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lower iNKT cells in comparison to lean and after commencing treatment; an Centre of Excellence hosts international workshop individuals. increased number in the circulation and

May

UCD clinician scientists and Irish biopharmaceutical development researchers fromPharma NUI Maynooth and company, Sigmoid recently scooped the overall Innovation of the Year award at Trinity College led by Conway Fellow, the inaugural Irish O’Shea Times All-Island Professor Donal have reported Innovation Awards. The life-science SME, an improvement in the severity founded by UCDCentre pharmacology graduate, As a European of Excellence, the Dr of psoriasis in patients following with Ivan Coulter, has actively collaborated Department of Rheumatology in St Vincent’s glucagon-like (GLP-1) Conway Fellow, peptide-1 Professor Cormac Taylor University Hospital chosen to host an since beingtherapy. granted was aTheir Science Foundation analogue findings, international workshop on March Ireland industry research partnership award published intwo-day Diabetologia raise the in 2004. 26th & 27th of 2010. Sponsoredapplications by Roche possibility therapeutic The Irish Times award recognises the stellar Pharma, the workshop gave for GLP-1 in1Participate inflammatory conditions 2010.qxd:Layout copy of07/05/2010 innovative performance Sigmoid Pharma 13:12 in due to the direct impact on innate twenty rheumatologists from centres in their application of research and development. natural killer T (iNKT) cells. Europe and Australia the opportunity to The company has developed two new drug technologies, LEDDS™ and SmPill™, which not witness the care of patients with rheumatoid only enhance solubility and permeability of Psoriasis is anthe skin arthritis (RA) atinflammatory St Vincent’s. the drug but can deliver it to itching, targeted locations condition causing scaling, in the gastrointestinal tract, including the redness and plaque formation to varying colon.

degrees of severity. Associated with obesity and Pharma-Taylor other metabolic diseases is The Sigmoid collaboration facilitating the development such as diabetes, it carriesofana new increased therapeutic approach fordisease. the treatment risk of cardiovascular iNKT of inflammatory bowel disease by bringing cells are implicated in the (IBD) development together the research methodology of the of psoriasis and obese people have

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

The clinical team St Vincent’s Commenting on the based Taylor in collaboration, Dr University found anwith unexpected Coulter said,Hospital “The collaboration the Taylor The Participate in programme focused on improvement the severity of psoriasis laboratory clearly demonstrates the potential regimens for RAwithin in the that be treatment realised through focused inadvanced a can patient with type 2 diabetes clinic,ofincluding practical aspects oftherapy. biologic application of basic research. The development days starting GLP-1 analogue therapy carried out the accredited infusion of a smart economy will depend like-minded They surmised thisin was due toonthe direct collaborative partners identifying opportunities suite that provides care for RA action of GLP-1 onoptimal iNKT cells. and realising basic and patients. In addition to applied lecturesresearch from Conway synergies. This collaboration, initiated through Page 3 Fellows, Professors Oliver FitzGerald and The team began treating two obese a SFI research supplement, highlights the patients withinnovative type 2 diabetes andcompanies Douglas that Veale, delegates heard from clinical potential indigenous psoriasis with theabout GLP-1 analogue, nurse specialists patient education, working with academia can realise.”

liraglutide. Both patientsofexperienced screening and monitoring biological Taylor’s collaboration with Sigmoid Pharma has relief from their psoriasis symptoms therapies. certainly beenof successful these metrics with within days starting by treatment and the three co-authored publications to date in two of psoriasis area and severity index (PASI) the highest ranking scientific journals in the decreased in both. field, Gastroenterology and Proceeding of the

National Academy of Sciences, as well as the Describingofthe laboratory findings, Dr. generation proprietary innovative products Andrew E. Hogan, UCD Newman and the creation of high-skilled jobs. Scholar

tract is lined with cells that block the contents of the gut from leaking into the intestine. In an IBD patient, this barrierinispsoriatic broken and the decreased number plaques. contents the gut leakiNKT out into surrounding We alsooffound that cells expressed areas. researchand team in UCD Conway used GLP-1The receptor modulated cytokine aproduction”. model of IBD by applying a newMs class of Addressing theand, international guests, Mary drugs asof hydroxylase inhibitors, Duff,known Director Nursing and Ms. Kay were able to almost completely reverse the Connolly, Assistant Directorbelieves of Nursing Professor O’Shea thatfor the symptoms ofDonal the disease.

Bone & Joint Unit expressed their hope “Although extensive research will be that

“When we applied new drugs to our IBD required to investigate GLP-1 immune the experience ofthese the multidisciplinary team model, the gut was tricked into thinking thatfor it cell interactions, the potential benefit from St Vincent’s would provide a template for was being deprived of oxygen.such Thisas activated inflammatory conditions psoriasis delegatespathways, to reproduce similar care and protective which in turn prevented isfacilities promising”. the death of that line the forthe thecells management of RA patients in Reference: gastrointestinal explained Professor their respectivetract,” countries. Hogan “Our AE et al. Glucagon-like Taylor. pre-clinical trialpeptide-1 data can(GLP-1) now and thethe regulation of human invariant naturalproduct killer inform next phase Sigmoid Pharma T cells: lessonspipeline”. from obesity, diabetes and psoriasis. development Diabetologia (2011) 54:2745–2754 doi:10.1007/ Ins00125-011-2232-3 addition to the product that is currently in phase II clinical studies, Sigmoid Pharma is developing LEDDS™-enabled formulation Drucker DJ &a Rosen CF. Glucagon-like peptide-1 of the hydroxylase inhibitorobesity and psoriasis: (GLP-1) receptor agonists, dimethyloxaloylglycine (DMOG) to bring about diabetes meets dermatology. Diabetologia (2011) 54:2741–2744 effective, safe DOI and 10.1007/s00125-011-2297-z targeted delivery of this potential therapeutic agent.

Frog peptide structure selected for journal cover

Taylor group with the proprietary liquid/emulsion An image of thedrug frogdelivery peptidesystem, structure central LEDDS®, developed Sigmoid Pharma.team to the work of a UCDbyConway research

and senior scientist said, “There was an

More than 15,000 people in Irelandbefore and alteration in iNKT cell number millions of people worldwide are living with the symptoms IBD today.inCurrent variety of solutions order totherapeutic understand the options for this chronic debilitating disease are structural basis for the difference in biological very limited with surgery often being the only activity. viable option. The Sigmoid product, currently in a phase II clinical study, uniquely enables Thisdelivery particular peptide, isolated from the oral of academic aXT-7 powerful drug without results in both and the overexpressed in EOC outputs and their impact skin of systemic Silurana tropicalis, shows potential for causing side-effects. application of research toward clinical product on chemoresistance. drug development as it has impressive activity development with indigenous companies.” Under normal conditions, the gastrointestinal

collaborator IrishAwards Times Innovation Award Conway Conway Successes at SSRA scoops and MGA

was selectedon asthe theaward, front cover image for the Commenting Professor Taylor said, delighted forscientific Dr Coulter and his April “We 2010are edition of the journal, team and indeed it reflects well our Biochimica Actaon (BBA); Irish biopharmaceutical More than et 10Biophysica Conwaydevelopment Fellows partnership. A key driver of successful Proteins &Sigmoid Proteomics. company, Pharma recently scooped supervised undergraduate medical scientific research in 2010 is meaningful the overallfor Innovation of theor Year award at students laboratory clinical interaction ofthe academia with industry that Peptides in skin of many species of frog the inaugural Irish Times All-Island research projects during the summer. have anti-bacterial and anti-fungal properties Innovation Awards. The life-science SME, as The students presented their results May 2010.qxd:Layout 1ability copy 07/05/2010 13:12 founded bythe UCD pharmacology graduate, Dr as well as to student lyse or rupture part of the summer research Ivan Coulter,cells. has actively collaborated with mammalian This innate immunity by awards (SSRA) scheme organised Conway Fellow, Professor Cormac Taylor protects it fromofattack. These&properties UCD School Medicine Medicalof since being granted a Science Foundation frog skinindustry peptides are exciting from theaward Science. Ireland research partnership prospect in 2004. of being developed into

