,000 in Ireland andAcids of rapid evolvement, permutation testing showed that residues with more replacements Research. millions of people worldwide are living with the

showed that residues with more replacements than expected were statistically significant. symptoms IBD today.not Current therapeutic than expected were not statisticallydisease significant. options for this chronic debilitating PEAT is not simply a laboratory The researchers conclude that current data are very limited with surgery often being the only information management system, but provides no evidence that individual residues The researchers conclude that current data has been designed to address specific 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.

create and share high quality datasets progression rates should now focus progression ratesthese should now focus on other “When we applied new drugs toon ourother IBD on the connections between protein host and viral factors.

“Systematic evaluation host and factors.

“Systematic evaluation model, the viral gut was tricked into thinking that it sequence, structure andbyfunction”. of large quantities of data bioinformatics of large by bioinformatics was beingquantities deprived of data oxygen.

This activated can as in can be be just just as important important ininrefuting refuting protective pathways, which turn prevented The work on MIAPAR wasinsupported hypotheses that are the the death of the that lineinthe hypotheses thatcells are current current the literature, literature, as as through funding received from European itit is in discovering unknown patterns”, he said. gastrointestinal tract,” explained Professor is in discovering unknown patterns”, Union Framework Programmes (EU he FP)said.

Taylor.

“Our pre-clinical trialthrough data can now funded Science 6This & 7.research PEAT iswas being funded through This research was funded through Science inform the next phase Sigmoid Pharma product Foundation Ireland and University College awards from Science Ireland, Foundation Ireland and Foundation University College development pipeline”.

Dublin. the Health Research Board, Higher Dublin.

Education and UCD Ad Astra In addition toAuthority the product thata is currently in scholarship. is available at http:// phase II clinicalPEAT studies, Sigmoid Pharma is enzyme.ucd.ie/PEAT developing a LEDDS™-enabled formulation of the hydroxylase inhibitor Reference: Reference : Reference: to test the association Meta-analysis ofto HIV-1 nef amino dimethyloxaloylglycine (DMOG) bring Bourbeillon J et al.Minimum information aboutabout acid differences with disease progression.

Meta-analysis testdeletions the association of HIV-1 nef amino effective, safetoand and targeted delivery of this aRavindra protein Pushker, affinity reagent (MIAPAR).

Nature Jean-Marc Denisprogression.

C. Shields. acid differences and deletionsJacquē, with disease Biotechnology 2010 Jul;28(7):650-3. potential therapeutic agent.

Journal Virology,Jean-Marc Apr 2010 p3644-3653 RavindraofPushker, Jacquē, Denis C. Shields.

Journal of Virology, Apr 2010 p3644-3653

Farrell D et al. Capturing, sharing and analysing biophysical data from protein engineering and protein characterization studies Nucl. Acids Res. (2010) 38(20): e186 doi:10.1093/nar/gkq726

UCD Conway researchers believe that Irish biopharmaceutical development acompany, failure to maintain an efficient flux of Sigmoid Pharma recently scooped cellular waste through lysosomes the overall Innovation of the Year awardisata risk factor for developing Alzheimer’s the inaugural Irish Times All-Island disease. findings of their research InnovationThe Awards.

The life-science SME, were recently in the Journal founded

by UCD published pharmacology graduate, Dr of Biological Chemistry.

Ivan Coulter, has actively collaborated with

neuron and may underlie the results infunction both academic outputs and the cognitive associated with Alzheimer’s applicationloss of research toward clinical product disease. development with indigenous companies.”

Commenting Taylor Research collaboration, Dr a study ledonbytheHealth BoardSuccess in EU FP7 call Infunded Coulter said, “The fellow, collaboration with Boland, the Taylor research Dr. Barry laboratory demonstrates the potential the clearly co-supervision of Conway Success in EU FP7 call under that can Prof. be realised through focused Fellow, Dominic Walsh and Prof.

Conway Fellow, Professor Cormac Taylor

disease (CKD) and improve treatment, Conway researchers

by Dr.cells Tara strikes application of basic research.

