Conway Focus Issue 18 Winter 2012

Irish biopharmaceutical development New research in Nature Immunology company, Sigmoidprotein Pharma acts recently shows Pellino3 likescooped a the overall Innovation of the Year award at braking system to prevent overthe inaugural Irish Times All-Island production of interferon in response Innovation Awards.

The life-science SME, to viral by insult. highlights both a Dr founded UCD This pharmacology graduate, As a Coulter, European Centre of07/05/2010 Excellence, the Ivan actively collaborated with new physiological role for Pellino3 May 2010.qxd:Layout 1has copy 13:12 Conway Fellow, Professor Cormac and a new autoregulatory network Department of Rheumatology in StTaylor Vincent’s since being granted a Science Foundation for controlling type interferon University Hospital was1 chosen to host an Ireland industry research partnership award expression. international two-day workshop on March in 2004.

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

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

Centre of Excellence hosts international workshop

26thIrish & 27th 2010.

Sponsored by the Roche The Times award recognises stellar

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

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

Coulter said, “The collaboration with the Taylor

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

This collaboration, initiated through patients. In addition to lectures from Conway aFellows, SFI research supplement, highlights and the Professors Oliver FitzGerald

The study,

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

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

varying rates of health decline on ageing.

“When weJoint applied new drugs ourthat IBD Bone & Unitthese expressed their to hope It alsothe highlights the potential role of model, gut was tricked into thinking that it the experience of the multidisciplinary team metabolomics in of identifying biomarkers was being deprived oxygen. This activated from St Vincent’s would provide a template of healthpathways, and healthy aging”, Dr for protective which in turnsaid prevented delegates reproduce Brennan. the death ofto the cells thatsimilar line thecare and facilities for thetract,” management RA patients in gastrointestinal explainedofProfessor References Taylor.

“Our pre-clinical trial data can now their respective countries.

Claesson MJnext et al. Gut microbiota composition inform the phase Sigmoid Pharmacorrelates product with diet and health in the elderly. Nature 2012 development pipeline”. doi:10.1038/nature11319 In addition to the product that is currently in phase II clinical Sigmoid Pharma is and Siednienko J et al. studies, Pellino3 targets the IRF7 pathway developing a LEDDS™-enabled facilitates autoregulation of TLR3- andformulation viral-inducedof the hydroxylase expression of type Iinhibitor interferons. Nature Immunology 2012 dimethyloxaloylglycine (DMOG) to bring about 13 (11); doi:10.1038/ni.2429 effective, safe and targeted delivery of this potential therapeutic agent.

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

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

Conference Success

Irish biopharmaceutical developmentHewage, Conway Fellows, Dr Chandralal to the workSigmoid a the UCD Conway research team company, Pharma recently scooped Commenting award, Taylor Dr Lorraineofon Brennan andProfessor Professor wasoverall selected as the front cover image forat the said, “We are delighted forpart Dr Year Coulter and his the Innovation of the award Paul Malthouse were of the local April 2010indeed edition of the scientific journal, team and it reflects well on our the inaugural Irish Times All-Island organising the EUROMAR partnership.

Acommittee key driver offor successful BiochimicaAwards. et Biophysica Acta (BBA);SME, Innovation The life-science 2012 conference held from 27 June – 5 scientific research in 2010 is meaningful Proteinsby & Proteomics. founded UCD pharmacology graduate, Dr July in UCD. interaction of academia with industry that Ivan Coulter, has actively collaborated with

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

May

have anti-bacterial and anti-fungal properties EUROMAR is an international scientific since being granted a Science Foundation as well as the ability to advancing lysepartnership or rupture society dedicated to magnetic Ireland industry research award mammalian cells.

This850 innate immunityfrom13:12 resonance delegates in 2004. research.

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

MRI’.

More than 15,000 people in Ireland and millions of people worldwide are living with the symptoms IBD today. Current therapeutic options this chronic debilitating disease are varietyinfor ofboth solutions in order to understand the results academic outputs and the only Systems Biology Ireland (SBI) led the by very limited with surgery often being structural basis for the difference in biological application of research toward clinical product Professor Walter Kolch organised SysMed viable option.

The Sigmoid product, currently activity. development with indigenous companies.” in a phase II clinical study,conference uniquely enables 2012; an international on oral delivery of a powerful drug place without systems medicine that took in Commenting on the Taylor collaboration, Dr the This particular XT-7 peptide, isolated from causing systemic side-effects.

Carton House from 10- 13 September Coulter “The collaboration with the Taylor skin of said, Silurana tropicalis, shows potential for Under normal conditions, the gastrointestinal 2012.

Systems medicine has emerged laboratory clearly demonstrates the potential drug development as it has impressive activity thata can realised through focused as newbe approach personalised against the growth oftobacteria and Candida application ofthat basicuses research.

The development health care biological/medical albicans.

However, this potential aslike-minded an antiof a smart economy willmathematical depend on data integrated with infective agent is restricted by itsopportunities haemolytic collaborative partners identifying and computational modelling to Page 3 activity. and realising basic and applied research understand the underlying mechanisms synergies. This collaboration, initiated through of disease develop new strategies for change toand the amino acid structure of the aASFI research supplement, highlights the individualised diagnosis, and XT-7 peptide can createindigenous antreatment analogue that potential that innovative companies studies in humans have shown that non prevention. retains anti-infective but without the working with academiaproperties can realise.”

tract is lined with cells that block the contents of the gut from leaking into the intestine. In an IBD patient, this barrier is broken and the contents of the gut leak out into surrounding areas. The research team in UCD Conway used a model of IBD and, by applying a new class of drugs known as hydroxylase inhibitors, were able to almost completely reverse the symptoms of the disease.

SFI Director, Prof Mark Ferguson (left) with Dr

“When we applied these new drugs to our IBD

Chandralal Hewage at EUROMAR 2012.

Bioinformatic analysis of HIV progression studies model, the gut was tricked into thinking that it

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

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

Taylor’s collaboration with Sigmoidworkshop Pharma has Additionally, a pre-conference amino acid substitution (glycine replaced by certainly successful by these metrics However,been much of the Health research in the area with to showcased the FP-7 funded lysine) improves the therapeutic potential of of date has been based on observational or two case three co-authored publications to date in ASSET project that uses systems biology thishighest naturally occurring peptide. studies rather than scientific rigorous, systematic the ranking journals in the approaches to improve therapies forof the scientific evaluation.

This by doctoral field, Gastroenterology andwork Proceeding childhood cancers. candidate Ravindra setasout to as the National Academy ofPushker Sciences, well determine in a substantially larger sample set

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

was being deprived of oxygen. This activated protective pathways, which in turn prevented the death thecritical cells that line the of HIV nefofare in determining the rate gastrointestinal tract,” explained Professor of disease progression.

Professor Denis Taylor. pre-clinical trial dataforcan now of Shields“Our believes that searches modifiers inform the next phase Sigmoid Pharma progression rates should now focus onproduct other host and viralpipeline”. factors. “Systematic evaluation development of quantities April 2010 edition of Biochimica et Biophysica ofCover large of data by bioinformatics Acta (BBA); Proteins & Proteomics.

Incan addition product that is currently in be justto asthe important in refuting

phase II clinical studies, Sigmoid hypotheses are current in thePharma literature, (L-R) Prof Boristhat Kholodenko, SBI Deputy Director;is as developing a LEDDS™-enabled formulation of it is in discovering unknown patterns”, heProf said.

Christina Kyriakopoulou, EC Health Directorate; the hydroxylase inhibitorat SysMed 2012 Walter Kolch, SBI Director This research was funded through Science dimethyloxaloylglycine (DMOG) to bring about Foundation Ireland and University College effective, Dublin. safe and targeted delivery of this potential therapeutic agent.

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

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

A new fortnightly forum for Conway graduate

Two UCD Conway Institute teams in Irish biopharmaceutical development develop AIDS. This may reflect differences andhost, postdoctoral researchers will in bethe launched company, Sigmoid Pharma recently scooped competed very successfully Commenting on the award, Professor Taylor the viral genetics or environmental the overall Innovation of Year award at in May 2010.

Thispotentially initiative will give earlysaid, “We are delighted forthe Dr Coulter and for his factors that could be exploited inaugural Grant Thornton Corporate the inaugural Irish Times All-Island stage researchers the opportunity to talk about the treatment of the disease. team and indeed it reflects well on our 5k Team Challenge around Dublin Innovation Awards. The life-science SME, science and Aissues that concern them in an partnership. key driver of successful Docklands on Thursday, September Studies organisms have shown that foundedinbymodel UCD pharmacology graduate, Dr informal environment with refreshments scientific research in 2010 is meaningful infection with nef-deficient virus shows an 6th 2012.

The joint venture between Ivan Coulter, has actively collaborated with interaction of academia with industry that provided!

Content for the forum will be attenuated course ofand infection andThornton some Conway Fellow, Professor Cormac Taylor Athletics Ireland Grant since being granted a Science Foundation is designed to encourage social Ireland industry research partnership award running among employees from in 2004.

Dublin business communities

The Irish Times award recognises the stellar innovative performance of Sigmoid Pharma in Nearly 450 teams, comprising 1700 their application of research and development.

The companycompeted has developed twoevent new drug individuals in the that technologies, LEDDS™ and SmPill™, which not only enhance the solubility and permeability of Meta-analysis by UCD researchers led by the drug but can deliver it to targeted locations Conway Fellow, Professor Denis Shields has in the gastrointestinal tract, including the determined that there is no clear evidence colon.

differences or deletions within the nef gene.

millions peoplebasis, worldwide are living with the On a perofpatient there was no excess of symptoms IBD with today.

Current therapeutic LTNP patients one or more defective nef sequences whenchronic compared to progressors. options for this debilitating disease are decided theacademic members but it isand envisaged saw the ‘Conway Tigers’ home results in by both the in While the high frequency ofcoming amino very limited with surgery outputs often beingacid the only that it will include a mix of technology application of research toward clinical product 5th place inatThe the mixed residues category and two replacement particular indicative viable option.

Sigmoid product,iscurrently development with indigenous companies.” overviews, informal and formal in research evolvement, permutation testing of Conway finishing 7th place in arapid phase II runners clinical study, uniquely enables seminars, PhD rehearsals and careerDr showed that residues with drug more replacements in the men’s and women’s races.

Commenting on the Taylor collaboration, oral delivery of aviva powerful without than expected were not statistically development talks from within and beyond Coulter said, “The collaboration withsignificant. the Taylor causing systemic side-effects. laboratory clearly demonstrates the potential academia.

Forum committee members, PhD The researchers conclude that current data Event ambassador; Olympian and former Under normal conditions, gastrointestinal that can be through focused student Mr Thomas Schwarzl provides norealised evidence thatthe individual residues

London Marathon winner Catherina

application of basic research. The development McKiernan said “The ofon thelike-minded event of a smart economy willspirit depend was fantastic.