against the growth bacteria and Medical Candida Dr Len Harty the UCD Commenting onreceived the of Taylor collaboration, Dr albicans. However, this potential as an Graduate Association (MGA) O’Connell Coulter said, “The collaboration with theantiTaylor Page 3 laboratory clearly thehaemolytic potential Research Medal for his work entitled infective agent is demonstrates restricted by its that canTNF be realised through focused “Early Inhibition Therapy Greatly activity. application of basic research. The development Reduces the Impact of Inflammatory of smarton economy willProductivity depend on like-minded Arthritis over A achange to Personal the amino acid structure of the collaborative partners identifying opportunities Time”. Len works with Professor XT-7 peptide can create an analogueDoug that and realisingDr basic and Fearon applied in research Veale Ursula thewithout the retainsand anti-infective properties but synergies. This collaboration, initiated through studies in humans have shown that non Education Research Centre, St Vincent’s aprogression SFI research supplement, highlights complicating haemolytic activity. The the single was associated with gross University Hospital. His study of early potential that innovative indigenous companies deletions in substitution the nef gene. amino acid (glycine replaced by arthritis patients suggests that the working with academia can realise.” lysine) improves therapeutic potential However, ofthe the research the area of to impact ofmuch arthritis on patientinproductivity Taylor’s with Sigmoid has date has been occurring based on observational or case this naturally peptide. may becollaboration used as a predictor whenPharma certainly beenearly successful by these metrics with studies rather than TNFi rigorous, systematic considering therapy. three co-authored publications in two of scientific evaluation. This workto bydate doctoral the highestRavindra ranking scientific journals candidate Pushker set out toin the field, Gastroenterology and Proceeding of the determine in a substantially larger sample set National Academy exists of Sciences, as disease well as the if any association between generation ofand proprietary innovative products progression particular amino acid and the creation of high-skilled jobs. differences or deletions within the nef gene.

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.

Bioinformatic analysis of HIV progression studies

therapeutically valuable anti-infective and antiValerie received the Research The IrishToh Times award recognises theled stellar Meta-analysis by UCD researchers by Excellence Silver medal her project cancer agents. innovative performance of for Sigmoid Pharmahas in Conway Fellow, Professor Denis Shields entitled, “The Fate ofisChemoresistance their application of research and development. determined that there no clear evidence Conway Fellow, Drdeveloped Chandralal Hewage and his in Epithelial Ovarian Carcinoma (EOC)”. The company has new drug that defective viraltwo sequences in teamparticular carried out molecular modelling of the technologies, and SmPill™, which Jointly supervised bycertain Dr Amanda McCann the HIV-1 nef LEDDS™ gene or regions of thenot only enhance the solubility and[G4K]XT-7 permeability XT-7Dr peptide its analogue a and Fionaaand Furlong, Valerie looked protein play significant role in diseaseatin of the drug but canregulation deliver it to of targeted locations the epigenetic two proteins progression. in the gastrointestinal tract, including the HIV-infected patients can be categorised on colon. the basis of the number of years it takes for The Sigmoid Pharma-Taylor collaboration them to progress to AIDS. Some patients is facilitating the development of a new maintain stable CD4 lymphocyte counts and therapeutic approach for AIDS the treatment do not go on to develop even afterofmore inflammatory disease (IBD) by bringing than 10 years bowel of infection. Irish biopharmaceutical development together the research Nicole methodology the UCD researchers, Howeofand Scientists are curious asled to why thesescooped long-J. company, Sigmoid Pharma recently Taylor group with the proprietary Mariangela Ceruso, by Professor A new fortnightly forum for Conway graduate term, non- progressor (LTNP) patients do at not the overall Innovation of the system, Year award liquid/emulsion drug delivery Paul G. Malthouse recently published and postdoctoral researchers will be launched develop AIDS. This Times may reflect differences the inaugural Irish All-Island LEDDS®, developed by Sigmoid Pharma. in findings in Biochimia et Biophysica in May This initiative will give earlythe host,2010. viral genetics environmental Innovation Awards. Theorlife-science SME, Commenting on the award, Professor Taylor Acta Proteins & Proteomics on factors that could potentially be exploited for founded by UCD pharmacology graduate, Dr stage (BBA) researchers the opportunity to talk about said, “We are delighted for Dr Coulter and his the treatment of the disease. Ivan Coulter, has actively collaborated their investigation of the pH stability science and issues that concern them inwith an team and indeed it reflects well on our Conway Fellow, Professor Cormac domain Taylor of the stromelysin-1 catalytic informal with Studies inenvironment model have shown that partnership. A keyorganisms driver of refreshments successful since being granted a Science Foundation and its mechanism of interaction provided! Content for the forum will be an infection with nef-deficient virus shows scientific researchresearch in 2010 partnership is meaningful Ireland industry award attenuated course of infection and some interaction of academia with using industry that with a glyoxal inhibitor nuclear in 2004.

“When we applied these new drugs to our IBD model, the gut was tricked into thinking that it was being of oxygen. This activated of HIV nefdeprived are critical in determining the rate protective which in turn prevented of diseasepathways, progression. Professor Denis the deathat of cells that line the Pictured thethe SSRA ceremony (L-R) Mary Anne Kenny Shields believes that searches for modifiers of (Irish Medical Times), Valerie Toh (Research Excellance gastrointestinal tract,” explained Professor progression rates should now focus on other Coverand of April 2010 edition“Systematic of Biochimica etChair, Biophysica Silver awardee), Professor Michael Keane, Taylor. “Our pre-clinical trial data canevaluation now host viral factors. Acta (BBA); Proteins & Proteomics. research adjudication panel inform the next phase Sigmoid Pharma product of large quantities of data by bioinformatics development pipeline”. can be just as important in refuting hypotheses that are current in the literature, as In addition to the product that is currently in it is in discovering unknown patterns”, he said. phase II clinical studies, Sigmoid Pharma is developing a LEDDS™-enabled formulation This research was funded through Science of the hydroxylase inhibitor Foundation Ireland and University College dimethyloxaloylglycine (DMOG) to bring about Dublin. effective, safe and targeted delivery of this tract is lined with cells that block contents is oxyanion stabilisation and the 1H NMR potential therapeutic agent. oftothe gut from intoof thelow intestine. detect theleaking presence barrierIn an (thomas.scharzl@ucd.ie ) and postdoctoral IBD patient, bonds, this barrier is concluded broken and the hydrogen they that researchers, David Reference: contents of theDr gut leak Gomez out into surrounding Meta-analysis to test the association HIV-1 nef amino the inhibitor glyoxal group notSlattery directly (david.gomez@ucd.ie) and Drofis Craig areas. The research team in UCD Conway used acid differences and deletions with disease progression. coordinated the atom of aRavindra model Pushker, of IBD to and, bycatalytic applying azinc new of (craig.slattery@ucd.ie ) Jacquē, invite suggestions for Jean-Marc Denis C. class Shields. drugs known as PRTLI4 hydroxylase inhibitors, werethis the SCD. SFI, UCD funded Journal of Virology, Apr 2010and p3644-3653 the forum schedule. able to almost completely reverse the research. symptoms of the disease.