The development Frances Platt (University ofpatient Oxford), AVs The statealed of living sincemetabolic being granted Science Foundation of a smart economy will depend on like-minded McMorrow and Professor Michael Ryan have with particular focus on CKD arising from were shown to accumulate inside neurons aIreland fine balance between growth and industry research partnership award disease (CKD) and cannot improve patient treatment, Conway researchers led

by Dr.this Tara collaborative identifying opportunities diabetes and partners hypertension.

The multiwhen lysosomes digest AVs and successfully secured €485,500 inequilibrium funding as degradation.

Cells maintain in 2004. and realising basic applied McMorrow and making Professor Michael Ryan have with particular focus on CKD arising when AVs are not and delivered toresearch lysosomes. disciplinary research consortium hasfrom 25 partconstantly of an overall awardnew, to the Systems by and removing The Irish Times award recognises the stellar synergies.

This collaboration, initiated through diabetes hypertension. multi-partners) successfully €485,500 in fundingtheir as old, parts ofsecured themselves.

TheyKidney package partnersand (16 universities, 9The industry Biology towards Novel Chronic innovative performance of Sigmoid Pharma in a SFIteam research supplement, highlights the disciplinary research consortium has 25 part ofwaste anDiagnosis overall award tothat the Systems own into vesicles are degraded The used this model to investigate from 15 countries and the project is due to run Disease and Treatment (SysKid) their application of research and development. potential(16 that innovative indigenous partners universities, 9 industry partners) Biology towards Novel ChronicasKidney by acidic organelles lysosomes. whether a protein associated withcompanies plaque for five years. consortium theknown European Union FP7 The companyunder has developed two new drug working with academia canproject realise.”

This process cellular rubbish disposal from 15 countries and the is due to run formation disease, amyloid Disease Diagnosis and Treatment (SysKid) May 2010.qxd:Layout 1of copy 07/05/2010 Page 3 in Alzheimer’s programme. technologies, LEDDS™ and SmPill™, which 13:12 not involves cells eating parts of themselves precursor proteinteam, (APP), is delivered Thefive UCD Conway postdoctoral for years. consortium under the European Union FP7 Taylor’s collaboration withincluding Sigmoid Pharma has only enhance the solubility and permeability of and is known as autophagy (self-eating). to lysosomes byCraig AVs.Slattery They found programme. researchers Dr.successful and metrics Dr.that Natalia Syskid established to certainly by these with the drug(www.SysKid.eu) but can deliver itwas targeted locations The UCD been Conway including postdoctoral During autophagy, wasteto material is fragments APPteam, areculture degraded by Martin, willof utilise cell and animal further our understanding of chronic kidney three co-authored publications to date in two in the gastrointestinal tract, including the researchers Dr. Slattery and Natalia of Syskid (www.SysKid.eu) was established to digested into basic building blocks (sugars, lysosomes butCraig notscientific delivered toDr. lysosomes the highest rankingcell journals in the colon. our Martin, will utilise culture and indicated animal further understanding of chronic kidney amino acids and lipids) that can then be by AVs. Instead, their research field, Gastroenterology and Proceeding of the reused to make new parts of the cell. that amyloidogenic APP fragments are The Sigmoid Pharma-Taylor collaboration is National Academy of Sciences, as well as the Neurons for manyofdecades delivered to lysosomes from the plasma facilitatingsurvive the development a new in generation of proprietary innovative products the humanapproach brain andforhave exceptionally membrane via endocytosis. therapeutic the treatment of and the creation of high-skilled jobs. efficient autophagy.

However, inflammatory bowel disease (IBD)in bybrains bringing of people affected by Alzheimer’s disease, Commenting on the study, Dr. Boland More than 15,000 people in Ireland and together the research methodology of the the ability ofwith neurons to clear out cellular said, highlights the important role the cells,“This tissues and fluids.

Glycomics needs the proprietary supporting framework millions of people worldwide are living with Taylor group the waste is compromised.

This leads toand an that lysosomes play in removing cellular of extensive, well-curated databases symptoms IBD today.

Current therapeutic cells, tissues and fluids.

Glycomics needs the delivery supporting framework liquid/emulsion drug system, Commercial neurons, packages that support HPLC accumulation of waste containing vesicles waste clarifying theare flexible analytical tools.