It wasidentifying a welcoming sight collaborative partners opportunities and realising basicrunners and applied research to see so many complete the synergies.

This also collaboration, initiated through course, while managing to enjoy a SFI research supplement, highlights the themselves at the same time”. potential that innovative indigenous companies working with academia can realise.”

(thomas.scharzl@ucd.ie and postdoctoral tract is lined with cells that) block the contents Reference: Meta-analysis to Dr test the association HIV-1 nef amino researchers, David Gomez of the gut from leaking into theofintestine.

In an acid patient, differences andbarrier deletions with disease progression.

IBD this isand broken and the (david.gomez@ucd.ie) Dr Craig Slattery Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields. contents of the gut leak out intosuggestions surroundingfor (craig.slattery@ucd.ie invite Journal of Virology, Apr 2010) p3644-3653 areas. The research team in UCD Conway used the forum schedule. a model of IBD and, by applying a new class of drugs known as hydroxylase inhibitors, were able to almost completely reverse the symptoms of the disease.

“When we applied these new drugs to our IBD (L-R) Representing UCD Conway Institute: Claire model, the gut was tricked into thinking that it Robinson, Aidan Boland, Maike Jurgens, Dan Dowling, was being deprived of oxygen. This activated Roisin Neary, Dara Lundon, Paddy O’Leary, Leona protective pathways, which in turn prevented Connolly the death of the cells that line the gastrointestinal tract,” explained Professor Taylor. “Our pre-clinical trial data can now inform phase Sigmoid Pharma of HIVthe nefnext are critical in determining theproduct rate development pipeline”. Professor Denis of disease progression.

Bioinformatic analysis of HIV progression studies

that particular defective viral sequences in

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

maintain stable CD4 lymphocyte counts and

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

Taylor’s collaboration with Sigmoid Pharma has studies inbeen humans have shown thatmetrics non with certainly successful by these progression was associated with three co-authored publications to gross date in two of believes searches modifiers deletions the nef scientific gene.

InShields addition to the that product that isfor currently in of the highestinranking journals in the progression rates shouldSigmoid now focus on other phase II clinical studies, Pharma is field, Gastroenterology and Proceeding of the However, much of the research in the area to Elaine Quinn host and viral factors. “Systematic evaluation developing a LEDDS™-enabled formulation of National Academy of Sciences, as well as the date has been based on observational or case Communications Education Officer the hydroxylase inhibitor generation of proprietary innovative products of large quantities of data by&bioinformatics studies rather than rigorous, systematic Biomolecular &inBiomedical Research dimethyloxaloylglycine (DMOG) to bring about and the creation of high-skilled jobs.UCD Conway Institute can beofjust as important refuting scientific evaluation. This work by doctoral effective, safethat andare targeted delivery of thisDublin University College hypotheses current in the literature, as More than 15,000 people in Ireland and candidate Ravindra Pushker set out to potential therapeuticunknown agent. patterns”, Belfield, Dublin it is in discovering he said.4 millions of people worldwide are living with the determine in a substantially larger sample set Ireland symptoms IBD today. Current therapeutic if any association exists between disease This research was funded through Science options for this chronic debilitating disease are progression and particular amino acid Foundation Ireland and University College E: elaine.quinn@ucd.ie very limited with surgery often being the only differences orThe deletions within the nef gene.

Dublin.

T: (+353-1) 716 6706 viable option.

Sigmoid product, currently F: (+353-1) 716 6701 in a phase II clinical study, uniquely enables On a per patient basis, there was no excess of oral delivery of a powerful drug without W: www.ucd.ie/conway LTNP patients with one or more defective nef causing systemic side-effects.

sequences when compared to progressors.

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

Reference:

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

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

disease (CKD) and improve patient treatment, Conway researchers led by Dr. Tara McMorrow and Professor Michael Ryan have with particular focus on CKD arising from diabetes and hypertension. The multisuccessfully secured €485,500 in funding as disciplinary research consortium has 25 part of an overall award to the Systems partners (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney May 2010.qxd:Layout 1 copy(SysKid) 07/05/2010from 13:12 Pageand 3 the project is due to run 15 countries Disease Diagnosis and Treatment for five years. consortium under the European Union FP7 programme.

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

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

GlycoExtractor advances glycan data manipulation cells, tissues and fluids.

EUROCarbDB, a research infrastructure design Glycomics needs the supporting framework of extensive, well-curated databases and study funded by the EU 6th Framework Commercial packages that support HPLC Programme. Prospective users can access the flexible analytical tools. Currently, this field instruments cannot facilitate the extraction of GlycoExtractor tool on of study lacks the established, large quantities of data. In an effort to alleviate comprehensive and centralised data http://glycobase.nibrt.ie:8080/DemoGlycoExtra this bottleneck within high-throughput collections, standards and information ctor/mainPage. glycomic projects, the NIBRT team have reporting protocols that exist within Reference developed a web-based tool that interfaces GlycoExtractor: A web-based interface for high genomics and proteomics. with the Waters chromatography software tract is lined cells that block ‘Early thediabetes, contents results in both academic outputs and the Irish biopharmaceutical development throughput processing ofwith HPLC-Glycan data Research by Conway Fellow, Dr Oliver the function of worm Arl13b causes the complex traits including obesity, collaborative project entitled weight gain of 12.2kg among women who Women who choose a low glycaemic package to application improve and automate the and export Researchers, Dr Natalia has Artemenko and Drrecently Natalia V. of Artemenko, Matthew P. and Campbell, Pauline In an the gut from leaking into theand intestine. ofaresearch toward clinical product company, Sigmoid Pharma scooped Blacque revealed new information ciliary membrane to bulge become mental retardation even cancer.

Nutrition’ that aims to provide changed to low GI diet. index (GI) diet from early pregnancy will of Proteome Research, 2010, 9 and (4), pp Matthew Campbell from the Nationalof Institute file formats for subsequent IBD patient, this barrier is broken the development with indigenous companies.” M. Rudd Journal the overall Innovation the Year awardofatdata to various about a the gene implicatedof inexcessive Joubert gestamisshapen as well as affecting the ability 2037–2041 of evidence-based for reduce likelihood analysis. The modular architecture of the tool of Bioprocessing &Irish Training contents ofBlacque the gutrecommendations leak outthat intothese surrounding theResearch inaugural Times(NIBRT) All-Island Dr Oliver hopes findings models to identify processes involved in early disease (CKD) and improve patient treatment, Conway researchers led by Dr. Tara Commenting onon Taylor collaboration, Dr syndrome and related cerebellar other totheproperly distribute within optimal nutrition that incorporates Commenting the findings, Professor gain and maternal glucose led by Conwaytional Fellow,weight Professor Pauline Rudd disorders also facilitates theproteins manipulation of data from areas.

Theearly research team in UCD Conway used Innovation Awards.

The life-science SME, will ultimately lead to a greater CKD progression and investigate novel McMorrow and(JSRDs), Professor Michael Ryan with particular focus on CKD arising from Coulter said, “The collaboration with the Taylor by have bone the ciliary membrane. other systems. have developed an openbycharacterised access, web-based health Health McAuliffe said, “Excessive weight gain along-term model of IBD and,outcomes. by applyingWorld a new class founded UCD pharmacology graduate, Dr data management intolerance according to ablindness, research study understanding not of JSRDs, alsoof laboratory clearlyThe demonstrates the potentialstrategies for preventing andonly slowing the butwere diabetes and hypertension. multisuccessfully €485,500 inquerying funding as abnormalities, cystic kidneys, interface that secured facilitates extraction, drugs known asstatistics hydroxylase inhibitors, Ivan Coulter, haswomen actively collaborated with Organisation instudies 2010 highlighted during pregnancy is associated with an involving 800 attending the The NIBRT team are now working to integrate They also found that a fully functional of closely related ciliopathies such as that can be realised through focused progression of the disease.

These will disciplinary research consortium has 25 partsharing of an overall award to the Systems and of developmental HPLC-glycan data generated in of Taylor able to almost completely reverse the were Conway Fellow, Professor delay andCormac loss muscle 43 million children under five years increased need for delivery by National Maternity Hospital, Dublin.

GlycoExtractor withprotein the of EUROCarbDB basic research.

Arl13b needed forThe thedevelopment normal be integrated Meckel Gruber Bardet-Biedl syndrome, with clinical and epidemiological high throughput processes. symptoms of theand disease. since being granted a Science (16application universities, 9isindustry partners) Biology towards Novel Chronic Kidney tone and control.

The findingsFoundation of thispartners framework of to provide a comprehensive highoverweight.

Childhood obesity predisposes Caesarean section, a higher likelihood of a smart economy will depend on like-minded functioning of a protein transport system in as well as perhaps more common studies across the consortium using systems Ireland industry research partnership award from 15 countries and the project is due to run Disease Diagnosis and Treatment (SysKid) research, funded through Science throughput collaborative HPLCpregnancy data analysis platform foropportunities Glycosylation is the most common and aFionnuala “When we applied new drugsdiseases our IBD partners identifying individuals to other childhood post weight retention, and abiology methodologies Conway Fellow, Professor in 2004. in these order to develop cilia.

This intraflagellar transport system phenotypes associated with ciliumtonew for years. consortiumdiverse under the European FP7 of Ireland Foundation IrelandUnion President structurally post-translational the five storage andrealising annotation ofand experimental model, the gut was tricked into thinking that it and basic applied research and premature death.

Being overweight higher predisposition to obesity in later life.

McAuliffe led the randomised control trial diagnostic strategies and treatment options to (IFT) makes contact with theinitiated ciliary through dysfunction such as and The Irish Times recognises stellar programme.ofYoung data.

The integration of next generation modification proteins.

Moreaward than half of(PIYRA) all the to was being deprived of mental oxygen. retardation This activated synergies.

This collaboration, Researcher Award Oliver The UCD Conway team, including postdoctoral and obese is the 5thwhich leading risk for deaths development. of 800 women without diabetes on their innovative performance Sigmoid Pharma in on results, the they prevent CKD obesity. gene products Blacque, have been shown to beofpublished bioinformatic tools will Based further thethese protective pathways,Email in turn prevented amembrane.

SFI research supplement, highlights were recently in the researchers Dr. and indigenous Dr. Natalia Syskid (www.SysKid.eu) was established to development. their many application of research and tara.mcmorrow@ucd.ie for details ofthe a PhD globally.

This research hasworking shown that switching to second pregnancy who previously delivered proposed aSlattery new model for Arl13b, glycosylated.

With glycans or development of Craig unified approaches for the death of the cells that line potential that innovative companies Journal of specific Cell Biology.

He notes “That Arl13b associates with ciliary Theinfant company two 4kg. new drug Martin, culture and animal position gastrointestinal currently available. further our understanding ofhas chronic kidney glycoforms showing potential asdeveloped cancer handlingwill large scale glycomics initiatives autilise low GI diet in pregnancy is a membrane simple, safe tract,” explained Professor working with academia can realise.” where itcell functions atdata the ciliary an weighing more than technologies, LEDDS™ andto SmPill™, which membranes and is required for cilium withnot applications in biomarker discovery biomarkers, there increasing Taylor.