Irish Times Profiling Enzyme Active Sitescoops Characteristics Launch ofConway Conwaycollaborator postdoctoral & graduate forumInnovation Award

magnetic resonance (NMR) studies. The Irish Times award recognises the stellar

innovative performance of Sigmoid Pharma in

The are metalloproteases their stromelysins application of research and development. The company has developed twohave new similar drug and, as all metalloproteases technologies, LEDDS™ SmPill™, active sites, the teamand believe thatwhich their not only enhance the solubility and permeability of findings should provide insights into the drug but can deliver it to targeted locations

More than 15,000 people in Ireland On ainteraction per basis, there was and noand excess results in patient both academic outputs thewithof the of glyoxal inhibitors millions of people are livingproduct withnef the LTNPcatalytic patients withworldwide onetoward or more defective application of research clinical the domains of other similar decided by the members but it is envisaged symptoms today. Current therapeutic sequences IBD when compared tocompanies.” progressors. development with indigenous metalloproteases. that itthe will include a mixdebilitating of options forhigh this frequency chronic disease are While of technology amino acid Commenting onparticular the Taylor collaboration, Dr overviews, informal and often formal research very limited with surgery being the only replacement at residues is indicative Coulter said, “The collaboration with the viable option. Sigmoid product, currently In advance ofThe their experiments, theTaylor of rapid evolvement, permutation testing seminars, PhD viva rehearsals and career laboratory clearly the potential in a phase II clinical study, uniquely enables showed that residues with moreand replacements team looked at demonstrates the pH stability of development talks from within beyond that can be realised through focused oral delivery of a powerful drug without than expected were not statistically significant. stomelysin over acommittee range ofThe values soPhD academia. of Forum members, application basic research. development causing systemic side-effects. student Mreconomy Thomas Schwarzl as ensure noconclude significant The researchers thatirreversible current data of ato smart will depend on like-minded Under normal conditions, the gastrointestinal provides no evidence that individual residues collaborative partners opportunities denaturation of theidentifying enzyme during and realising basic and applied research experiments. They concluded that the synergies. This collaboration, initiated through stromelysin-1 catalytic domain (SCD) a SFI research supplement, highlights the is stablethat in the pH range 6.0-8.4companies for at potential innovative indigenous least 16with hours. From can theirrealise.” experiments working academia

“When we applied these new drugs to our IBD Reference: model, the gut was tricked into thinking that it Howe N, Ceruso M et al. pH stability of the was being deprived of oxygen. This activated stromelysin-1 catalytic domain and its mechanism of protective pathways, which in turn prevented interaction with a glyoxal inhibitor. BBA Proteins & the death of the cells that line the Proteomics (2011) 1394–1403 gastrointestinal tract,” explained Professor 13C NMR to determine if there Taylor. “Our pre-clinical trial data can now using Taylor’s collaboration with Sigmoid Pharma has inform the next phase Sigmoid Pharma product certainly been successful by these metrics with development pipeline”. three co-authored publications to date in two of HIV nef to arethe critical in determining the rate studies in humans shown that non Inofaddition product that is currently in the highest ranking have scientific journals in the of disease progression. Professor Denis is progression was associated with gross of the phase II clinical studies, Sigmoid Pharma field, Gastroenterology and Proceeding Shields believes that searches for modifiers deletions in the nef gene. developing a LEDDS™-enabled formulation ofof National Academy of Sciences, as well as the progression rates should now focus on other the hydroxylase inhibitor generation of proprietary innovative products However, much of the research in the area to Elaine Quinn host and viral factors. (DMOG) “Systematic evaluation dimethyloxaloylglycine to bring about and of high-skilled jobs. or case datethe hascreation been based on observational Communications &bioinformatics Education of large quantities of data by effective, safe and targeted delivery of thisOfficer studies rather than rigorous, systematic can beofjust as important refuting Research More than 15,000 people in Ireland and UCD Conway Institute Biomolecular &inBiomedical potential therapeutic agent. scientificofevaluation. This work doctoral hypotheses that are current in the literature, as millions people worldwide areby living with the University College Dublin candidate Ravindra Pushker out to it is in discovering unknown patterns”, he said. symptoms IBD today. Currentset therapeutic Belfield, Dublin 4 determine a substantially larger sample options for in this chronic debilitating diseaseset are if any association exists between disease This research was funded through Science Ireland very limited with surgery often being the only progression amino acid Foundation Ireland and University College viable option.and Theparticular Sigmoid product, currently E: elaine.quinn@ucd.ie differences deletions within the nef gene. Dublin. in a phase IIor clinical study, uniquely enables T: (+353-1) 716 6706 oral of a basis, powerful drug On adelivery per patient there waswithout no excess of F: (+353-1) 716 6701 causing systemic side-effects. LTNP patients with one or more defective nef W: www.ucd.ie/conway sequences when compared progressors. Under normal conditions, thetogastrointestinal Reference: While the high frequency of amino acid Meta-analysis to test the association of HIV-1 nef amino replacement at particular residues is indicative acid differences and deletions with disease progression.

Bioinformatic analysis of HIV progression studies

in the gastrointestinal tract, including the Meta-analysis by UCD researchers led by colon. Conway Fellow, Professor Denis Shields has determined there is no collaboration clear evidence The Sigmoidthat Pharma-Taylor is that particular defective viral in facilitating the development of sequences a new the HIV-1 nef gene orfor certain regions of the therapeutic approach the treatment protein play abowel significant role in disease inflammatory disease (IBD) by bringing progression. together the research methodology of the Taylor group with the proprietary HIV-infected patients can be categorised on liquid/emulsion drug delivery system, the basis of the number of years it takes for LEDDS®, developed by Sigmoid Pharma. them to progress AIDS. Some patients Investing in Your to Future maintain stable lymphocyte counts and Commenting onCD4 the award, Professor Taylor do not go are on to developfor AIDS even after said, “We delighted Dr Coulter andmore his than 10 of infection. team andyears indeed it reflects well on our partnership. A key driver of successful Scientists are curious as to why these longscientific research in 2010 is meaningful term, non- progressor (LTNP) patients do not interaction of academia with industry that develop AIDS. This may reflect differences in the host, viral genetics or environmental

May Issue 101 september 2007 Issue Issue 15,2010 Autumn 2011

Conway collaborator scoops Irish Times Innovation Award Improving Psoriasis with GLP-1 Analogue Therapy