Currently, this optionsfrom for this chronicwhile debilitating disease of extensive, well-curated databases andfield LEDDS®, developed

by Sigmoid Pharma. instruments cannot facilitate the extraction of Commercial packages that support HPLC or autophagic vacuoles (AVs) thatthis impair route APP fragments take on their delivery very limited with surgery often being the only of study lacks the established, flexible analytical tools.

Currently, field

to lysosomes.

We believe that the therapies tract is lined with cells that block contents aimed at from improving waste In an of the gut leakinglysosomal into the intestine. disposal could alleviate IBD patient, this prevent barrier isand broken and thethe neuronalofdysfunction associated with contents the gut leak out into surrounding Alzheimer’s disease.” areas.

The research team in UCD Conway used a model of IBD and, by applying a new class of This work was grants from drugs known as supported hydroxylaseby inhibitors, were the Health Research Board of Ireland, able to almost completely reverse the models to identify processes involved in early the Wellcome Science Foundation symptoms of theTrust, disease.

CKD progression investigate Ireland and UCDand Seed Fund. novel models to identify processes “When we applied these new drugs toinour IBD strategies for preventing andinvolved slowing theearly Reference CKD progression andtricked investigate novel model, gutof was into thinking that it progression the disease.

These studies will Boland B,the Smith DA, Mooney D, Jung SS, Walsh DM, Platt strategies for preventing slowing the in was beingMacroautophagy deprived of oxygen.

This activated be(2010) integrated with clinical epidemiological FM isand notand directly involved progression ofofthe These studies will protective pathways, which in turn prevented the metabolism amyloid precursor protein.

Journal of studies across thedisease. consortium using systems Biological 285:37415-37426. be integrated withcells clinical epidemiological the deathChemistry of the thatinand line theto develop new biology methodologies order studies across the consortium using systemsto gastrointestinal tract,” explained Professor diagnostic strategies and treatment options biology methodologies in order to develop Taylor.

“Our pre-clinical trial data can now new prevent CKD development. Email diagnostic treatment options inform the strategies next phaseand Sigmoid Pharma tara.mcmorrow@ucd.ie for details of a product PhDto prevent CKD development.

Email development pipeline”. position currently available. tara.mcmorrow@ucd.ie for details of a PhD In addition to the product position currently available.that is currently in phase II clinical studies, Sigmoid Pharma is developing a LEDDS™-enabled formulation of the hydroxylase inhibitor dimethyloxaloylglycine (DMOG) to bring about effective, safe and targeted delivery of this potential therapeutic agent.

EUROCarbDB, a research infrastructure design study funded abyresearch the EU 6th Frameworkdesign EUROCarbDB, infrastructure Programme.

Prospective users can access the study funded by the EU 6th Framework Cortical neuron showing the co-localisation of autophagic GlycoExtractor toolwith onlysosomes Programme.

Prospective users can access vacuoles (LC3, green) (LAMP1, red)the http://glycobase.nibrt.ie:8080/DemoGlycoExtra GlycoExtractor tool on http://glycobase.nibrt.ie:8080/DemoGlycoExtra ctor/mainPage. ctor/mainPage.

Reference

GlycoExtractor advances glycan data manipulation GlycoExtractor advances glycan data manipulation

large quantities data.

In product, antheeffort to alleviate instruments facilitate extraction of Commenting the award, Professor viable option.cannot TheofSigmoid currently comprehensive centralised data Taylor of study lackson theand established, this bottleneck within high-throughput large quantities of data.

In an effort to alleviate said, “We are delighted for Dr Coulter and his in a phase II clinical study, uniquely enables comprehensive and centralised data collections, standards and information this bottleneck team and indeed it reflects well on our glycomic projects, thehigh-throughput NIBRT have oral delivery ofwithin a powerful drugteam without collections, standards and information reporting protocols that exist within glycomic projects, the NIBRT teaminterfaces have partnership.

A key driver of successful developed a web-based tool that causing systemic side-effects. reporting protocols that exist within genomics and proteomics. developed a web-based tool that interfaces scientific research in 2010 is meaningful with the Waters chromatography software genomics and proteomics.