“OurNutrition’ pre-clinical trial data can now The ‘Early project teams, including & effective measure to improve maternal Oneisofanseven genes need associated with JSRDs, to regulate important ciliary membrane Taylor’s collaboration with Sigmoid Pharma has researchers only enhance the solubility and permeability of NIBRT Dr Matthew Campbell and Dr Natalia structure/function in both worms develop high throughput, highly sensitive and inform the next phase Sigmoid Pharma product Arl13b codes fordeliver a protein already known toresearch properties such as shape, transmembrane 30 academic partners, 3 industryand partners glucose homeostasis and reduce 400 women continued to follow their This was partially supported by certainly been successful by these metrics with Artemenko who developed GlycoExtractor the drug but can it to targeted locations robust strategies that detail the glycome of development pipeline”. mammals demonstrates the remarkable play in thepattern formation and/or function protein distributions and IFT. to date in two of and 4 small-medium enterprises, are gestational weight gain.” three co-authored publications normal dietary throughout the in theroles gastrointestinal tract, including the evolutionary conservation ofishow this small In addition to the product that currently in the highest ranking scientific journals in the of cilia, which are hair-like projections colon. exploring current key hypotheses on the pregnancy without being given any specific Up to only 20 years ago, many believed G-protein functions.” phase II clinical studies, Sigmoid Pharma is field, Gastroenterology and Proceeding of the extending from the surface of the cell. likely cases and pathways of early programGestational weight gain is one of several advice on gestational weight gain.

The Sigmoid Pharma-Taylor collaboration is most cilia to be redundant cellular developing a LEDDS™-enabled formulation of National Academy of Sciences, as well as the However, molecular details of Reference ming of obesityinhibitor risk. factors influencing infant birth weight. facilitating the the precise development of a new the hydroxylase generation of proprietary innovative productsEUROCarbDB, organelles that have fallen victim to cells, tissues and fluids. asyndrome research infrastructure design Glycomics needs the supporting framework Joubert Arl13b functions at ciliary what exactlyapproach Arl13b is in cilia have therapeutic fordoing the treatment of Macrosomic or ‘large for gestational age’ 400 women attended a dietary education dimethyloxaloylglycine (DMOG) to bring and the creation of high-skilled jobs. mammalian evolution a type of cellular membranes and stabilizes protein transport in about of extensive, well-curated databases and study funded by the EU 6th Framework remained unclear. inflammatory bowel disease (IBD) by bringing packages that support infants areWe predisposed to a variety of Programme. effective, safe elegans. and targeted delivery ofthe thisOI, session with the research dietician atCommercial 16 Caenorhabditis Cevikcan S, Hori Y, Kaplan appendix. now knowHPLC these cellular flexible analytical tools.

Currently, this field Prospective users access Reference: More than 15,000 people inthat Ireland and together the research methodology of the potential therapeutic agent. instruments facilitate the extraction ofoutcomes, the research, Dr Kennedy tocannot die asobstetric a result of the raised New research Blacque’s led by to Conway Fellow Dr Kida K,on Toivenon C, Cottell D, Katada T, adverse and neonatal inform them of healthy eating team studied thethe gene in themost cilia likely millions antennae on nearly all of ourwith cellsCommenting of study lacks weeks the established, GlycoExtractor tool on T, Foley-Fisher ofpresent people worldwide are living the Taylor group withthat the treatment proprietary Walsh, McGowan, Mahony, ME glucose levels inlikely diabetes.

Breandán Kennedy indicates Kontani K, CBlacque OE. JRCell Biol. 2010 Mar 22; said, “ByJM establishing a robust model forFoley, early large quantities of data.

Intoday. an to alleviate areseen more to effort beCurrent obese in childhood, guidelines in pregnancy andsystem, encourage symptoms IBD therapeutic http://glycobase.nibrt.ie:8080/DemoGlycoExtra comprehensiveof and centralised data tiny worms (Caenorhabditis elegans) and serve fundamental roles in many liquid/emulsion drug delivery Low glycaemic indexwe dietwould in pregnancy of diabetic blindness should look at 188(6):953-69 and lateFMcAuliffe. stage diabetic retinopathy, this bottleneck within high-throughput adolescence and early adulthood and are at options for this chronic debilitating disease are them to choose low glycaemic index foods Dr Kennedy and his team found that new blood collections, standards and information ctor/mainPage.

LEDDS®, developed by Sigmoid Pharma. collaborators in for the colour University of motility and sensory functions, including hope to to prevent macrosomia (ROLO study): randomised protecting the while neurons responsible better understand the progression of glycomicand projects, therisk NIBRT team often have very limited with surgery the only vessels neuronal cell death in diabetic control trial. BMJ 2012;345:e5605 doi:10.1136/bmj. athe greater of cardiovascular & metabolic reporting protocols that exist within such as high fibre cereal and brown rice Tokyo conducted parallel in signalling pathways critical tobeing development.

Reference vision in the eye and not just targeting the the disease and pave the way for identifying Commenting on the award,experiments Professor Taylor developed a web-based tool that interfaces viable option.

The Sigmoid product, currently retinopathy can arise independently of each e5605A(30 August 2012) GlycoExtractor: web-based interface for high genomics and cultured proteomics. complications later in life. without reducing their calorie intake.

This human cells.

Together, theyand blood vessels as is“We currently the practice. said, are1delighted Dr Coulter his drug targets for its successful treatment”. with the chromatography software May 2010.qxd:Layout copy for07/05/2010 13:12 3not in a phase II identified clinical study, uniquely enables other.

In Waters addition, they that cone It Page is now surprising that defects in new throughput processing of HPLC-Glycan data confirmed that Arl13b proteins uses lipid group had two follow up sessions at 28 and team and indeed it reflects well on our oral delivery of a powerful drug without Researchers, Dr Natalia package to cilium improve and those automate the export Natalia V. Artemenko, Campbell, and Pauline photoreceptor neurons, inare associated Nearly 2.5 million peopleArtemenko worldwideand are Dr blind structure andinvolved function research was Matthew funded P.through Science partnership.

AThis key driver of the successful However, this study that a low The anchors associate with ciliary 34 weeks gestation to reinforce this colour lowdata GI vision M. Rudd Journal of Proteome Research, 2010, 9 (4), pp causing systemic side-effects. andanused inexpanding daylight, are most due to diabetic retinopathy. secondary Matthew Campbell fromtothe National Institute of to various file formats forshowed subsequent Foundation Ireland and the Health Research with ever range of human scientific research in 2010 is meaningful 2037–2041 glycaemic index diet inofpregnancy not diet regimen. affected themodular high glucose levels. complication ofmembrane. diabetes activates the growth of Bioprocessing Research & Training (NIBRT) analysis.by The architecture the tool did Board. to identify processes involved in early Under conditions, the gastrointestinal diseases and syndromes, collectively called interaction academia industry that disease (CKD) andnormal improve patientoftreatment, models Conwayleaky researchers ledof byin Dr. of blood vessels theTara eye with andRudd is reduce the incidence ‘large for lednew

by Conway Fellow, Professor Pauline also research facilitates the manipulation of data from The team made their observations Much of the work on the project was carried ciliopathies, which have overlapping clinical CKD progression and investigate novel McMorrow and Professor Michael Ryan have with particular focus on CKD arising from responsible for the death of photoreceptors, gestational age’ infants in a group of strategies for preventing and slowing the of theweb-based research, published in data have developedThe an findings open access, other management systems. using a novel zebrafish ofmultidiabetes, and hypertension. outsend

by UCD doctoral features suchmodel asThe polycystic kidneys and Reference: successfully secured €485,500 in candidate, funding the neurons that visual messages to ourasSebihadiabetes interface that facilitates extraction, querying women atconsortium riskdegeneration, of foetal the British Journal, showed an which resembles the early stages of macrosomia. diabetic progression of the disease. These studies will disciplinary research has 25bone part of an overall award to the Cevik.

She Medical and herSystems colleagues went on to NIBRT livers, retinal brain.

The team are now working to integrate Predominant cone photoreceptor dysfunction in a and sharing of HPLC-glycan data generated in retinopathy in humans.

It is an exciting be integrated model with clinical and epidemiological average gain of 13.7kg among partners (16abnormalities, universities, 9hydrocephalus, industry partners) Biology towards Novelweight Chronic Kidney hyperglycaemic of non-proliferative diabetic demonstrate in C. elegans how disrupting as well as Arl13b at ciliary membrane GlycoExtractor with the EUROCarbDB development forresearch the group who now hope torun and Until now,Diagnosis it was unclear if the changes high throughput processes. studies across theAlvarez, consortium systems This by Professor McAuliffe retinopathy.

Yolanda Jenneth using Chen, Alison 15 countries and the project is due to women remained ontotheir usualfrom diet Disease andwho Treatment (SysKid) framework to provide a comprehensive highfurther their research and establish a vessels and neurons occurred independently biology in order to develop new Reynolds,methodologies Nore Waghorne, John J. O’Connor, Breandan for five extend years. consortium under the European Union FP7 of an average her team is part of a wider EU FP7 funded during their pregnancy, against throughput HPLC data analysis platform for Glycosylation is the most common and model of late stage diabetic disease. one other and which type of retinal neuron is Kennedy. Disease Models and & Mechanisms diagnostic strategies treatment(2010) options to programme. structurally diverse post-translational the storage and annotation of experimental The UCD Conway team, including postdoctoral prevent CKD development. Email modification ofMeta-analysis proteins. More than oftoall led researchers data. The integration next generation Dr. Craig Slattery and Dr. Natalia Syskid (www.SysKid.eu) wasby established for details of a PhD the rate UCDhalf researchers by of HIV nef are critical in determining studies in of humans have shown that non tara.mcmorrow@ucd.ie gene products have been shown to bekidney bioinformatic toolscell willculture further the animal Martin, utilise and position currently further our understanding of chronic Conway Fellow, Professor Denis Shields has will progression of diseaseavailable. progression. Professor Denis was associated with gross glycosylated. With many specific glycans developmentdeletions of unified approaches determined that there is no or clear evidence Shields believes that searches for modifiers of in the nef gene. for viral you sequences in progression rates should focus onMSc otherin larger programmes suchnow as the new We scale introduced 4 new advanced core Ithat amparticular delighted to welcome to thehandling large glycomics data initiatives glycoforms showing potentialdefective as cancer However, much of the research in the area to the is HIV-1 nef gene certain ofwith the applications host and commencing viral factors. “Systematic evaluation in biomarker discovery biomarkers, there an Focus increasing need to regions technology modules onobservational a pilot basis or this Conway andorlook forward to working Imaging in September 2010. date has been based on case protein playhighly a significant role in disease of largeDrquantities of data by Matthew Campbell andbioinformatics Dr Natalia develop high throughput, sensitive and academic year;than those covering principlesNIBRT researchers studies rather rigorous, systematic with you in the coming months!