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

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

GlycoExtractor advances glycan data manipulation cells, tissues and fluids. EUROCarbDB, a research infrastructure design Glycomics needs the supporting framework of extensive, well-curated databases and study funded by the EU 6th Framework Commercial packages that support HPLC flexible analytical tools. Currently, this field Programme. Prospective users can access the instruments cannot facilitate the extraction of GlycoExtractor tool on of study lacks the established, large quantities of data. In an effort to alleviate comprehensive and centralised data http://glycobase.nibrt.ie:8080/DemoGlycoExtra this bottleneck within high-throughput collections, standards and information ctor/mainPage. glycomic projects, the NIBRT team have reporting protocols that the existwealth within of Referencetract Imagine information Explaining how the team produced For Emma equates to is linedTeeling’s with cellsresearch, that blockthis the contents results in both academic outputs and thereliable Irish biopharmaceutical development developed a web-based tool that interfaces Research by Conway Fellow, Dr Oliver the function of worm Arl13b causes the complex traits including diabetes, GlycoExtractor: web-based interface forobesity, high genomics and that proteomics. of theAgut from leaking into the intestine. In an application of research toward clinicalmammal product company, Sigmoid recently scooped would be atPharma our fingertips ifwith wethe Waters timechromatography estimates of when different changes at genomic level underpinning software throughput processing of HPLC-Glycan data Blacque has revealedofnew information ciliary membrane to bulge and become mental retardation andiseven cancer. patient, this barrier broken and the companies.” theNatalia overall Innovation Year awardpackage at to development improvesplit, andwith automate the export Researchers, Dr Artemenko and Dr could understand thethe genetic groups sheindigenous said, “We used a ‘relaxed morphological and molecular Natalia V. IBD Artemenko, Matthew P. Campbell, and changes Pauline about a gene implicated in Joubert of data to various misshapen as well for as affecting the ability M. of Rudd Journal contents of the gutResearch, leak out2010, into surrounding the inaugural Irish Times All-Island of Proteome 9 (4), pp Matthew Campbell from the National Institute file formats subsequent basis and evolutionary history that clock’ approach that enables rates of DNA associated with flight and echolocation in Dr Oliver Blacque hopes that these findings Commenting on the Taylor collaboration, Dr 2037–2041 syndrome and related other proteins to properly distribute areas. The research team in UCD Conway used Innovation Awards. The cerebellar life-science SME, analysis. The architecture of the tool thewithin of Bioprocessing Research & Training (NIBRT) indisorders Coulter said,across “The collaboration with Taylor underlies the vast diversity form tomodular change the tree of mammals. We abats. “I personally will thisa phylogeny will ultimately lead by to applying a use greater model of IBD and, new class ofto founded bycharacterised UCD pharmacology graduate, Drfacilitates byRudd blindness, bone the ciliary membrane. led by Conway(JSRDs), Fellow, Professor Pauline also the manipulation of data from laboratory clearly demonstrates potential understanding onlythe of JSRDs, butwere also and function within used a large collection of welltheestablished explore in more detail evolution and drugs known as not hydroxylase inhibitors, Ivan Coulter, hasseen actively collaborated other with data management have developedabnormalities, an open access, web-based systems. cystic kidneys, that can befound realised through focused They also that a fully functional of closely related to almost completely the as and Conway Fellow, Professor Cormac Taylor mammals. fossil mammals to estimate rates of change able genetic control ofciliopathies visionreverse and such hearing interface that facilitates extraction, querying developmental delay and loss of muscle application of basic research. The development The NIBRT Arl13b team are nowbranches working to for integrate symptoms of theand disease. since being granted a Sciencein Foundation protein ispatient needed the normal Meckel syndrome, and sharing of tone HPLC-glycan data generated on the tree. This models to how thisGruber relates to Bardet-Biedl human disease”, she said. disease (CKD) and improve treatment, identify processes involved in early Conway researchers ledcontrol. by Dr. Tara and The findings of this of adifferent smart economy will of depend on like-minded GlycoExtractor with the EUROCarbDB Ireland industry research partnership award high throughput processes. functioning of a protein transport system in as well as perhaps more common CKD progression and investigate novel McMorrow and Professor Michael Ryan have with particular focus on CKD arising from An international collaboration including allowed us to convert the phylogentic tree “When we applied these new drugs to our IBD collaborative partners identifying opportunities research, framework to provide a comprehensive highin 2004. funded through a Science diabetes forispreventing and slowing the and hypertension. The multicilia. This transport system phenotypes cilium successfully secured €485,500 funding as model, the gutassociated was tricked into thinking that and realising basic and applied research She excited about thewith possibilities thatit the Conway Fellow, DrinEmma Teeling hasthroughput of evolutionary relationships into a strategies HPLC dataintraflagellar analysis platform for Glycosylation is the most common and Foundation Ireland President of Ireland The Irish Times award recognises the stellar progression of thedeprived disease. studies will and disciplinary research consortium hasbranches 25initiated part of an overall award to the Systems (IFT) makes contact with the ciliaryare dysfunction such as mental retardation was being ofThese oxygen. This activated This collaboration, through structurally diverse post-translational the storagesynergies. and annotation of experimental framework offers biologists for comparative created a phylogenetic framework using time-tree, in which the scaled Young Researcher Award (PIYRA) to Oliver innovative performance of Sigmoid Pharma in be integrated with clinical and epidemiological partners (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney protective pathways, which in turn prevented amembrane. research supplement, highlights on these results, the they obesity. in modification ofBlacque, proteins. More than half of all understand data. The integration of Based next generation research biomedicine, physiology large genetic datasets topublished better inSFI proportion toproject time. were recently in from the 15 their application of research and development. studies across theofconsortium systems and countries is due to run Disease Diagnosis and (SysKid) the death the cells thatusing line the potential that innovative companies gene products haveevolutionary beenTreatment shown history to be bioinformatic toolsand will further the indigenous proposed a the new working model for Arl13b, immunology. “Although Tree of Life is the of mammalian The company has developed two new drug biology methodologies inArl13b order to the develop new Journal of Cell Biology. He notes “That associates with ciliary for five years. gastrointestinal tract,” explained Professor working with academia can realise.” consortium under the European Union FP7 glycosylated. With many specific glycans or development of unified approaches for where it functions at the ciliary membrane technologies, andthe SmPill™, which not strategies and is treatment options to currently work inrequired progress, itcan provides a families and LEDDS™ theasrole of environment Using the time-tree, we initiatives were able to diagnostic Taylor. “Oura pre-clinical trial data now programme. membranes and for cilium glycoforms showing potential cancer handling large scale glycomics data One of seveninthe genes associated with JSRDs, to regulate important ciliary membrane Taylor’s collaboration with Sigmoid Pharma prevent has The of UCD Conway team, including postdoctoral only events enhance solubility and permeability CKD development. Email inform the next phase Sigmoid Pharma product benchmark that we can use into the future and earth history examine when different groups of with applications in been biomarker discovery biomarkers, there is an increasing need to in promoting structure/function in both worms and certainly successful by these metrics with researchers Dr. Craig Slattery and Dr. Natalia Syskid (www.SysKid.eu) was established to the drug but can deliver it to targeted locations Arl13b codes for a protein already known to properties such as shape, transmembrane tara.mcmorrow@ucd.ie detailsand of a PhD development pipeline”. NIBRT researchers Dr Matthew Natalia to decipher howforCampbell our genome functions and living biodiversity. mammals originated and diversified, and develop high throughput, highly sensitive and mammals demonstrates the Dr remarkable co-authored publications of in theroles gastrointestinal tract, including theMartin, will three utilise cell culture and animal position currently available. further our understanding chronic kidney This research was partially supported by to date in two play inof the and/or function protein distributions and IFT. Artemenko who developed GlycoExtractor robust strategies that detail the formation glycome of has evolved”. then associate factors that might have been evolutionary conservation of how this small In addition to the product that is currently in the highest ranking scientific journals in the colon. of cilia, which are hair-like projections phase II clinical studies, Sigmoid Pharma is field, and Proceeding of the Recently published in the journal Science, responsible theseago, diversification events. Up toGastroenterology only 20foryears many believed G-protein functions.” extending from the surfacecollaboration of the cell. is The Sigmoid Pharma-Taylor Reference: a LEDDS™-enabled formulation of developing National Academy of Sciences, well aspulse the the findings ofdevelopment the Tree ofofLife consortium For example, weredundant observed a as distinct most cilia to be cellular facilitating the the precise a new However, molecular details of Reference the hydroxylase inhibitor of proprietary innovative products organelles that have fallen victim are the culmination ofdoing a five led generation of diversification near the end ofto the Meredith et al. Impacts offunctions the Cretaceous therapeutic approach for the treatment of Joubert syndrome Arl13b at what exactly Arl13b is inyear ciliaproject have dimethyloxaloylglycine tociliary bring and the creation of high-skilled jobs. Terrestrial Revolution and(DMOG) KPg Extinction onin about mammalian evolution a type of cellular by scientists at the University of California, Cretaceous Terrestrial Revolution (80-82 membranes andand stabilizes protein transport inflammatory bowel disease (IBD) by bringing effective, safe targeted delivery of this remained unclear. Mammal Diversification. www.sciencexpress. More than 15,000 people in Ireland and Caenorhabditis elegans. Cevik S, Hori Y, Kaplan OI, appendix. We now know that these cellular together the research methodology of the Riverside (Prof. Mark Springer) and Texas million years ago) when flowering plants potential agent. 1/ doi:10.1126/ org/22 and fluids. EUROCarbDB, a therapeutic research infrastructure design Glycomics needs thegroup supporting framework Kida K, September Toivenon T, 2011/Page Foley-Fisher C, Cottell D, Katada T, millions ofpresent people worldwide are living the Taylor withstudied the proprietary Blacque’s team theMurphy). gene in thecells, cilia tissues antennae onand nearly all of ourwith cells A&M, USA (Prof. William started to diversify when most of the science.1211028 Commenting research, DrBiol. Kennedy to die as aIBD result of the raised New researchwell-curated led by Conway Fellow Dr study funded by EU 6th of extensive, databases andsystem, most likely symptoms Kontanion K, the Blacque OE. JFramework Cell 2010 Mar 22; today. Current therapeutic liquid/emulsion drug delivery of tiny worms (Caenorhabditis and serveinfundamental roles in many from Commercial packages that support HPLC mammalian orders began diverging glucose levels seen diabetes. Breandán Kennedy indicates that by treatment said, “By188(6):953-69 establishing a robust for early Programme. Prospective users model can access the flexible analytical tools. Currently, this fieldelegans) options for this chronic debilitating disease are LEDDS®, developed Sigmoid Pharma. instruments cannot facilitate the extraction of Tree of Life: http://mammaltree.informatics.sunysb. while collaborators the University of motility andwith sensory functions, including of diabetic blindness should look in atthe The study generated largest DNA one limited another”. study lacks the established, GlycoExtractor tool on retinopathy, we would and late stage diabetic very surgery often being the only Dr Kennedy and his team found that new blood large quantities of data. In an effort to alleviate edu/investigators.htm Commenting on theparallel award, Professor Taylor conducted in signalling pathways critical to development. protecting the Tokyo neurons responsible for experiments colour http://glycobase.nibrt.ie:8080/DemoGlycoExtra comprehensive and centralised data hope to better understand the progression of option. The sequence alignment from more than 99% vessels andviable thewithin neuronal cellSigmoid death inproduct, diabeticcurrently this bottleneck high-throughput said, “We arejust for07/05/2010 Dr his vision in thestandards eye and not targeting theCoulter ctor/mainPage. collections, and information cultured human cells. Together, theyand May 2010.qxd:Layout 1delighted copy 13:12 in Page 3II clinical disease and pave the way for identifying a phase study, uniquely enables the of mammalian families to build This phylogeny also serves as a framework retinopathy can arise independently of each glycomic projects, the NIBRT team have It is delivery now notofsurprising that defects in Reference team indeed it reflects well onuses our lipid blood vessels as is and currently the practice. reporting protocols that exist within athe powerful drug without drug targets for its successful treatment”. confirmed thattrees Arl13b other. In addition, they identified that cone developed aoral tool that interfaces evolutionary thatproteins depict how different toweb-based understand history of are theassociated uniquenew cilium structure and function partnership. A key driver of successful GlycoExtractor: A web-based interface for high genomics and anchors proteomics. causing systemic side-effects. to associate with the ciliary photoreceptor neurons, those involved in Nearly 2.5researchers million people worldwide are related blind models to processing identify involved in early disease and improve patient treatment, Conway led by Dr. in Tara with the (CKD) Waters chromatography software groups ofresearch mammals are to each changes in the genome underlying the vast of HPLC-Glycan data throughput The research was processes funded through