Under conditions, the gastrointestinal thenormal Waters chromatography software interaction of 1 academia industry that package to improve and automate the export Researchers, Dr Natalia with Artemenko and Dr 13:12 with May 2010.qxd:Layout copy 07/05/2010 Page 3 results intoboth academic outputs and the IrishElton biopharmaceutical development Dr. Rexhepaj received theand European (IHC) annotation andautomate facilitate the Researchers, Dr Natalia Dr package improve and export of data to various file formats for the subsequent Matthew Campbell fromArtemenko the National Institute application ofof research toward clinical product company, Pharma recentlyInstitute scooped Society ofSigmoid Toxicologic Pathology (ESTP) translation biomarker discovery to Matthew Campbell from the National of data to various file formats for subsequent of Bioprocessing Research & Training (NIBRT) analysis.

The modular architecture of the tool development with indigenous companies.” the overall Innovation of the Year award at thesis award in Budapest, Hungary on clinical implementation. of Bioprocessing Research & Training (NIBRT) analysis.

The modular architecture of the tool led by ConwayIrish Fellow, Professor Pauline Rudd also facilitates the manipulation of data from theby inaugural Times All-Island led Conway30th Fellow, Professor Pauline Rudd also facilitates thethe manipulation of data from September 2010.

This prestigious Commenting on Taylor collaboration, Dr have developed an open access, web-based other data management systems.

Innovation Awards. life-science SME, have developed an open access, web-based other data management systems.with prize, sponsored byThe Boehringer Ingelheim Dr. Elton Rexhepaj, together withthe Conway Coulter said, “The collaboration Taylor interface thatUCD facilitates extraction, querying founded by pharmacology graduate, Dr interface that facilitates querying The NIBRT team are now working to integrate Pharma GmbH & Co.extraction, KG, data is offered every Fellow, Professor William Gallagher and laboratory clearly demonstrates the and sharing of HPLC-glycan generated in The NIBRT team are now working topotential integrate Ivansharing Coulter, actively collaborated with and of has HPLC-glycan data generated in GlycoExtractor withthrough the EUROCarbDB that can be realised focused second year for a thesis in toxicological clinician-scientist, Dr. Donal Brennan high throughput processes.

GlycoExtractor with the EUROCarbDB Conway Fellow,processes.

Professor Cormac Taylor high throughput framework to basic provide aa comprehensive highapplication of Theproprietary development pathology. created IHC-MARK; novel, framework to provideresearch. a comprehensive highsince being granted a Science Foundation Glycosylation is the most commonand and throughput HPLCtoolkit data analysis platform for Meta-analysis by UCD researchers led by studies in humans have shown that nonfor of a smart economy will depend on like-minded image analysis for the assessment Glycosylation is the most common throughput HPLC data analysis platform Ireland industry research partnership award Conway Fellow, Professor Denis Shieldsanhas progression was associated gross theIHC-based storageand and annotation experimental structurally diverse post-translational collaborative partners identifying opportunities Rexhepaj’s doctoral thesis describes of markers.

This technology, structurally post-translational the storage annotation ofofwith experimental in 2004. diverse determined of that there isMore no clear deletions in the nefand gene. data.realising TheIHC-MARK, integration next generation modification ofimage proteins.

More thanevidence halfofofall all and basic applied research modification proteins. than half data.

The integration ofofisnext generation automated, analysis approach termed currently in The Times award recognises that Irish particular defective viral in synergies.

This collaboration, initiated through gene products have been shown tothe bestellar bioinformatic tools will further the treatment, disease (CKD) and improve patient Conway researchers led shown by Dr.sequences Tara bioinformatic tools will further the gene products have been to be for clinical pathologists and biomedical beta-testing phase and provides non-to However, much of the research in thea area innovative performance of Sigmoid Pharma in the HIV-1 nef gene or certain regions of the a SFI research supplement, highlights the glycosylated.

With manyspecific specific glycans or development of unified approaches for McMorrow and Professor Michael Ryan have with particular focus on CKD arising from glycosylated.

With many glycans or development of unified approaches for date has been based on observational or case researchers in histopathology laboratories supervised approach to the discrimination their application of research and development. protein playshowing a significant roleas incancer disease potential that innovative indigenous companies glycoforms showing potential as handlingrather large scalerigorous, glycomics datainitiatives initiatives glycoforms potential handling large scale glycomics data diabetes and hypertension.