This research was partially supported by progression. just asGlycoExtractor important in refuting Artemenko can who be developed robust strategies that detail the glycome of scientific evaluation.

This work by doctoral and practical aspects of imaging and applied Ihypotheses hope that athat number of new initiatives, current inInstitute thethe literature, tract isaligned lined with cells that block contents results in bothsessions academicfocused outputs on andindustry the Irish biopharmaceutical development Welcome! open forum areas toare that of the will as HIV-infected patients can be categorised on candidate Ravindra Pushker set out to will run proteomics in late March and it the is ingut unknown patterns”, heInsaid. of from leaking into the intestine. an application ofbegan research toward clinical product company, Sigmoid recently scooped tissues As an institute withPharma an increasingly including the early-stage researcher forum and fluids.

EUROCarbDB, adiscovering research infrastructure design Glycomics needs framework engagement gender issues impacting undoubtedly provide valuable critique the the basissupporting of the number of years it takescells, for determine in aand substantially larger sample set until mid-June with a furthercompanies.” two modulesstudy in funded IBD patient, this barrier is will broken and the development with indigenous the overall Innovation of and the Yearand award at by the EU 6th Framework of extensive, well-curated databases interdisciplinary research focus described in this issue, not only The quarter has been a busy time for early career researchers.

More detail on the of our research and innovation strategy themlast to progress to AIDS. Some patients if any association exists between disease This research was funded through Science packages that support HPLC contents of the gutusers leak out surrounding the inaugural Irish Times Programme.

Prospective caninto access the flexible analytical tools.

Currently, thisAll-Island field counts Commercial genomics and flow taking maintain stable lymphocyte and progression particular amino acid place Foundation Ireland and University College Commenting onread the Taylor Dr expertise inAwards. specialist platforms, event can beand incytometry thiscollaboration, issue.

Institute.

I CD4 congratulate all those who as wellThe as research recommendations on futureused instruments cannot facilitate the extraction of strengthen the of Conway areas. team in UCD Conway Innovation Thetechnology life-science SME, of study lacks the thenot established, GlycoExtractor tool on community over week-long periods during the summer do go on to develop AIDS even after more differences or deletions within the nef gene.

Dublin.

Coulter said, “The collaboration with the Taylor large quantities of data.

In an effort to alleviate participated in the annual UCD Conway direction. we are uniquely placed to participate in the a model of IBD and, by applying a new class of founded by UCD pharmacology graduate, Dr researchers and forge new interdisciplinary comprehensivethan and10centralised data http://glycobase.nibrt.ie:8080/DemoGlycoExtra years of infection. months. laboratory clearly demonstrates the potential this high-throughput drugs known as hydroxylase inhibitors, were Ivan Coulter, has actively collaborated with bottleneck Festival of Research &ofInnovation Members of the newly constituted On awithin per patient basis, there was no excess ctor/mainPage. of collections, standards and information education and training the next onglycomic links but will celebrate and heighten that can the be realised through focused projects, NIBRT to almost completely reverse the Conway Fellow, Professor Taylor Scientists are curious to Cormac why these longLTNP patients with team one orhave more defective nef reporting protocols that exist within Referenceable September 20th andasespecially the 2012 scientific advisory board forThe the Institute Professor Walter Kolch generation of research scientists.

The newly application of basic research. development awareness of our research and innovation developed a web-based tool that interfaces Commenting on the research, Dr Kennedy most likely to die as a result of the raised New research led by Conway Fellow Dr We hope towhen determine fromtothis pilot if GlycoExtractor: symptoms of the interface disease.for high since beingprogressor granted a (LTNP) Sciencepatients Foundation term, nondo not sequences compared progressors.

A web-based genomics and UCD proteomics.

Conway Festival medal winner,award met Conway Fellows and representatives of aseen smart economy willsoftware depend on like-minded with Waters chromatography Reference: launched PhD This programme in Bioinformatics glucose diabetes.

Breandán Kennedy indicates that treatment processing of HPLC-Glycan data for early throughput said, “ByDirector establishing a robust model successes.

Ireland industry research partnership develop AIDS. may reflect differences in the levels While thein high frequency ofwithin aminoUCD acid as well demand for training from “When we applied these new drugs to nef ouramino IBD collaborative partners identifying opportunities Meta-analysis to test the association of HIV-1 Kate Byrne.

In addition to celebrating of their research teams during the course Researchers, Dr Natalia Artemenko and Dr package to improve and automate the export V. Artemenko, Matthew P. Campbell, and Pauline Natalia of diabetic blindness should look atrecently in lateJournal stage ofdiabetic retinopathy, we would the2004. host, viral Biology genetics or environmental replacement at particular residues is indicative and Systems attractedDr80Kennedyand as from external academic centres and and acid differences and deletions with disease progression.

M. Rudd Proteome Research, 2010, 9 (4), pp that it model, the gut was tricked into thinking realising basic and applied research and his team found that new blood Matthew Campbell from the National Institute of data to various file formats for subsequent the achievements of Conway researchers of the first meeting on October 8th & protecting the EU neurons responsible for colour factors that could potentially be exploited for of rapid evolvement, permutation testing hope to better understand the progression of TheResearch Irish120 Times awardapplicants recognises theup stellar Ravindra Pushker, Jean-Marc Jacquē,This Denisactivated C. Shields.

2037–2041 Professor Walter Kolch and non-EU for to 15 and industry will dictate stand-alone delivery of was being deprived of oxygen. synergies.

This collaboration, initiated through analysis.

The modular architecture of the tool of Bioprocessing & (NIBRT) vessels the neuronal cell death inmore diabetic in previous year, the programme 9th in the This group of leading thethe treatment ofTraining the disease. showed thatInstitute. residues with replacements Journal Virology, Apr 2010 p3644-3653 vision in the eye and notperformance just targeting the innovative of Sigmoid infacilitates the disease andofpave the way for identifying protective pathways, which in turn prevented athese SFIthe research supplement, highlights thewithin led by Conwaystudentships.

Fellow, Professor Pauline Rudd Pharma also manipulation ofstatistically data from significant. advanced modules or inclusion Director, UCD Conway Institute retinopathy can arise independently of each than expected were not to incorporate two dedicated international scientistsindigenous from research blooddeveloped vessels expanded asanisopen currently the practice. their application oforganisms research and new drug forthe itscells successful thetargets death of that linetreatment”. the potential thatidentified innovative Studies in model havedevelopment. shownother that data have access, web-based management systems.that other.

In addition, they cone companies The company has developed two shows new drug gastrointestinal tract,” explained Professor working with academia canthat realise.” infection with nef-deficient virus an Theneurons, researchers conclude current data interface facilitates extraction, querying photoreceptor those involved in Nearly 2.5that million people worldwide are blind Thenot NIBRT team are no now working toindividual integrate residues LEDDS™ and SmPill™, which The research through Taylor.was “Ourfunded pre-clinical trial Science data can now provides evidence that attenuated course infection and and sharing of technologies, HPLC-glycan dataofgenerated in some colour and used daylight, most Pharma Foundation due to diabeticonly retinopathy.

This secondary Taylor’s collaboration withare Sigmoid has GlycoExtractor with the in EUROCarbDB enhance the solubility and permeability of vision Ireland andphase the Health Research inform the next Sigmoid Pharma product high throughput processes. successful affected by certainly theprovide highbeen glucose levels. by these complication ofthe diabetes activates the itgrowth framework to a comprehensive high-metrics with drug but can deliver to targeted locations Board. development pipeline”. publications Glycosylation isinthe most common and HPLCco-authored data analysis platform to fordate in two of thevessels gastrointestinal tract, thethroughput three of new leaky blood in the eye andincluding is

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

Success in EU FP7 call

GlycoExtractor advances glycan data manipulation

Zebrafish model gives insights into diabetic blindness

Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Director’s Message

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

Zebrafish model gives insights into diabetic blindness

UCD CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH

Conway collaborator scoops Irish Times Innovation Award Conway collaborator Irish Times Innovation Award 2012 UCD Conway Festival scoops of Research & Innovation Irish biopharmaceutical development Doctoral candidate, Kate Byrnescooped was company, Sigmoid Pharma recently Irish biopharmaceutical development the overallSigmoid Innovation of theConway Year award at awarded the 2012 UCD company, Pharma recently scooped the inaugural Irish Times All-Island overall of&the Year awardgold at Festival ofInnovation Research Innovation the inaugural Irish Times All-Island Innovation Awards.

The SME, medal, sponsored by life-science Roche for her Innovation Awards.

Thealife-science SME,Dr founded byto UCD pharmacology graduate, research develop mathematical founded

by UCD graduate, Dr Ivan Coulter, haspharmacology actively collaborated with model describing the signalling Ivan Coulter, hasProfessor actively collaborated with Conway Fellow, Cormaccancer Taylor network activity controlling Conway Fellow, Professor Cormac Taylor since being granted a Science Foundation cell migration. since being granted a Science Foundation Ireland industry research partnership award Ireland industry research partnership award in 2004.

Kate is carrying out her studies under in 2004. the Irish supervision of Professor Boris The Times award recognises the stellar The Irish Times recognises the stellar Kholodenko inaward Systems Ireland innovative performance of Biology Sigmoid Pharma in innovative performance of Sigmoid Pharma and UCD Conway Institute. initiallyin their application of research andShe development. their application of research and development. woncompany the systems biology moderated The has developed two new drug The company has before developed two new drug poster category joining fivewhich othernot technologies, LEDDS™ and SmPill™, SmPill™, which technologies, LEDDS™ not category winners for and a Dragons’ Den only enhance the solubility and permeability of only enhance the solubility andoverview permeability style finale. Kate’s concise of of the drug but can deliver it to targeted locations the drug but can deliver it to targeted locations her project and its innovative potential in tract, including the in the the gastrointestinal gastrointestinal including most impressed thetract, judging panel.the May 2010.qxd:Layout 1 copy 07/05/2010 13:12 colon. colon.

Cell migration is vital for cancer The collaboration is is The Sigmoid Sigmoid Pharma-Taylor Pharma-Taylor collaboration cells to invade and metastasise.

The facilitating the development of a new process is controlled by the dynamic therapeutic approach for the treatment of interaction between two members of inflammatory bowel disease (IBD) by bringing the same family of signalling proteins; methodology of the together research Rac1 andtheRhoA, via an intermediary proprietary Taylor with the namedgroup PAK.Kate Byrne has developed a liquid/emulsion drug delivery system, how mathematical model that describes LEDDS®, developed by Sigmoid Pharma.