Science scientific 2010 is meaningful with an ever expanding range of human membrane. colour vision and used daylight, are most due to diabetic retinopathy. This secondary CKD and investigate Researchers, Dr Natalia Drindustry package to Under improve and automate the export Nataliaprogression V. Artemenko, Matthew P. Campbell, and Pauline McMorrow and Professor Michael Ryan havefrom with particular focus oninCKD arising from normal conditions, the gastrointestinal Foundation Ireland and the Healthnovel Research interaction of academia with that other andArtemenko when theyand diverged each morphological diversity observed in called more diseases and syndromes, collectively M. Rudd Journal of Proteome Research, 2010, 9 (4), pp affected the high levels. complication of diabetes activates growthas strategies for preventing and slowing the Matthew Campbell from the National Institute of data toby various fileglucose formats for subsequent diabetes and hypertension. The multisuccessfully secured €485,500 inthe funding Board. other. than 5400 architecture living of 2037–2041 Much of thetowork on project was carried ciliopathies, whichspecies have of new blood vessels inthe theSystems eyethe and is progression of the disease. These studies will Bioprocessing Research & Training (NIBRT) analysis. The modular ofoverlapping themammals. tool clinical disciplinary research consortium has 25 part of leaky an overall award The research team made their observations Co-lead author on the publication, by UCD candidate, such as polycystic kidneys responsible forout the death ofdoctoral photoreceptors, led by Conway Fellow, Professor Pauline Rudd Sebihapartners also facilitates the manipulation of data from and be integrated with clinical and epidemiological (16features universities, 9 industry partners) Biology towards Novel Chronic Kidney using a novel zebrafish model of diabetes, the neurons that send visual messages to our Dr Emma Teeling’s research group, a Professor Mark Springer from have developed an open access, web-based other data management systems. studies across the consortium using systems Reference: Cevik. She and her colleagues went on to livers, retinal degeneration, bone from 15 countriesthe andearly the project is diabetic due tothe runUniversity Disease Diagnosis and Treatment (SysKid) which resembles stages of brain. interface thatunder facilitates extraction, querying methodologies in order to develop Predominant coneatphotoreceptor dysfunction in a new demonstrate in C. elegans how disrupting abnormalities, hydrocephalus, as wellyou as biology Science Foundation Ireland funded team of said, “When Arl13b ciliary membrane for five years. consortium the European Union FP7 retinopathy in California, humans. It Riverside is an exciting The NIBRT team are now working to integrate and sharing of and HPLC-glycan datathe generated in consortium, understand how taxa are related to each diagnostic strategies treatment diabetic options to hyperglycaemic model of and non-proliferative programme. members Treetoof Life development for the group who now hope to Until now, it was unclear if theofchanges GlycoExtractor with the EUROCarbDB retinopathy. Yolanda Alvarez, Jenneth Chen, Alison The UCD Conway team, including postdoctoral high throughput processes. prevent CKD development. Email further their and a vessels and neurons occurred independently produced the of bat data inresearchers the extend other…you pinpoint molecular framework to a can comprehensive highReynolds, Nore Waghorne, John O’Connor, Dr.provide Craigresearch Slattery andestablish Dr. key Natalia Syskid (www.SysKid.eu) wasmajority established to of tara.mcmorrow@ucd.ie for J. details of aBreandan PhD model of late stagedata diabetic one other and is which type common of retinal and neuron is Glycosylation the most throughput HPLC analysis platform for Kennedy. Disease Models & Mechanisms (2010) project. that aredisease. associated Martin, will changes utilise cell culture and animalwith key position currently available. further our understanding of chronic kidney Plecotus Auritus: the brown long-eared batthe found Meta-analysis by UCD researchers led by of HIV nef are critical in determining rateall studies in humans have shown that non structurally diverse post-translational the storage morphological and annotation changes”. of experimental over Ireland Fellow, Denis has The integration of disease progression. Professor Denis progression modification ofConway proteins. More Professor than half of all Shields data. of was nextassociated generationwith gross that there is no clear evidence Shields believes that searches for modifiers of deletions in the nef gene. bioinformatic tools will further the gene products determined have been shown to be particular defective viral sequences in progression rates should focus onMSc otherin glycosylated. With specific glycans oryou ofintroduced unified approaches for larger programmes suchnow as the new We 4ofnew advanced core Ithat ammany delighted to welcome to thedevelopment However, much the research in the area to the HIV-1 nef gene or certain regions ofhandling the host and viral factors. “Systematic evaluation glycoforms showing potential as cancer large scale glycomics data initiatives date has been based on observational or case technology modules on a pilot basis this Conway Focus and look forward to working Imaging commencing in September 2010. protein a significant of large quantities of data by bioinformatics biomarkers, there is anplay increasing need role to in disease with applications in biomarker discovery studies rather rigorous, systematic academic year;than those covering principlesNIBRT researchers progression. can be Dr just as important refuting with you inhighly the coming months! Matthew Campbellinand Dr Natalia develop high throughput, sensitive and scientific evaluation. This work by doctoral This was partially supported by award, Glycomics needs the supporting framework cells,research tissues and fluids. EUROCarbDB, a research infrastructure design who is developed GlycoExtractor are current inlandscape thethe literature, and practical ofMedal imaging and tract lined with cells that block contentsas results in both aspects academic outputs and theapplied Irish biopharmaceutical development Welcome! UCD Conway Festival Dr Artemenko shape the research funding robust strategies that detail the glycome of Ihypotheses hope that athat number of new initiatives, HIV-infected patients can be categorised on candidate Ravindra Pushker set out to study funded by the EUleaking 6thunknown Framework of extensive, well-curated databases andrecently scooped it the is in discovering patterns”, heInsaid. of gut from into the intestine. an application of research toward clinical product company, Sigmoid Pharma proteomics began late March and willset run Mark Pickering willinnow represent UCD in into the future. I look forward to working Commercial packages that support HPLC As an institute with an increasingly including the early-stage researcher forum the basis of the number of years it takes for determine in a substantially larger sample flexible analytical tools. Innovation Currently, of this Programme. Prospective usersiscan access IBD patient, this barrier broken and the the development with indigenous companies.” the overall thefield Year awardinstruments at cannot facilitate the extraction of until mid-June with a further two modules in This issue follows the tremendous the Roche ‘National Researcher of the Year’ within our research community in this new them to progress to AIDS. Some patients if any association exists between disease This research was funded through Science research focus and GlycoExtractor tool on of study lacks interdisciplinary the inaugural established, described this willinto notsurrounding only contents of in the gutissue, leak out the Irish Times All-Island large of data. In an effort to alleviate maintain stable CD4 lymphocyte counts and quantities progression and particular amino acid Foundationyear Ireland and University College genomics and cytometry Commenting on the Taylor collaboration, Dr http://glycobase.nibrt.ie:8080/DemoGlycoExtra success of the 11thdata annual UCD Conway competition inflow November. Wetaking wishplace him academic to harness our collective comprehensive and centralised areas. The research team in UCD Conway used Innovation Awards. The life-science SME, expertise in specialist technology platforms, strengthen the community of Conway this bottleneck within high-throughput do not goof onResearch to develop even after more differences deletions within the nefthe gene. Dublin. and strive to achieve our Coulter said,or“The collaboration with Taylor ctor/mainPage. collections, standards and information over week-long during the summer Festival & AIDS Innovation, which every success inperiods the event! astrengths model of IBD and, by applying a new class of founded by UCD pharmacology graduate, Dr glycomic projects, the NIBRT team have we are uniquely placed to participate in the researchers and forge new interdisciplinary than 10 years of within infection. laboratory clearly demonstrates the potentialReferencedrugs reporting protocols that exist months. known as hydroxylase inhibitors, were Ivan Coulter, hasoutstanding actively collaborated with celebrated the achievements strategic goals. On a per patient there was no excess of developed athat web-based toolbasis, that interfaces can be realised through focused and training ofto the next Taylor linkstoAbut will celebrate heighten GlycoExtractor: web-based interface and for high genomics and education proteomics. able almost completely reverse the Conway Fellow, Professor Cormac Scientists are curious why these longLTNP patients with one or more defective nef of our researchers inasthe past year. The As we enter the second decade since with the Waters chromatography software throughput processing ofresearch, HPLC-Glycan application of basic research. The development Commenting on the Drdata Kennedy most likely to die as a result of the raised New research generation led by Conway Fellow Dr of research scientists. The newly symptoms of the disease. since being granted a Science Foundation awareness of our research and innovation term, nonprogressor (LTNP) patients do not sequences when compared to progressors. Researchers, Dr Natalia Artemenko and Dr highlighted package to of improve and automate the Institute, export We hope to determine from this pilot if Artemenko, Matthew P.Kolch Campbell, and Pauline Natalia V. Professor moderated poster sessions the establishment of the we Walter a smart economy will depend on like-minded glucose levels seen inhigh diabetes. Breandán Kennedy indicates that treatment said, “By establishing a robust model early Reference: Ireland industry research partnership award develop AIDS. This may reflect differences While the frequency of amino acid M. Rudd Journal of Proteome Research, 2010, for 9 (4), launched PhD programme in are Bioinformatics Matthew Campbell from the National Institute data to various filefor formats for subsequent successes. we applied these new drugs to pp ouramino IBD collaborative partners identifying demand training from withinopportunities UCD as well how basic research findings beingof in are consolidating our research expertise Director Meta-analysis to test the association of would HIV-1 nef of diabetic blindness look at and late“When stage diabetic retinopathy, we in 2037–2041 the2004. host,should viral&genetics or(NIBRT) environmentalanalysis. replacement at found particular residues is indicative of Bioprocessing Research Training The modular architecture of theresearch tool Dr Kennedy and his team that new blood acid differences and deletions with disease progression. model, the gut was tricked into thinking that it and realising basic and applied and Systems Biology recently attracted 80 as from evolvement, external academic centres and into clinical industrial in order to dynamically respond to the protecting the translated neurons responsible forand colour hope to better understand the progression of factors that could potentially be exploited for of rapid permutation testing IrishProfessor Times award recognises led by Conway The Fellow, Pauline Rudd the stellar also facilitates manipulation of data from through Ravindra Pushker, Jean-Marc Jacquē,This Denisactivated C. Shields. vessels andsynergies. thethe neuronal cell death in diabetic was being deprived of oxygen. This collaboration, initiated vision in the eye and not just targeting the forimpact Professor Walter Kolch EU and 120 non-EU applicants up other to 15 industry will dictate stand-alone delivery that will positively our prevailing funding environment and to of the disease and theApr way for identifying the of the disease. showed that residues with more Journal of pave Virology, 2010 p3644-3653 innovative performance of Sigmoid Pharma in data management have developedapplications antreatment open access, web-based systems. retinopathy independently eachreplacements protective pathways, which in turn prevented acan SFI arise research supplement,ofhighlights the blood vessels studentships. as is currently the practice. new drug targets for its successful treatment”. than expected were not statistically significant. these advanced modules or inclusion within Director, UCD society into theoffuture. Arising from his proactively engage with stakeholders to their application research and development. interface that facilitates querying other. In addition, they identified that cone the death of the Conway cells thatInstitute line the potential Studies inextraction, model organisms have shownThe thatNIBRT team arethat nowinnovative working indigenous to integratecompanies company has two new drug and sharing of The HPLC-glycan datadeveloped generated photoreceptor those involved incurrent data The research Nearly 2.5 million people worldwide are blind gastrointestinal tract,” explained Professor working with academia canthat realise.” was funded through Science infection with nef-deficient virusinshows an Theneurons, researchers conclude GlycoExtractor with the EUROCarbDB LEDDS™ and SmPill™, which not vision and used in daylight, are most high throughput processes. colour due to diabetictechnologies, retinopathy. This secondary Taylor. “Our and pre-clinical trial Research data can now provides that individual residues attenuated course of infection and someframework to Foundation Ireland the Health providenoa evidence comprehensive high-Pharma with Sigmoid has enhance the solubility and permeability of by Taylor’s affected the highcollaboration glucose levels. complication ofonly diabetes activates the growth Board. inform the next phase Sigmoid Pharma product Glycosylation isthe the most and to targeted locations throughput certainly HPLC data analysis platform for metrics with been successful by these butcommon can deliver of new leaky blooddrug vessels in the eye itand is development pipeline”. structurally diverse post-translational the storage and annotation ofpublications experimental The research team made their observations three co-authored to date in two of in the gastrointestinal tract, including the responsible for the death of photoreceptors, modification of proteins. More than half of all data. integration of model next generation usingThe a novel zebrafish of diabetes,