Thesystematic multisuccessfully €485,500 in funding studies than to automate immunohistochemistry of biomarker protein expression at the The companysecured has developed twocancer new drug as progression. working with academia can realise.” biomarkers, there is an increasing need to with applications in biomarker discovery biomarkers, there isaward an increasing needwhich to not with applications in biomarker disciplinary research consortium has 25 part of an overall to the Systems scientific evaluation.

This workdiscovery by doctoral technologies, LEDDS™ and SmPill™, develop highthroughput, throughput, highly sensitiveon and develop high highly sensitive and partners (16 universities, industry partners) Biology towards Chronic Kidney HIV-infected patients can be categorised candidate Ravindra Pushker set outPharma toby Taylor’s collaboration with9 Sigmoid only enhance theNovel solubility and permeability of This research was partially supported by has This research was partially supported robust strategies that detail the glycome robust strategies that detail the glycome ofof from 15 countries and the by project due to set run Disease Diagnosis and Treatment the drug basis of the it (SysKid) takes for determine in asuccessful substantially larger sample certainly been theseismetrics with the but cannumber deliver itoftoyears targeted locations them progress Some patients if any association exists between disease for fiveco-authored years. consortium under to theAIDS. European Union FP7 three publications to date in two of in the to gastrointestinal tract, including the maintain stable CD4 lymphocyte counts and progression and particular acidin the programme. the highest ranking scientificamino journals colon.

More than 500 DNA samples from conditions.

It academic is frequently accompanied results both outputs and the Irish biopharmaceutical development The UCDinConway team, including do not go on to develop AIDS even after more differences or deletions within thepostdoctoral nef gene. field, Gastroenterology and Proceeding of the well characterised patients withscooped by psoriasisof vulgaris (PsV), aclinical common application research towardand product company, Sigmoid Pharma recently researchers Dr. Craig Slattery Syskid wascollaboration established tois The Pharma-Taylor thanSigmoid 10(www.SysKid.eu) years ofpsoriatic infection.

National Academy of Sciences, as Dr. wellNatalia as the psoriasis and arthritis in St chronic inflammatory disease that development with indigenous companies.” the overall Innovation of the Year award at On a per patient basis, there was no excess of Martin, will of utilise cell culture and animal further our the understanding of of chronic facilitating development a new kidney generation proprietary innovative products Vincent’s University (SVUH) affects the skin and mediated by T nef the inaugural Irish Times All-Island Scientists are curious as Hospital to why these longLTNP patients with oneis or more defective therapeutic approach for the treatment of and the creation of high-skilled jobs.

Commenting on the Taylor collaboration, Dr were analysed as The part of(IBD) two separate cells.

Innovation Awards. life-science SME, term, nonprogressor (LTNP) patients do not sequences when compared to progressors. inflammatory bowel disease by bringing Coulter said, “The collaboration with the Taylor genome-wide association studies most likely to die as a result of the raised New research led by Conway Fellow Dr founded by UCD pharmacology graduate, Dr develop AIDS. This may reflect differences in While the high frequency of amino acid More than 15,000 people in Ireland and together the research methodology of Dr the most likelyclearly to die demonstrates as a result of the New research led by Conway Fellow laboratory the raised potential (GWAS).

The results both studies glucose inindiabetes.

Breandán Kennedy indicates that treatment A stronglevels genetic component hadthe Ivan Coulter, has actively collaborated with the host, viral genetics orof environmental replacement atseen particular residues isPsA indicative millions of people worldwide arefor living with Taylor group with the proprietary glucose levels seen diabetes.

Breandán Kennedy indicates that treatment that can be realised through focused were recently published in Nature previously been suggested by several of diabetic blindness shouldCormac look atTaylorfor Conway Fellow, Professor factors that could potentially be exploited of rapid evolvement, permutation testing symptoms IBD today.