LEDDS®, developed by Sigmoid Pharma. and these two signalling proteins interact

validated this using experimental Commenting onmodel the award, Commenting on the award, Professor Professor Taylor Taylor data fromare a breast cancer cell line.and his said, “We “We delighted for said, are delighted for Dr Dr Coulter Coulter and his team and and indeed indeed it it reflects team reflects well well on on our our partnership. A A key key driver driver of partnership. of successful successful scientific research in 2010 is meaningful scientific research in 2010 is meaningful interaction of academia with industry that interaction of academia with industry that

results in both academic outputs and the “We were to arrest cellclinical migration application ofable research toward product results in both academic outputs and the completely causing PAKcompanies.” inhibition and development with indigenous application ofby research toward clinical product then maintain this using low inhibitor development with indigenous companies.”

Commenting on the Taylor of collaboration, Dr concentrations because the bistable Commenting onsignalling thecollaboration Taylornetwork”, collaboration, Dr Coulter of said, with the nature the“The sheTaylor Coulter said, “The demonstrates collaboration with the Taylor laboratory clearly the potential said. laboratory demonstrates the potential that can beclearly realised through focused that can be of realised through application basic research.

The development This research shows early focused indications application ofa basic research. development of a smart will depend on like-minded that PAK iseconomy desirable drugThe target of a smart will depend on like-minded given thateconomy cell migration is completely collaborative partners identifying opportunities collaborative partners identifying opportunities dependent PAKand activity. and realisingon basic applied research and realising basic and appliedinitiated researchthrough synergies.

This collaboration, synergies.

This collaboration, initiated New to the 2012 festivalthrough a SFI additions research supplement, highlights the a SFI researchwere supplement, highlights the programme two open forum potential that innovative indigenous companies potential that indigenous companies sessions.

Theinnovative early career researcher open working with academia can realise.” working presented with academia can realise.” with the forum, in conjunction Taylor’s collaboration with Sigmoid Pharma Pharma has UCD Research Staffwith Association, raised has Taylor’s collaboration Sigmoid many ofbeen the issues facing women certainly been successful by young these metrics metrics with certainly successful by these with in science today.publications The gender-science three co-authored publications to date date in in two two of of three co-authored to 3 ranking relationship is a particularly relevant thePage highest scientific journals journals in the the the highest ranking scientific in topic in the context of the Europeanof field, Gastroenterology Gastroenterology and Proceeding of the the field, and Proceeding Commission proposed framework National Academy Academy of Sciences, Sciences, as well wellfor as the the National of as as Horizon 2020 that will highlight generation of proprietary innovative the products innovative products need to use the potential andjobs. talent high-skilled jobs. and the creation of high-skilled

pool of women more extensively and effectively.

The session fostering More than 15,000 people inon Ireland and Ireland and industry-academia engagement was also millions of people worldwide are with the worldwide are living living with the timely given increasing emphasis symptoms IBDthe today.

Current Current therapeutic therapeutic funding agencies are placing on disease industry options this debilitating options for for this chronic chronic debilitating disease are are collaboration academic very often being very limited limited with withinsurgery surgery oftenresearch. being the the only only Dr Conor Hanly, ResMedproduct, Inc; Dr Ivan viable currently viable option. option. The The Sigmoid Sigmoid product, currently Coulter, and Drenables Elaine in a phaseSigmoid II clinicalPharma study, uniquely in a phase II clinical study, uniquely enables oral oral delivery delivery of of aa powerful powerful drug drug without without causing causing systemic systemic side-effects. side-effects.

tract is lined with cells that block the contents of theisgut from into the intestine.

In an Harris, Innovation21 hadblock valuable tract lined withleaking cells that the contents insights how scientists canand work IBD this barrier is broken theIn an of thepatient, gut into from leaking into the intestine. withpatient, industry successfully. contents of the leakisout into surrounding IBD thisgut barrier broken and the contents of research the gut leak out areas. The team in into UCDsurrounding Conway used Zenaand, Werb, University of class areas.

The team in UCD aConway usedof aProfessor model ofresearch IBD by applying new California San Francisco; Professor adrugs modelknown of IBD by applying a new class asand, hydroxylase inhibitors, wereof Finian Martin, UCD andreverse Drinhibitors, Eileen drugs ascompletely hydroxylase able toknown almost the were Furlong, European Molecular able to almost completely reverse Biology the symptoms of the disease.

Laboratory Heidelberg were the symptoms of (EMBL), the disease.

“When wepresenters applied these to our IBD keynote at new the drugs conference “When we these drugs to ourthat IBDit on September 20th innew UCD Conway model, theapplied gut was tricked into thinking model, the deprived gut was tricked into This thinking that it Institute. was being of oxygen. activated was being deprived of oxygen. This activated protective pathways, which in turn prevented protective pathways, which in turn prevented the death of the cells that line the the death of the cells that line the gastrointestinal tract,” explained Professor gastrointestinal tract,” explained Professor Taylor. “Our “Our pre-clinical pre-clinical trial trial data data can can now now Taylor. inform the the next next phase phase Sigmoid Sigmoid Pharma Pharma product product inform development pipeline”. pipeline”. development In addition addition to to the the product product that that isis currently currently in in In phase IIII clinical clinical studies, studies, Sigmoid Sigmoid Pharma Pharma isis phase developing aa LEDDS™-enabled LEDDS™-enabled formulation formulation of of developing the hydroxylase hydroxylase inhibitor inhibitor the dimethyloxaloylglycine (DMOG) (DMOG) to to bring bring about about dimethyloxaloylglycine effective, effective, safe safe and and targeted targeted delivery delivery of of this this potential potential therapeutic therapeutic agent. agent.

Dr Hugh Brady, UCD President presents PhD student Kate Byrne with the 2012 UCD Conway Festival gold medal, sponsored by Roche.

Conway collaborator scoopsofIrish TimesInteractions Innovation Award Hierarchical Model for Evolution Genetic Irishunprecedented biopharmaceutical development An comparison of the company,architecture Sigmoid Pharma recently scooped genetic of two organisms the overall Innovation of the Year award at separated by an estimated 400 million the inaugural Irish Times years of evolution has All-Island revealed global Innovation Awards. The life-science SME, trends that arguably exist in all founded by UCD pharmacology graduate, Dr eukaryotic species.

Ivan Coulter, has actively collaborated with

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

results in both academicpombe; outputs aand the Schizosaccharomyces fission application toward product yeast that of in research many ways (e.g.clinical splicing, development with indigenous companies.”

RNAi machinery) is more similar to metazoans S. cerevisae.This Commenting onthan the Taylor collaboration, Dr provided phenotypic signatures Coulter said, “The collaboration withfor the60% Taylor of the nonessential S. pombe the genes and laboratory clearly demonstrates potential that can befunction realised to through focused assigned 144 previously studies in humans have shown that non application of basicgenes research.

The development uncharacterised including mRNA studies in humans have shown non progression was damage associated withthat gross of a smart will depend on like-minded splicing &economy DNA checkpoint collaborative partners identifying progression was associated withopportunities gross deletions in the nef gene. factors.

tract is lined with cellsdiseases.” that block the of complex human saidcontents author of the gut from leaking into the intestine. In an Colm J. Ryan.

IBD patient, this barrier is broken and the contents of the gut leak out into surrounding “We hope that conserved trends areas. The research team in UCD Conway used identified in both species may be used a model of IBD and, by applying a new class of as guidelines improve the search were for drugs known asto hydroxylase inhibitors, epistasis in genome wide association able to almost completely reverse the of HIV nef arealso critical the rate studies and for in thedetermining rational design symptoms of the disease.

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

Meta-analysisofbythe UCD researchers led by The international sincefindings being granted a Science Foundation Meta-analysis UCD researchers led byhas Conway Fellow,byProfessor Denis Shields collaboration included Conway Ireland industrythat research partnership award Conway Fellow, Shields has determined that Professor there is noDenis clear evidence Fellow, Gerard Cagney; Professor in 2004.Dr that particular viral sequences in determined thatdefective there isand no Dr clear evidence Padraig Cunningham Derek Greene, The Irish Times award recognises the stellar the HIV-1 nef of gene or certain regions that particular defective sequences inin UCD School Computer Science &of the innovative performance ofviral Sigmoid Pharma protein play significant role indevelopment. disease the HIV-1 nefaand gene or certain regions ofJ. the Informatics; student Colm Ryan their application of PhD research and progression. protein play ahas significant role in disease were published indeveloped Molecular Cell.

Genetic, The company two new drug technologies, LEDDS™ and report SmPill™, not progression. or epistatic,patients interactions onwhich HIV-infected can be categorised on only enhance the solubility and permeability of functional dependencies between genes. the basisbut of the number oftoyears it takes for HIV-infected patients can categorised on the drug can deliver itbe targeted locations They can be used to describe the crossthem to progress to AIDS. Some in the gastrointestinal tract, including the for the basis of thepathways number ofand years itpatients takes talk between processes maintain stable CD4 lymphocyte counts colon. them toreveal progress to groups AIDS. Some patientsand and to how of proteins and do not go on to develop AIDS even after more maintain stable CD4 lymphocyte counts and complexes work together to perform The Sigmoid Pharma-Taylor collaboration is than 10 years of infection. do not go on todevelopment develop AIDS higher level functions. facilitating thebiological of even a newafter more therapeutic approach for thewhy treatment of than 10 years of infection.

Scientists are curious as to these longinflammatory bowel (IBD) by bringing term, (LTNP) patients do not Untilnonnow,progressor the onlydisease genome wide genetic Scientists areresearch curious as to whydifferences these long-in together the methodology of for the interaction network available was develop AIDS. This may reflect Taylor group with the proprietary term, nonprogressor (LTNP) patientsitdo not Saccharomyces cerevisiae, making the host, viral genetics or environmental liquid/emulsion drugmay delivery system, develop AIDS. This reflect in difficult forcould scientists to compare the for factors that potentially bedifferences exploited LEDDS®, developed byor Sigmoid Pharma. the host, viral genetics environmental

evolution of genetic interactions across the treatment of the disease. factors that could potentially be exploited for Commenting on the award, Professor Taylor species.

Studies in are model organisms shown said, “We delighted for Drhave Coulter andthat his the treatment of the disease. infection with nef-deficient virus shows team and indeed it reflects well on our To address this, the research team an Studies in model organisms have shown attenuated course of infection and some that partnership.

Aakey driver of successful constructed genome scale, quantitative scientific research in 2010 is meaningful infection interaction with nef-deficient virus shows an genetic network for interaction of academia with industry that attenuated course of infection and some

and realising basic applied research deletions in the nefand gene.

However, much of the research in the area to synergies.

This collaboration, initiated through Comparison ofsupplement, thethetwo networks been based onresearch observational or case However, much of in theprovides area to adate SFI has research highlights the evidence for athan hierarchical model oforthe studies systematic potential that companies date hasrather beeninnovative basedrigorous, on indigenous observational case evolution of genetic interactions, with working with academia canwork realise.” scientific evaluation.

This by doctoral studies rather than rigorous, systematic

conservation highest within candidate Ravindra Pushker setprotein outdoctoral to scientific evaluation.