Conway collaborator scoops Irish Times Worm research reveals cilia disease geneInnovation functionAward Creating the Tree of Life

Success in EU FP7 call

GlycoExtractor glycaninto datadiabetic manipulation Zebrafish modeladvances gives insights blindness Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Director’s Message

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

Zebrafish model gives insights into diabetic blindness

UCD CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH


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Conway collaborator Irish Times Innovation Award Comparing Effectiveness in scoops Rheumatoid Arthritis Therapeutics

Conway collaborator scoops Irish Times Innovation Award Conway collaborator TimesFestival Innovation Award Neurotherapeutic Researchscoops ScoopsIrish Conway Medal Irish biopharmaceutical development company, Sigmoid Pharma recently scooped Dr Pickering was awarded the IrishMark biopharmaceutical development the overall Innovation of therecently Year at company, Pharma scooped 2011 UCDSigmoid Conway Festival ofaward Research the inaugural Irish Times All-Island theInnovation overall Innovation of the Year award at & gold medal, sponsored Innovation Awards. The life-science SME, the Roche, inaugural All-Island by forIrish hisTimes research to identify founded UCDofpharmacology graduate, Awards. The life-science SME,Dr aInnovation novel by class remyelinating agent Ivan Coulter, haspharmacology actively collaborated founded by UCD graduate, Dr with potential therapeutic use in with Conway Fellow, Cormac Taylor Ivan Coulter, hasProfessor actively collaborated with myelination disorders such as multiple Conway Fellow, Professor Cormac Taylor since being granted a Science Foundation sclerosis. He will now represent UCD since being granted a Science Foundation Ireland industry research partnership award in the Roche ‘National Researcher Ireland in 2004.industry research partnership award of the Year’ competition, which in 2004. The Irish Times recognises takes place onaward November 8ththe instellar the The Irish Times award recognises the stellarin innovative performance of Sigmoid Pharma Radisson Blu Hotel, Golden Lane, innovative performance of Sigmoid Pharma in their application of research and development. Dublin. theircompany application research and The hasofdeveloped twodevelopment. new drug The company LEDDS™ has developed two new which drug not technologies, and SmPill™, A postdoctoral researcher in the which not technologies, LEDDS™ and and SmPill™, only enhance the solubility permeability of Neurotherapeutics Research Group led of only enhance the solubility and permeability the drug but can deliver itKeith to targeted locations by Conway Fellow, Dr Murphy, the drug but can deliver it to targeted locations in the gastrointestinal tract, including the Dr Pickering hisincluding competitors May 2010.qxd:Layout 1staved copyoff 07/05/2010 in the gastrointestinal tract, the 13:12 colon. and impressed the judging panel with a colon. concise overview of this research project The Sigmoid Pharma-Taylor collaboration is The Sigmoid Pharma-Taylor collaboration is and its innovative potential. facilitating of aa new new facilitating the the development development of therapeutic approach for the the treatment treatment of therapeutic approach for of He explained that although therapeutic inflammatory bowel disease (IBD) by bysuch bringing inflammatory bowelon disease (IBD) bringing agents currently the market, together the methodology of the the together the research research methodology of as interferon beta and natalizumab, Taylor group with the proprietary produce significant benefits in liquid/emulsion drug delivery system, LEDDS®, developed by Sigmoid Pharma. Commenting on the award, Professor Taylor said, “We are delighted for Dr Coulter and his team and indeed it reflects well on our partnership. A A key key driver driver of partnership. of successful successful scientific research research in in 2010 scientific 2010 is is meaningful meaningful interaction of of academia academia with interaction with industry industry that that