Current therapeutic liquid/emulsion drug delivery system, of diabetic blindness should look at Dr Kennedy and hisnow teamthere found that new blood application of basic The development Genetics. studies but until was limited protecting the neurons responsible for colour since being granted a Science the treatment the disease. showed thatthis residues with more replacements Dr Kennedy and hisresearch. team found that new blood options for chronic debilitating disease are LEDDS®, developed by SigmoidFoundation Pharma. protecting theofneurons responsible for colour vessels andeconomy the neuronal cell components death diabetic of a smart will depend on in like-minded knowledge of the genetic vision the eye research and not just targetingaward the Irelandinindustry partnership than expected were not statistically significant. vessels and the neuronal cell death in diabetic very limited with surgery often being the only Glycomics needs the supporting framework cells, tissues and fluids. vision in the eye and not just targeting the retinopathy independently of each collaborativecan partners identifying opportunities Studies in contribution model organisms have shown that The Irish to Professor these Commenting on award, Taylor contributing toarise PsA. Theproduct, findings blood vessels as the is currently the practice. in 2004. viable option.can The Sigmoid currently retinopathy arise independently of each of extensive, and blood vessels as is currently practice. other.

In addition, they that cone and basic andidentified applied research infection with nef-deficient virus shows an The realising researchers conclude that identified current dataa international collaborative projects was said, “We arewell-curated delighted for databases Dr the Coulter and his outlined in this publication Commercial packages that support HPLC in a phase II clinical study, uniquely enables other.

In addition, they identified that cone The Irish Times award recognises the stellar flexible analytical tools.

Currently, this field photoreceptor neurons, those involved in 6 Nearly 2.5 million people worldwide are blind synergies.

This collaboration, initiated through provides no evidence that individual residues attenuated course of infection and some coordinated by clinician scientists in the team and indeed it reflects well on our new genetic variant on chromosome instruments cannot facilitate the extraction oral delivery of a powerful drug without neurons, involved in of Nearly 2.5 million peopleofworldwide are blindin innovative performance Sigmoid Pharma of study lacks colour visionfor and inthose daylight, are most due to diabetic retinopathy. secondary aphotoreceptor SFI codes research supplement, highlights the SVUH Education & Research Centre; Dr. partnership.

Athe keyestablished, driver ofThis successful that aused protein, known asalleviate Actlarge quantities of data.

In an effort to causing systemic side-effects. colour vision and used in daylight, are most due to diabetic retinopathy.

This secondary their application of research and development. comprehensive and centralised data affected by high glucose complication of diabetes activates growth potential that innovative indigenous Brian Kirby (dermatology) andthe Conway scientific research in 2010 is meaningful 1, which isthe thought to playlevels. a key companies role in this bottleneck within high-throughput The company developed two new drug affected by the high glucose levels. complication ofhas diabetes activates theand growth collections, and information of new leaky blood vessels in the eye working with academia canthe realise.”

Under normal conditions, gastrointestinal Fellow, Professor Oliver FitzGerald interaction ofstandards academia with industry thatis both humoral and cellular immunity. glycomic projects, the NIBRT team have The research team made their observations technologies, LEDDS™ and SmPill™, which of new leaky vessels in the eye and is not reporting protocols that exist within responsible forblood the death ofstudies photoreceptors, (rheumatology).

Both have The research team made their developed a web-based tool that interfaces using a novel zebrafish model ofobservations diabetes, Taylor’s collaboration with Sigmoid Pharma has onlyneurons enhance the solubility permeability responsible for the death ofand photoreceptors, genomics and proteomics. the that send visual messages to ourof confirmed known genetic associations The genetic variant identified may result with the Waters chromatography software using a novel zebrafish model of diabetes, which resembles the early stages of diabetic certainly been successful by these metrics with the drug but can deliver it to targeted locations the neurons that associations send visual messages to our brain. but additional have also in upregulation of the IL-17 pathway, a of package to improve and automate the export Researchers, Dr Natalia Artemenko and Dr which resembles the early stages of diabetic retinopathy in humans.

It is an exciting three co-authored publications to date in two in the identified. gastrointestinal tract, including the brain. been key pro-inflammatory which Matthew from the National Institute of data to various filescientific formats fornow subsequent retinopathy inforhumans.

Itcytokine, iswho an exciting development the group hope to Until now,Campbell it was unclear if the changes to the highest ranking journals in the colon. may be critical in explaining of Bioprocessing Training (NIBRT) analysis.