This by Taylor’s collaboration with work Sigmoid Pharma has complexes, lower within biological determine in asuccessful substantially larger sample set candidate Ravindra Pushker set out to certainly been by these metrics with processes, and lowest distinct ifdetermine anyco-authored association exists between between disease three publications tothe date in two in a substantially larger sample setof biological processes.

Despite large progression and particular amino acidin the the highest ranking scientific journals if any association exists between disease evolutionary distance and extensive differences or deletionsand within the nef gene. field, Gastroenterology Proceeding of the progression and particular amino acidboth rewiring of individual interactions, National Academy of Sciences, as well as the differences deletions within thenonef gene.of networks retain conserved features On a per patient basis, there was excess generation oforproprietary innovative products and display similar levels of functional LTNP patients with one or more defective nef and the creation of high-skilled jobs.

On a per patient basis, there was no excess of crosstalk biological processes sequencesbetween when compared to progressors.

LTNPthan patients with one design orin defective More 15,000 people Ireland and nef suggestive of general principles of While the high frequency ofmore amino acid millions of people worldwideto are living with the sequences when compared progressors. genetic interactions.“ replacement at particular residues is indicative symptoms IBD today.

Current therapeutic While theevolvement, high frequency of amino acid of rapid permutation options for this chronic debilitatingtesting disease are replacement at particular residues is indicative This analysis provides valuable insight showed thatwith residues with more replacements very limited surgery often being the only of rapid evolvement, permutation testing into the evolution of biological systems than expected were not statistically significant. viable option.

The Sigmoid product, currently showed residues with more replacements and alsothat has practical implications for the in a phase II clinical study, uniquely enables The researchers conclude that current data identification of epistasis in mammalian thandelivery expected not statistically significant. oral of were a powerful drug without providessystemic no evidence that individual systems, a phenomenon believedresidues to causing side-effects.

The researchers that current data account for partconclude of the missing heritability Under normal conditions, gastrointestinal provides no evidence thatthe individual residues

of genetic HIV nef progression. are critical in screens determining the rate of disease Professor of interaction inDenis

“When we applied these new drugs to our IBD of disease progression.

Professor Denis Shields believes that searches for modifiers of metazoans.” model, gutrates was tricked into focus thinking progression should now on that otheritof Shieldsthe believes that searches for modifiers was being deprived of oxygen. activated host and viral factors.

“Systematic evaluation progression rates should nowThis focus on other Reference protective pathways,ofwhich in bioinformatics turn prevented of large quantities data by host and viral factors.

“Systematic evaluation Ryan et al.

Hierarchical Modularity and the Evolution of the death of the cells that line the can beInteractomes just as important inby refuting Genetic across Species.

Molecular Cell 46, of large quantities of data bioinformatics gastrointestinal tract,” explained Professor hypotheses that are current in the literature, as 691-704, June 8, 2012. can be“Our just as important in data refuting Taylor. pre-clinical trial can now ithypotheses is in the discovering patterns”, he said. thatphase areunknown current in the literature, as inform next Sigmoid Pharma product development pipeline”. it is in discovering unknown patterns”, he said.

This research was funded through Science

and University College InFoundation addition toIreland the product that is currently in This research was funded through Science CellSigmoid Pharma is Dublin. phase II clinical studies, Foundation Ireland and University College Process Process developing a LEDDS™-enabled formulation of Dublin.

Gene Gene the hydroxylase inhibitor dimethyloxaloylglycine (DMOG) to bring about Complex safe and targeted delivery of this Complex effective, Reference:therapeutic agent. potential

Meta-analysis to test the association of HIV-1 nef amino acid differences and deletions with disease progression.

Reference: Ravindra Pushker, Jean-Marc Jacquē,ofDenis Shields.

Meta-analysis to test the association HIV-1C.nef amino Journal of Virology, 2010 p3644-3653 acid differences andApr deletions with disease progression.

Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields. conservation of epistatic interactions across species Journal of Virology, Apr 2010 p3644-3653

Depicting the conservation of epistatic interactions across species

Conway collaborator Irish Times Innovation Award EU Research Effort to Fight scoops Diabetes using Oral Nanomedicines

Success in development EU FP7 call successfully results in bothdelivering academic insulin outputsorally and theas an Irish European biopharmaceutical The Commission has awarded Success in EU FP7 call alternative application oftoresearch toward clinical product company, Sigmoid recently scooped insulin injections currently FP7 funding for a Pharma new research project thepart overall Innovation themore Year award at as of efforts to of find effective Conway researchers led by Dr. Tara the inaugural Irishdiseases Times All-Island treatments for such as diabetes.

development indigenous companies.” used daily bywith diabetic patients to manage disease (CKD)This and improve patient their disease. convenient andtreatment, safe Commenting on the Taylor collaboration, Dr Innovation Awards.

The SME, McMorrow and Professor have with of particular focus on CKD arising from disease (CKD) improve patient treatment, Conway researchers led life-science byMichael Dr. TaraRyan way takingand the drug would significantly Coulter said, “The collaboration with the founded byand UCD pharmacology graduate, Dras improve patient compliance with theirTaylor McMorrow Professor Michael have with particular focus on CKDThe arising from diabetes and hypertension. multiThe multi-disciplinary TRANSINT successfully secured €485,500 inRyan funding laboratory clearly demonstrates the potential Ivan Coulter, has actively collaborated with medication and improve the quality (oral nanomedicines) consortium diabetes and research hypertension.

The multidisciplinary consortium has 25 part of an overall award to the Systems successfully secured €485,500 in funding as that can be realised through focused Conway Professor Taylor of life of (16 patients with diabetes.

Two combines expertise in Chronic pharmaceutical disciplinary research consortium has 25 part of anFellow, overall award to Cormac the Systems partners universities, 9 industry partners) Biology towards Novel Kidney application of basic research.

The May 2010.qxd:Layout 1 copy 07/05/2010 13:12 partners Page 3 universities, since being granted a Science Foundation other unnamed peptides owneddevelopment large nanotechnology, biochemistry, (16 9 industry partners) Biology Novel Chronic Kidney from 15 countries and the project isby due to run Diseasetowards Diagnosis and Treatment (SysKid) of a smart economy will depend on like-minded pharmaceutical companies are isalso being Ireland industry research partnership award immunology, toxicology, biology and from 15 countries and the project due to run Disease Diagnosis andEuropean Treatment (SysKid) for five years. consortium under the Union FP7 collaborative partners identifying opportunities evaluated. in 2004. under physiology with the aim of developing for years. basic and applied research consortium the European Union FP7 andfive realising programme. novel nanocarriers torecognises orally deliver a range The UCD Conway team, including postdoctoral The Irish Times award the stellar programme. synergies.

This collaboration, initiated through The UCD Conway team,of including of peptides for the treatment of diabetes, With a total budget €11 million, the innovative performance ofwas Sigmoid Pharma Dr. Craig Slattery andpostdoctoral Dr. the Natalia Syskid (www.SysKid.eu) established to in aresearchers SFI research supplement, highlights obesity and pain.

TRANSINT project brings together researchers Dr. Craig and Natalia Syskid (www.SysKid.eu) was established to their application of research development.

Martin, will cellSlattery culture andDr. animal further our understanding ofand chronic kidney potential thatutilise innovative indigenous companies seventeen leading research Martin, will utilise cellEuropean culture and animal further our understanding of chronic The company has developed two newkidney drug working with academia can realise.” organisations and major pharmaceutical Diabetes is one of theand most devastating technologies, LEDDS™ SmPill™, which not industrial partners, including Sanofi and has diseases worldwide.

In 2011, were 366 Taylor’s collaboration with Sigmoid Pharma only enhance the solubility and there permeability of Roche million suffering diabetes certainlyPharma. been successful by these metrics with the drugpatients but can deliver it tofrom targeted locations globally and at leasttract, 4.6 million people three co-authored publications to date in two of in the gastrointestinal including the died from The TRANSINT project is led

by Professor the highest ranking scientific journals in the colon.the disease.

María José Alonso, University of Santiago field, Gastroenterology and Proceeding of the The Sigmoid Pharma-Taylor collaboration is (USC) and Conway Fellow, Professor cells,tissues tissues andfluids. fluids.

Glycomicsneeds needs thesupporting supporting framework TRANSINT researchers will useframework National Academy of Sciences, as well as the cells, and Glycomics the facilitating thewell-curated development of new a newways David Brayden is the deputy coordinator. of extensive, databases andof nanotechnology to explore generation of proprietary innovative products of extensive, well-curated databases and

tract is linedBrayden with cells that contents Professor and hisblock UCDthe research of the gut leaking theofintestine.

In an team willfrom provide oneinto type nanocarrier, IBD patient, this barrier and is broken andtransport the examine nanocarrier peptide modelsintestinal to processes involved contents of identify the guttissue leak out into surrounding across and use highin early CKD progression and novel areas.

The research team in UCD Conway used models toscreening identify processes involved in early content toinvestigate look at particle auptake model of for IBD and, applying anovel newthe class of strategies preventing and slowing CKD progression andby investigate and cytotoxicity. drugs known asthe hydroxylase inhibitors, strategies for of preventing and These slowing thewere progression disease. studies will able to almost completely reverse the“Thiswill progression of with the disease.

These studies be integrated clinical and epidemiological Professor Brayden commented: was symptoms ofgrant thethe disease. be integrated with clinical and as epidemiological astudies fantastic to secure we were able across consortium using systems studies across theSFI consortium using systemsnew to leverage the Irish Drug Delivery biology methodologies in order to develop “When we applied these new drugs to our IBD biology methodologies in order to develop new Network instrategies promoting three Irish partners, diagnostic and treatment options model, the gut was tricked into thinking that to it including UCC and and Sigmoid Pharma as diagnostic strategies treatment options to prevent CKD development.

Email was being deprived of oxygen.

This activated well as UCD. We will be working with prevent CKD development.

Email tara.mcmorrow@ucd.ie for in details of a PhD protective pathways, which turn prevented some of the best available. oralfor delivery tara.mcmorrow@ucd.ie detailsand of a ‘nano’ PhD position the death currently of the cells that line the groups in Europeavailable. and, because ‘big pharma’ position currently gastrointestinal tract,” explained Professor are involved, we have a real chance of Taylor.

“Our pre-clinical trial data can translating positive preclinical datanow to inform next phase Sigmoid Pharma product patientthe care.” development pipeline”.

GlycoExtractor advances advances glycan glycan data data manipulation manipulation GlycoExtractor

Commercialpackages packagesthat thatsupport supportHPLC HPLC therapeutic approach for the treatment Commercial flexible analytical tools.

Currently, thisoffield field and the creation of high-skilled jobs. flexible analytical tools.