results in both academic outputs and the application of research toward clinical product multiple sclerosis, they are limited in results in both academic outputs and the development indigenous targeting inflammation andcompanies.” immuneapplication of with research toward clinical product mediated damage, and are companies.” ineffectiveDr development indigenous Commenting with on the Taylor collaboration,

in progressive disease types. The Coulter said, “The with the Taylor Commenting on thecollaboration Taylor collaboration, Dr Neurotherapeutics Research Group has laboratory clearly demonstrates potential Coulter said, “The collaboration with the that Taylor instead focused on finding anthe agent that induce can beclearly realised through focused laboratory demonstrates the potential can remyelination.

application basic through research.focused The development that can be of realised application of basic research. The development of a smart economy will depend on like-minded Using an in-vitro system, the team of a smart for economy will depend on like-minded collaborative partners identifying opportunities screened potential remyelinating collaborative partners opportunities and realising basic andidentifying applied agents before progressing toresearch validate and realising basic and applied research synergies. This collaboration, initiated through results in-vivo. Outlining their findings, synergies. collaboration, initiated through a SFI research supplement, highlights the Mark said,This “We saw that UCD-MS1 apotential SFI research supplement, highlights the accelerated repair after companies that myelin innovative indigenous potential that innovative indigenous cuprizone-induced, working with academianon-inflammatory can realise.”companies working with academia can realise.” demyelination in murine models. The Taylor’s collaboration with Sigmoid Pharma has promyelin properties UCD-MS1 mayhas Taylor’s collaboration withof Sigmoid Pharma certainly been successful by these metrics with not be unique to this compound as we certainly been successful by these metrics with three co-authored publications to date in two of have identified three structurally Page 3 three co-authored publications to daterelated in two of the highest ranking scientific journals in the compounds that display similar efficacy the highest ranking scientific journals in the in vitro.” field, Gastroenterology and and Proceeding Proceeding of of the the field, Gastroenterology National Academy Academy of of Sciences, Sciences, as as well well as as the the National He believes UCD-MS1 may be generation ofthat proprietary innovative products generation of proprietary innovative products useful a single in myelination and the theas creation of therapy high-skilled jobs. and creation of high-skilled jobs.

disorders, or synergistically with an More than than 15,000 15,000 people people in Ireland Ireland and immunomodulatory agent. Additionally, More in and millions of of people people worldwide are living living with the the UCD-MS1 mightworldwide be deployed in nonmillions are with symptoms IBD today. Current therapeutic therapeutic debilitating disease disease are are options for this chronic debilitating very limited with surgery often often being being the the only only viable option. The Sigmoid product, product, currently currently in a phase II clinical study, uniquely uniquely enables enables oral delivery of a 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 intoblock the intestine. In an inflammatory myelinopathies forcontents which tract lined withleaking cells that the IBD patient, thiscurrently barrierinto isexist. broken and theIn an nothe therapies of gut from leaking the intestine. contents of the leakisout into surrounding IBD patient, thisgut barrier broken and the areas. The research team inwere UCDsurrounding Conway used contents ofthirty the gut leak out into In total, abstracts shortlisted afor model ofresearch IBD and,to byjudging applying aConway new in class areas. The team in UCD usedof presentation panels hydroxylase inhibitors, wereof adrugs model of IBDasand, byposter applying a new class the sixknown moderated sessions held able almost reverse the overtothe course of the one-day event. drugs known ascompletely hydroxylase inhibitors, were Eachtoof the category winners able almost completely thewere symptoms of six the disease. reverse then givenofninety seconds in which to symptoms the disease. “When we applied theseofnew to our IBD persuade the judges thedrugs importance of “When we these drugs towinners ourthat IBDit model, theapplied gut was tricked into thinking their research. The sixnew category model, the deprived gut was tricked into thinking that it was of oxygen. This activated werebeing Drs Mark Pickering, Jens Rauch, was being deprived ofwhich oxygen. This activated protective pathways, in turn Fiona Furlong, Luis Alvarez, Alexprevented Cheong, protective pathways, in turn Emma the deathBörgeson. of the cellswhich that line the prevented the death of the tract,” cells that line theProfessor gastrointestinal explained gastrointestinal tract,” explained Taylor. “Our pre-clinical trial dataProfessor can now Taylor. “Our pre-clinical trial data can now inform the next phase Sigmoid Pharma product inform the next phase Sigmoid Pharma product development pipeline”. development pipeline”. In addition to the product that is currently in In addition to the product that is currently in phase clinical studies, studies, Sigmoid Sigmoid Pharma Pharma isis phase IIII clinical developing aa LEDDS™-enabled LEDDS™-enabled formulation formulation of of developing the hydroxylase hydroxylase inhibitor inhibitor the dimethyloxaloylglycine (DMOG) (DMOG) to to bring bring about about dimethyloxaloylglycine effective, safe safe and and targeted targeted delivery delivery of of this this effective, potential therapeutic therapeutic agent. agent. potential Dr Hugh Brady, UCD President (left) and Dr Mark Pickering, UCD Conway Festival gold medal winner.

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

LOX proteins are involved in cross-linking results in both academic outputs and the collagen in the toward extracellular matrix, applicationfibres of research clinical product thus enhancing scarring and development withfibrotic indigenous companies.” contributing to loss of renal function. Dr Commenting on the that Taylorthese collaboration, Higgins identified hypoxia-Dr Coulter said, “The collaboration with the Taylor inducible targets are up-regulated early laboratory clearly the studies in disease humansdemonstrates have pivotal shown that non in kidney and for potential disease studies have shown non that can in behumans realised through focused progression was associated withthat gross development.