The modular architecture of some the further extend their andwhy establish ato vessels anditneurons occurred independently field, Gastroenterology and Proceeding oftool the development for theresearch group who now hope Until now, was Research unclear if&the changes to of Psoriatic arthritis (PsA) is an people with psoriasis develop arthritis.

Theby Sigmoid Pharma-Taylor collaboration is also facilitates the manipulation of establish data as from led Conway Fellow,type Professor Pauline Rudd model ofextend late stage disease. one other andneurons which of retinal neuron is of National Academy ofdiabetic Sciences, as well the further their research and a vessels and occurred independently inflammatory joint disease that is This important observation opens up facilitating the which development of a web-based newneuron is other data management systems. have developed an open access, generation of proprietary innovative products model of late stage diabetic disease. one other and type of retinal distinct from other for chronic arthritic new avenues andjobs. potential therapeutic approach the treatment of interface that facilitates extraction, querying and the creationofofresearch high-skilled The NIBRT team arehave now shown working to non integrate inflammatory disease (IBD)generated byled bringing Meta-analysis

by UCD researchers by in studies in humans that and sharing of bowel HPLC-glycan data GlycoExtractor with the EUROCarbDB More than 15,000 people in Ireland and together the research methodology of the has Conway Fellow, Professor Denis Shields progression was associated with gross high throughput processes. framework provide a comprehensive high-the millions of to people worldwide are living with Taylor group with the proprietary

collaborator scoops Irish Timesvalidation Innovationresearch Award Conway Conway researcher recognised for biomarker GlycoExtractor: A web-based interface for high Reference of HPLC-Glycan throughput processing GlycoExtractor: A web-based interface fordata high Natalia V. Artemenko, Matthew P. Campbell, processing of HPLC-Glycan data and Pauline throughput tract isV.lined with cells block the contents subcellular Thethat applicability of IHCNatalia Artemenko, Matthew P.Research, Campbell, and Pauline M. Rudd Journallevel. of Proteome 2010, 9 (4), pp of the into the intestine.

In pp an MARK infrom oncology has been demonstrated M. Ruddgut Journal ofleaking Proteome Research, 2010, 9 (4), 2037–2041 2037–2041 IBD patient, this barrier is broken and thetypes, across multiple marker and tumour

contents of the gut leak out into surrounding including breast, colorectal, bladder and areas.

The research team in UCD Conway used ovarian cancer. a model of IBD and, by applying a new class of drugs known as hydroxylase inhibitors, were Dr. to Rexhepaj is now employed

by UCD able almost completely reverse the spin-out of company OncoMark Limited symptoms the disease. of HIV nef critical in determining the the rate where he are hopes to further progress of disease progression.

Professor Denis “When we applied these new drugs to our IBD commercialisation aspects of IHC-MARK Shieldsthe believes that searches modifiers model, gut was tricked into for thinking that itof and complementary image analysis progression ratesprocesses should now focusactivated on other was being deprived of oxygen.

This models to identify involved in early approaches in histopathology. hostprogression and viral factors.

“Systematic evaluation protective pathways, in turn prevented CKD and which investigate novel of large ofthat data byslowing bioinformatics the deathquantities of cells line the strategies forthe preventing and the can be just of as the important inThese refuting gastrointestinal tract,” explained Professor progression disease. studies will hypotheses that current inepidemiological the literature, Taylor.

“Our pre-clinical trial data can now NIBRT researchers Matthew Campbell and DrNatalia Nataliaas NIBRT researchers DrDrare Matthew Campbell and Dr be integrated with clinical and it is in the discovering unknown patterns”, he said.

Artemenko who developed GlycoExtractor inform next phase Sigmoid Pharma product Artemenko who developed GlycoExtractor studies across the consortium using systems development pipeline”. in order to develop new biology methodologies This research was funded through Science diagnostic strategies andUniversity treatment optionsinto Foundation Ireland and College In addition to the product that is currently for novel therapeutic strategies. tract is lined with cells that block the contents prevent development.

Email Dublin. phase IICKD clinical studies, Sigmoid Pharma is of the gut from leaking into the intestine.