Currently, this instrumentscannot cannotfacilitate facilitatethe theextraction extractionofof inflammatory disease (IBD) by bringing instruments of studylacks lacksbowel theestablished, established, of study the More than 15,000 people Ireland and largequantities quantities data.InIninan an effortto toalleviate alleviate together the research methodology of the large ofofdata. effort comprehensive andcentralised centralised data comprehensive and data millions of people worldwide are living with the this bottleneck within high-throughput Taylor group with the proprietary this bottleneck within high-throughput collections,standards standardsand andinformation information collections, symptoms IBD today. therapeutic glycomicprojects, projects, theCurrent NIBRTteam teamhave have liquid/emulsion drug delivery system, glycomic the NIBRT reporting protocolsthat thatexist existwithin within reporting protocols options this chronic tool debilitating disease results infor both academic outputs and the are Irish biopharmaceutical development An international consortium (GENIE) known.

The researchers carefully analysed LEDDS®, developed by Sigmoid Pharma. developed a web-based tool that interfaces developed a web-based that interfaces genomics genomicsand andproteomics. proteomics. very limited surgery often clinical being only application ofwith research product company, Sigmoid Pharma led by researchers at therecently UCD scooped over two million DNAtoward markers in the the with Waters chromatography software withthe the Waters chromatography software Commenting on the award, Professor Taylor viable option.

The indigenous Sigmoid product, currently Diabetes Centre for genome ofimprove each person with diabetes development with companies.” the overall Research Innovation of the Year award at Researchers, Dr Artemenko and package toto and the export package improve andautomate automate the export Researchers, DrNatalia NataliaCentre; Artemenko andDr Dr said, “We are delighted for Dr Coulter and his in adata phase II clinical uniquely enables Public Health, Queen’s University who participated instudy, the gene In the the inaugural Irish Times Matthew Campbell from the National Institute of totovarious file formats for subsequent ofdata various file formats forscan. subsequent Matthew from theAll-Island National Institute Commenting onof collaboration, Dr team andCampbell indeed it reflects well onofour oral delivery of athe powerful drug without Belfast; The Broad Institute MIT/ largest study itsTaylor kind, the investigators Innovation Awards.

The life-science SME, analysis.

The modular architecture ofofthe tool of Bioprocessing Research &&Training (NIBRT) of Bioprocessing Research Training (NIBRT) analysis.

The modular architecture the tool Coulter said, “Theside-effects. collaboration with the Taylor partnership.

A key driver of successful causing systemic Harvard and the University of Helsinki recruited 4,750 patients with diabetic founded by UCD pharmacology graduate, Dr led by Conway Fellow, Professor Pauline Rudd also facilitates the manipulation of data from led

by Conway Fellow, Professor Pauline Rudd also facilitates thedemonstrates manipulationthe of data from laboratory clearly potential scientific research in 2010 is meaningful has discovered genes associated with kidney disease and almost 7,000 patients Ivan developed Coulter, has collaborated with have an open access, web-based other data management systems. have developed anactively openwith access, web-based other data systems.

Under normal conditions, thefocused gastrointestinal that can be management realised through interaction of academia industry that risk of diabetic kidney disease. with long-standing diabetes but with no Conway Fellow, Professor Cormac Taylor interface that extraction, querying interface thatfacilitates facilitates extraction, querying application ofkidney basic research.

The to development The NIBRT team are now working evidence of disease. since beingofgranted a Science Foundation The NIBRT team are now working tointegrate integrate and sharing HPLC-glycan data generated in and sharing of HPLC-glycan data generated in of a smart economy willEUROCarbDB depend on like-minded with the Kidney disease is a common and serious Ireland industry research partnership award May 2010.qxd:Layout 1 processes. copy 07/05/2010 13:12 GlycoExtractor Page 3 GlycoExtractor with the EUROCarbDB high throughput high throughput processes. collaborative partners identifying opportunities framework to provide a comprehensive highcomplication of diabetes and it is Their findings, published in the journal in 2004. framework to provide a comprehensive highand realising basic andanalysis applied platform research for throughput HPLC data Glycosylation is theamost common and risk associated with increased PLoS Genetics, demonstrate that Glycosylation is award the greatly most common andstellar throughput HPLC data analysis platform for The Irish Times recognises the synergies.

This collaboration, initiated through structurally diverse post-translational the storage and annotation of experimental of heart attack and stroke.

Globally, changes associated with two genes; the storage andsupplement, annotation of experimental structurally diverse post-translational innovative performance of Sigmoid Pharma in a SFI research highlights the modification of proteins.

More than half of all data.

The integration of next generation diabetic kidney isDr. now the AFF3 and ERBB4, increase the risk of disease (CKD) and improve treatment, Conway researchers led by Tara data. The integration of indigenous nextpatient generation modification ofhave proteins.

More than half of all their products application ofdisease research and development. potential that innovative gene beenstage shown to be bioinformatic tools will the companies leading cause of end kidney failure kidney disease.

When the arising researchers McMorrow andhas Professor Michael Ryan have with particular focus onfurther CKD from The company developed two new drug gene products have been shown to be bioinformatic tools will further the working and withhypertension. academia canthe realise.” glycosylated.

With many specific glycans or as development of unified approaches forof these requiring dialysis or€485,500 kidney transplant. experimentally altered diabetes Thelevels multisuccessfully secured in funding technologies, LEDDS™ and SmPill™, which glycosylated.

With many specific glycans or not development of unified approaches for glycoforms showing potential asSystems cancer handling large scale glycomics data initiatives Meta-analysis by award UCD researchers led by studiesincollaboration in humans have shown that non genes kidney cells, they were able disciplinary research consortium has 25 to has part of an overall to the Taylor’s with Sigmoid Pharma only enhance the is solubility andaspermeability of glycoforms showing potential cancer handling large scale glycomics data initiatives with applications in biomarker discovery biomarkers, there an increasing need to has Conway Fellow, Professor Denis Shields progression was associated with gross mimic disease. partners (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney Up to now scientists and clinicians were certainly been successful by these metrics with the drug but can deliver it to targeted locations biomarkers, there is an increasing need to with applications in biomarker discovery develop high throughput, highly sensitive and determined that there no clear evidence deletions in the nef gene. from 15 countries the project is due runof Disease Diagnosis andisTreatment (SysKid) aware that only some patients with three co-authored publications to date into two This research was and partially supported by in the gastrointestinal tract, including theofand develop high throughput, highly sensitive robust strategies that the glycome that particular defective viral sequences in for five years. consortium under thedetail European Union FP7 diabetes will develop kidney disease but Conway Fellow and lead investigator This research was partially supported by the highest ranking scientific journals in the colon. strategies that detail the glycome of However, much of the research in the area to robust programme. the HIV-1 genesusceptibility or certain regions of the the basis nef of this was not of theGastroenterology UCD group, Professor Catherine field, Proceeding of case the The team, including postdoctoral dateUCD has Conway been based onand observational or protein play aPharma-Taylor significant role in disease is The Sigmoid collaboration National Academy ofrigorous, Sciences, as Dr. wellNatalia as the researchers Dr. than Craig Slattery and Syskid (www.SysKid.eu) was established to studies rather systematic progression. facilitating development a new kidney generation of proprietary innovative products Martin, willevaluation. utilise cellThis culture and further our the understanding of of chronic scientific work byanimal doctoral therapeutic approach for the treatment of and the creation of high-skilled HIV-infected patients can be categorised on candidate Ravindra Pushker setjobs. out to inflammatory bowel disease (IBD) by bringing the basis of the number of years it takes for determine in a substantially larger sample More than 15,000 people in Ireland and set together the research methodology of the them to progress to AIDS. Some patients if any association exists between disease millions of people worldwide are living with the Taylor group with the proprietary maintain stableled CD4 counts progression and particular most likely to die as a Current resultamino oftherapeutic the acid raised New research by lymphocyte Conway Fellow Dr and symptoms IBD today. liquid/emulsion drug delivery system, do not goKennedy on toled develop AIDSthat even after differences or seen deletions withinofthe gene.are glucose levels Breandán indicates treatment most likely to die asinadiabetes. result thenef raised New research by Conway Fellow Dr more options for this chronic debilitating disease LEDDS®, developed by Sigmoid Pharma. than 10 years of infection. of diabetic blindness should look at glucose levels seen in diabetes.

Breandán Kennedy indicates that treatment very limited with surgery often being the cells, tissues and fluids.

Glycomics needs the supporting framework OnKennedy a per patient basis, there was nonew excess of Dr andacademic his team found that blood results instudies both outputs and the only Irish biopharmaceutical development Several have provided strong New research by award, anshould international protecting the neurons responsible colour Commenting on the Professor Taylor of extensive, well-curated databases and of diabetic blindness look atforscooped viable option.

The Sigmoid product, currently Scientists are curious as to why these longLTNP patients with one or more defective nef vessels and the neuronal cell death in diabetic application of research toward clinical product company, Sigmoid Pharma recently Commercial packages that support HPLC evidence that calcium plays a crucial team of scientists including UCD Dr Kennedy and his team found that new blood vision in the eye and not just targeting the said, “We are delighted for Dr Coulter and his flexible analytical tools.

Currently, this field in a phase IIcan clinical study, uniquely enables protecting the neurons responsible fordo colour term, nonprogressor (LTNP) patients not sequences when compared to progressors. retinopathy arise independently of development with indigenous companies.” the overall Innovation of the Year award at instruments facilitate the extraction of role in regulating protein translation and Conway’s Drthe O’Connell provides vessels andcannot the neuronal cell death in each diabetic blood vessels asDavid is currently the team and indeed itand reflects well onpractice. our of study established, oral delivery of afrequency powerful drug without vision inlacks the eye notreflect just targeting thein develop AIDS. This may differences While high of amino acid other.

Inthe addition, they identified that cone the inaugural Irish Times All-Island large quantities of data.

In an effort to alleviate indeed that CaM antagongists block the strong evidence that calmodulin partnership. A key of successful retinopathy can arise independently of each comprehensive anddriver centralised data Commenting on the Taylor collaboration, Dr causing systemic side-effects. blood vessels as people is currently the practice. the host, viral genetics orworldwide environmental replacement at particular residues is indicative photoreceptor neurons, those involved in Nearly 2.5 million areSME, blind this bottleneck within high-throughput Innovation Awards. life-science initiation of “The protein interacts directly with functional collections, standards and information scientific research inThe 2010 is meaningful other. Insaid, addition, theysynthesis. identified that cone Coulter collaboration with the Taylor glycomic projects, thepermutation NIBRT team have factors that could potentially be exploited for of rapid evolvement, testing colour vision and used in daylight, are most due to diabetic retinopathy.

This secondary founded by UCD pharmacology graduate, Dr ribosomes and plays an important role reporting protocols that exist within Under normal conditions, the gastrointestinal interaction of academia with industry that photoreceptor neurons, those involved in Nearly 2.5 million people worldwide are blind laboratory demonstrates the potential developed aclearly web-based tool that interfaces thethe treatment of the disease. showed that residues with more replacements affected by the high glucose levels. complication diabetes activates the growth Ivan Coulter, actively collaborated withof genomics andofhas proteomics. in calcium dependent regulation Protein translation takes place at the colour vision and used daylight, are most due to leaky diabetic retinopathy.