In an tara.mcmorrow@ucd.ie for details of a PhD developing a LEDDS™-enabled formulation of IBD this barrier is broken and the Thepatient, second study investigated genetic position currently available. the hydroxylase inhibitor contents the increase gut leak out into surrounding variantsofthat susceptibility dimethyloxaloylglycine (DMOG) to bring about areas.

The research team in UCD Conwayatused to psoriasis and found associations effective, safe and targeted delivery of this Reference: onand, theunreported research, DrDr eight genomic aCommenting modelpreviously of IBD by applying aKennedy new class of Commenting research, Kennedy potential therapeutic Meta-analysis to on test the the agent. association of HIV-1 nef amino loci.

Seven loci harboured genes with drugs known as hydroxylase inhibitors, were said, “By establishing a robust model for early said,differences “By establishing a robust model for early acid and deletions with disease progression. recognised functions (IL28RA, able to almost completely reverse the and late stageimmune diabetic retinopathy, weC.would Ravindra Pushker, Jean-Marc Jacquē, Denis Shields. and late stage diabetic retinopathy, we would REL, IFIH1, TRAF3IP2, NFKBIA of symptoms ofERAP1, the disease.

Journal ofbetter Virology, Apr 2010 p3644-3653 hope to understand the progression hopeTYK2). to better understand theimplicate progression of and These findings the disease and pave the way for identifying EUROCarbDB, a research infrastructure design “When we applied these drugs to our IBD the disease and integrate pave thenew way for identifying pathways that epidermal new drug targets fortricked its 6th successful treatment”. study funded bywas the EU Framework model, the gut into thinking new drug targets for its successful treatment”. barrier dysfunction with innate and that it Programme.

Prospective users canScience access was being deprived ofdysregulation oxygen.

This activated The research was funded through adaptive immune in thethe GlycoExtractor tool funded onwhichthrough The research was Science protective pathways, incondition. turn Research prevented pathogenesis of this skin Foundation Ireland and the Health http://glycobase.nibrt.ie:8080/DemoGlycoExtra the death of the cellsand thatthe lineHealth the Research Foundation Ireland Board. ctor/mainPage. gastrointestinal tract,” explained Professor Board.

Reference Taylor. pre-clinical trial can now Reference Common“Our variants at TRAF3IP2 aredata associated with web-based interface for high product GlycoExtractor: susceptibility toApsoriatic andPharma psoriasis. inform the next phasearthritis Sigmoid Reference: processing of HPLC-Glycan data throughput Hüffmeier et al.

Nat Genet. 2010 Nov;42(11):996-9.

Reference:U cone development pipeline”.

Predominant photoreceptor dysfunction in a

Bioinformatic analysis of HIV progression studies

Success in EU FP7 call

Conway collaborator scoopsand Irishpsoriatic Times Innovation New genetic insights to psoriasis arthritis Award

Zebrafish Zebrafish model model gives gives insights insights into into diabetic diabetic blindness blindness GlycoExtractor advances glycan data manipulation

V. Artemenko, Matthew P. Campbell, and Pauline Natalia PMID: 20953186 hyperglycaemic model of non-proliferative diabetic Predominant cone photoreceptor dysfunction in a

M. addition Rudd Journal of Proteome Research, 2010, 9 (4),inpp In to the product that is currently retinopathy.

Yolanda Alvarez, Jenneth Chen, Alison hyperglycaemic model of non-proliferative diabetic 2037–2041 phase II clinical studies, Sigmoid Pharma Aretinopathy. genome-wide association study identifies new is Reynolds, Nore Waghorne, John J. O’Connor, Breandan Yolanda Alvarez, Jenneth Chen, Alison psoriasis susceptibility loci and an interaction between developing a LEDDS™-enabled formulation of Kennedy.

Disease Models & Mechanisms (2010) Reynolds, Nore Waghorne, John J. O’Connor, Breandan HLA-C andDisease ERAP1. Models Strange et al Nat Genet.

2010 Oct the hydroxylase inhibitor Kennedy. &AMechanisms (2010) 17. PMID: 20953190 dimethyloxaloylglycine (DMOG) to bring about of HIV nef areand critical in determining effective, safe targeted delivery ofthe thisrate of disease progression.

Professor Denis potential therapeutic agent.

Bioinformatic analysis of HIV progression studies