This that can be realised through focused with the Waters chromatography software than expected were not in statistically significant. of new blood vessels inCormac the secondary eyeTaylor and is Conway Fellow, Professor protein 80S ribosome, which consists of Studies insynthesis. model organisms have shown The research team made theirlevels. observations Researchers, Dr Natalia Artemenko andgrowth Drthat package to and automate thetwo export application of basic research.

The development affected byimprove the high glucose complication ofthe diabetes activates the responsible death of photoreceptors, since beingfor granted a Science Foundation smaller subunits: 40S and In this infection withblood nef-deficient anis The researchers conclude that60S. data Matthew Campbell from the virus National of data various file formats for subsequent using a to novel zebrafish model ofcurrent diabetes, of a smart economy will depend on like-minded of new leaky vessels in theshows eyeInstitute and the neurons that send visual messages to our Ireland industry research partnership award study, the analysed theobservations interaction Calmodulin (CaM)is a calcium The research team made analysis.

The modular architecture ofdiabetic the tool of Bioprocessing Research &photoreceptors, Training (NIBRT) provides noteam evidence thattheir individual residues attenuated course ofdeath infection and binding some which resembles the early stages of collaborative partners identifying opportunities responsible for the of brain. in 2004. of CaM with purified 80S ribosomes and protein that is highly conserved within using a novel zebrafish model of led by Conway Fellow, Professor Pauline Rudd also facilitates the manipulation ofdiabetes, data from retinopathy inbasic humans. is an exciting and realising and Itapplied research the neurons organisms. that send visual messagesto to our polyribosomes using surface plasmon eukaryotic Inthe response have developed an openrecognises access, web-based other data management systems.

The Irish Times award the stellar which resembles the early stages of diabetic development for the group who now hope to Until now, it was unclear if changes to synergies. This collaboration, initiated through brain. interface that facilitates extraction, querying resonance technology.According totheDra intracellular calcium level changes, CaMin innovative performance of Sigmoid Pharma intheir humans.

Itworking ishighlights an exciting further extend research and establish vessels and neurons occurred independently of aretinopathy SFINIBRT research supplement, The team are now to integrate and HPLC-glycan data generated O’Connell, “We identified putative CaMto regulates large number of changes proteins theirsharing application of research and development. development for the group who nowcompanies hope Until now,and itaofwas unclear if the toinisin model of late diabetic disease. one other which type of retinal neuron potential that stage innovative indigenous GlycoExtractor with the EUROCarbDB high throughput processes. many signalling pathways.

The company has two newled drug framework to academia provide a comprehensive further extend theirhave research andthat establish vessels and neurons occurred independently Meta-analysis by developed UCD researchers by of studies in humans shown nonhigh-a working with can realise.” technologies, and SmPill™, whichhas Glycosylation the most common and throughput HPLC data analysis platform Conway Professor progression was associated with gross for model of late stage diabetic disease. one otherFellow, andisLEDDS™ which type ofDenis retinalShields neuron isnot Taylor’s collaboration with Sigmoid Pharma has only enhance the there solubility permeability structurally diverse post-translational the storage of experimental determined that is noand clear evidence of deletions inand the annotation nef gene. certainly successful by generation these metrics with modification proteins. than halflocations of in all data.

The been integration of next the butof can deliver More itviral to targeted thatdrug particular defective sequences bioinformatic tools will further the gene products have been shown to be However, much ofpublications the research the area to of three co-authored toindate in two in gastrointestinal including thethe HIV-1 nef gene or tract, certain regionsthe of the glycosylated. With many specific glycans or development ofbased unifiedonapproaches for or case date has been observational

In addition to the product that is currently in phase II clinical studies, Sigmoid Pharma is EUROCarbDB, researchinfrastructure infrastructure design developing a LEDDS™-enabled formulation of EUROCarbDB, aaresearch design study fundedbybyinhibitor theEU EU6th 6thFramework Framework the hydroxylase study funded the Programme.Prospective Prospective userscan can access the dimethyloxaloylglycine (DMOG) to bring about Programme. users access the GlycoExtractor tool on effective, safe and targeted delivery of this GlycoExtractor tool on potential therapeutic agent. http://glycobase.nibrt.ie:8080/DemoGlycoExtra http://glycobase.nibrt.ie:8080/DemoGlycoExtra ctor/mainPage. ctor/mainPage.

Conway collaborator Times Innovation New Genes Associated with scoops DiabeticIrish Nephropathy Risk Award

Success in EU FP7 call

Reference Reference tract is lined with cells that block the contents Godson said, “These new research GlycoExtractor: web-basedinterface interfacefor forhigh high GlycoExtractor:AAweb-based of the gut from leaking into the intestine. findings are very important as they In an throughput processing of HPLC-Glycan data throughput processing of HPLC-Glycan data define that underpin IBD patient, this barrier isP.broken and the V.V.mechanisms Artemenko, Matthew and Pauline Natalia Natalia Artemenko, Matthew P.Campbell, Campbell, and Pauline M. Journal Proteome Research, 2010, the development of this devastating contents of theofof gut leak out into surrounding M.Rudd Rudd Journal Proteome Research, 2010,9 9(4), (4),pppp 2037–2041 2037–2041 disease. research accelerate areas.

TheThis research teamhelps in UCD Conway used new and effective adevelopment of model of IBD and, by applying a new class of therapies”. drugs known as hydroxylase inhibitors, were able to almost completely reverse the This work of is the supported symptoms disease. by the US-Ireland

research and development programme,

“When we appliedinitiative these newfunded drugs to a collaborative byour IBD model, gut was tricked into thinking that it SciencetheFoundation Ireland, the Northern was being deprived of and oxygen. activated Ireland R&D Office the This US National protective pathways, which in turn prevented Institutes of Health. models to identify processes involved in early the death of the cells that line the CKD progression and investigate novel gastrointestinal tract,” explained Professor strategies for preventing and slowing the Taylor. pre-clinical data can now of HIV“Our nef are critical intrial determining the rate progression of the disease.

These studies will Reference inform the next phase Sigmoid Pharma product be withSusceptibility clinical Professor andLoci epidemiological ofintegrated disease progression.

Denis Sandholm et al.

New Associated with NIBRT researchers Dr that Matthew Campbell and Dr Natalia development studies across the consortium using systems Shields believes searches for modifiers Kidney Disease inpipeline”.

Type 1 Diabetes.

PLoS Genetics 8(9): of Artemenko who developed GlycoExtractor NIBRT researchers Dr Matthew Campbell and Dr Natalia biology methodologies in order to develop new e1002921 doi:10.1371/journal.pgen.1002921 September progression should nowisfocus on other In addition to rates the product that currently into Artemenko who developed GlycoExtractor diagnostic strategies and treatment options 2012 host and viral factors.

“Systematic evaluation phase IICKD clinical studies, Sigmoid Pharma is prevent development. of large quantities of data Email by bioinformatics developing a LEDDS™-enabled formulation tara.mcmorrow@ucd.ie for details of a PhD of can be just as important in refuting the hydroxylase position currentlyinhibitor available. hypotheses that are current in the literature, dimethyloxaloylglycine (DMOG) to bring aboutas it is in discovering unknown patterns”, he said. effective, safe and targeted delivery of this

Bioinformatic analysis of HIV progression studies

Zebrafish model gives insights into diabetic blindness Zebrafish model gives insights into diabetic blindness potential therapeutic agent.through Science This research was funded Conway collaborator Irish Times Innovation Award Regulating Protein Synthesis GlycoExtractor advances glycanscoops data manipulation Foundation Ireland University College Commenting on the and research, Dr Kennedy Dublin. said, “By establishing a robust model for early Commenting on the research, Dr Kennedy

and late stage diabetic retinopathy, we would said, establishing a robust for early EUROCarbDB, a research infrastructure design tract is“By lined cells previously that blockmodel the contents binding siteswith inthe two identified hope to better understand the progression of study funded by EUinto 6th Framework and late stage diabetic retinopathy, we would of the gut from leaking the intestine.

In an ribosomal CaM targets andfor synthesised the disease and pave the way identifying Programme.

Prospective users can access the hope to better understand the progression IBD patient, this barrier is broken and thea of these as linear peptides.

Then, using GlycoExtractor tool new targets foronitsthe successful treatment”.

Reference: the drug disease andgut pave identifying contents ofinthe leak outway intofor surrounding cell-free, translation we http://glycobase.nibrt.ie:8080/DemoGlycoExtra Meta-analysis tovitro test the association ofsystem, HIV-1 nef amino areas.

The research team in UCD Conway new drug targets for its successful treatment”. found thesewas synthetic to be used The funded peptides through Science acid research differences and deletions with disease progression. ctor/mainPage.

aFoundation model inhibitors of IBD and, byprotein applying a Research new Ravindra Pushker, Jean-Marc Jacquē, Denis C. class Shields.of potent of synthesis”.

Ireland and the Health Reference The research was through Science Journal of Virology, Aprfunded 2010interface p3644-3653 drugs known hydroxylase inhibitors, GlycoExtractor: Aas web-based for high were Board. processing ofand HPLC-Glycan data throughput Foundation Ireland the Health Research able to almost completely reverse the Natalia V. Artemenko, Matthew P. Campbell, and Pauline Board. of the disease. symptoms M. Rudd Journal of Proteome Research, 2010, 9 (4), pp Reference Reference: 2037–2041

“When these newInteraction drugs to our IBD Behnen etwe al. applied Calcium-Dependent Predominant cone photoreceptor dysfunction ofReference: Calmodulin withwas Human 80S Ribosomes andin athat it model, the gut tricked into thinking hyperglycaemic model of non-proliferative diabetic Polyribosomes.

Biochemistry 2012, 51, 6718-6727 was being Yolanda deprived of oxygen.

This activated retinopathy.

Alvarez, Jenneth Chen, Alison Predominant cone photoreceptor dysfunction in a doi:10.1021/bi3005939 protective pathways, turn prevented Reynolds, Nore Waghorne, John J.inO’Connor, Breandan hyperglycaemic model ofwhich non-proliferative diabetic Kennedy.

Disease Models & Mechanisms (2010) the death of the cells that line the retinopathy. Yolanda Alvarez, Jenneth Chen, Alison of HIV nefNore areWaghorne, critical determining the rate gastrointestinal tract,” in explained Professor Reynolds, John J. O’Connor, Breandan of disease progression.

Professor Denis Taylor.

“Our pre-clinical data can now Kennedy.

Disease Models & trial Mechanisms (2010) Shieldsthe believes that searches for modifiers of inform next phase Sigmoid Pharma product progression pipeline”. rates should now focus on other development host and viral factors. “Systematic evaluation

Bioinformatic analysis of HIV progression studies