tract lined withShe cells thatproposes block the to contents renalisdisease. now of the gut from into as theaintestine. In an evaluate LOXleaking inhibition therapeutic IBD patient,for this barrier is brokenofand the strategy early treatment renal disease of through number of contents the gut use leakof outa into surrounding complementary in vivo areas. The researchand teamappropriate in UCD Conway used amodels. model of IBD and, by applying a new class of of HIV nef are critical in determining the rate drugs ascritical hydroxylase inhibitors,the were of disease HIVknown nef progression. are in Professor determining rate of Denis able tocollaborators almost completely reverse the “My on this project will of disease progression. Professor Denis Shields believes that searches for modifiers symptoms of the disease. in the process of of provide vital expertise Shields believes that searches for modifiers progression ratesbasic should now focus on otherof translating my research findings progression rates should now focus on “When weclinical applied these new drugs to ourother IBD host and viral factors. “Systematic evaluation into the setting and industrial host and viral factors. “Systematic evaluation model, the gut was tricked into thinking that it of large quantities of data by bioinformatics application”. of large quantities of data bioinformatics was being deprived oxygen. This activated can be just as important inby refuting protective pathways, can beinclude just as important inin refuting hypotheses thatconsultant are which current inturn the prevented literature, as They nephrologists, the death of the cells that linein the it is in discovering unknown patterns”, he said. hypotheses that are current the literature, as Dr Denise Sadlier, Mater Misericordiae gastrointestinal tract,” explained Professor it is in discovering unknown he said. University Hospital andthrough Drpatterns”, John Holian, This research was funded Science Taylor. “Our pre-clinical trialHospital; data can now St. University Foundation Ireland and University College ThisVincent’s research was funded through Science inform the next phase Sigmoid Pharma product UCD academic sponsor and Conway Dublin. Foundation Ireland and University College development pipeline”. Fellow, Prof Catherine Godson, UCD Dublin. School of toMedicine & Medical Science; In addition the product that is currently in international partners, Profis phase II clinical academic studies, Sigmoid Pharma Barbara Murphy, Mount Sinai, New of developing a LEDDS™-enabled formulation Reference: York and Prof Amato Giaccia, Stanford the hydroxylase inhibitor Meta-analysis to test the association of HIV-1 nef amino University; industrial Drabout Reference: dimethyloxaloylglycine (DMOG) to bring acid differencesand and deletions with partner, disease progression. Cormac Kilty, CEO of Argutus Medical, a Meta-analysis toand test the association ofDenis HIV-1 nef amino Ravindra Pushker, Jean-Marc Jacquē, Shields. effective, safe targeted delivery ofC.this acid differences andApr deletions withdevelopment disease progression. Journal of Virology, 2010 p3644-3653 company involved in the of potential therapeutic agent.

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

the HIV-1 nefagene or certain of the protein play significant role regions in disease The Irish Times award recognises the stellar

protein play a significant role in disease progression. Chronic disease associated innovativekidney performance of isSigmoid Pharma in progression. with poor health outcomes and highon HIV-infected patients can be and categorised their application of research development. economic cost. There is a significant lack the basis of the number takes for HIV-infected patients canofbeyears categorised on The company has developed two itnew drug of reliable biomarkers to identify early them to progress to AIDS. Some patients technologies, LEDDS™ SmPill™, which the basis of the numberand of years it takes for not stage renal injury and toand predict those maintain stable lymphocyte counts only enhance theCD4 solubility permeability of them to progress toprogress AIDS. Some patientsand patients likely to to chronic and do not oncan to CD4 develop even after more the druggobut deliver itAIDS to targeted locations maintain stable lymphocyte counts and end-stage kidney disease. than 10 years of infection. in tract, including the more dothe notgastrointestinal go on to develop AIDS even after colon. than 10 years of infection. Scientists areofcurious as to why these longThe degree tubulointerstitial fibrosis

term,Sigmoid non-are progressor (LTNP) patients do is not correlates with progression ofthese the disease The Pharma-Taylor collaboration Scientists curious as to why longdevelop AIDS. This may reflect in and decline indevelopment renal function. Dr Higgins facilitating the of patients adifferences new term, nonprogressor (LTNP) do not has shown that hypoxia occurs early the host, viral genetics orthe environmental therapeutic approach for treatment of develop AIDS. This may reflect differences in in kidney and promotes disease factors thatinjury could potentially be exploited for inflammatory bowel disease (IBD) by bringing the host, viralthrough genetics up-regulation or environmentalof a progression the treatment of the disease. together the research methodology of the factors that potentially processes. be exploited for number of could pro-fibrogenic Taylor group with the proprietary Studies in model organisms the treatment of the disease. have shown that liquid/emulsion drug delivery system, infection with nef-deficient virus shows an LEDDS®, developed by Sigmoid Pharma. Studies in model attenuated courseorganisms of infectionhave andshown some that infection with nef-deficient showsTaylor an Commenting on the award, virus Professor attenuated course of infection and some said, “We are delighted for Dr Coulter and his team and indeed it reflects well on our partnership. A key driver of successful scientific research in 2010 is meaningful

progression was associated application basic research. The gross development deletions inofthe nef gene. with deletions in the nef gene. of a smart economy will depend on like-minded Debra Higgins proposes to devise However, much of theidentifying research inopportunities the novel area to collaborative partners diagnostic products for renal in disease However, much of theon research the area to date has been based observational or by case and realising basic and applied research analysing LOX expression in human date hasrather been than basedrigorous, on observational orblood, case studies systematic synergies. This collaboration, initiated through urine and biopsy from studies rather thansamples rigorous, systematic evaluation. This work by patients doctoral ascientific SFI acute research supplement, highlights the with and chronic kidney injury. candidate Ravindra Pushker set out to scientific evaluation. This work by potential that innovative indigenousdoctoral companies determine in academia a substantially larger set candidate Ravindra Pushker set outsample to working with can realise.” “By correlating expression levelssample of LOX ifdetermine any association exists between in a substantially largerdisease set and hypoxia regulated proteins with Taylor’s collaboration withbetween Sigmoid Pharma has progression and particular amino disease acid if any association exists degree of kidney damage in acute kidney certainly been successful byamino these metrics with differences orand deletions within the acid nef gene. progression particular injury or chronic kidney disease, I aim to of three co-authored publications to date in two differences or deletions within the nef gene. On highest a per LOX patient therebiomarker was no excess validate asbasis, anscientific early the ranking journals inof the of renal injury and develop an appropriate LTNP patients with oneand or more defective nefof On a Gastroenterology per patient basis, there was no excess field, Proceeding of the detection strategy for point ofdefective careasuse in sequences when compared to progressors. National Academy ofone Sciences, as well the LTNP patients with or more nef the clinic”, she said. While the high frequency of amino acid generation of proprietary innovative products sequences when compared to progressors. replacement at particular residues is indicative and thethe creation of high-skilled jobs. While high frequency of amino acid of rapid evolvement, permutation testing Dr Higgins has already shown that replacement at particular residues is indicative More than 15,000 people Ireland and showed that residues withinmore replacements inhibiting LOX activity the body of rapid evolvement, permutation testing millions of people worldwide are living can against development ofwith the thanprotect expected were not statistically significant. showed that residues with more replacements symptoms IBD today. Current therapeutic The researchers conclude that current data are than expected were not statistically significant. options for this chronic debilitating disease provides no with evidence thatoften individual residues very limited surgery being the only The researchers conclude that current data viable option. The Sigmoid product, currently provides no evidence that individual residues in a phase II clinical study, uniquely enables oral delivery of a powerful drug without causing systemic side-effects.

information the relative efficacy results in bothofacademic outputs and the between anti-TNFtoward α agents, it isproduct applicationthe of research clinical difficult for clinicians to make an informed development with indigenous companies.” choice of agent.

on the Taylor collaboration, Dr Success in EU FP7 call Commenting Coulter said, “The collaboration the Taylor Bayesian MTC model waswith chosen Success in EU FP7 call The laboratory clearly demonstrates the potential for the flexibility to include more data Ivan Coulter, has actively collaborated with

that can be realised through focused Researchers at St Vincent’s University and handle more complex modelling Conway Fellow, Professor Cormac Taylor disease (CKD) and improve patient treatment, Conway researchers ledCentre by Dr. Tara application of basic research. The development Hospital, the National of structures. The trials measured the since being granted a Science Foundation of a smart economy will depend on like-minded McMorrow and Professor Michael Ryan have with particular focus on CKD arising Pharmacoeconomics and the Department disease (CKD) and improve patient treatment, Conway researchers led by Dr. Tara response to treatment using eitherfrom the Ireland industry research partnership award collaborative partners opportunities diabetes and hypertension. multiof Statistics, Trinity Dublin ledhave by successfully secured €485,500 inRyan funding as American Rheumatology (ACR) McMorrow and Professor Michael with particular focusof onidentifying CKDThe arising from in 2004. May 2010.qxd:Layout 1 copyCollege 07/05/2010 13:12 Page 3College and realising basic and applied research Conway Professor Oliver Fitzgerald disciplinary research consortium has 25 part of anFellow, overall award to the Systems response criteria or the Health Assessment diabetes and hypertension. The multisuccessfully secured funding The Irish Times award€485,500 recognisesinthe stellaras synergies. This collaboration, initiated through analysed 16 published trials a Questionnaire (HAQ). ACR measures the partners (16 universities, 9 industry partners) Biology Novel Chronic Kidney disciplinary research consortium has 25 part of antowards overall awardof toSigmoid theusing Systems innovative performance Pharma in a SFI research supplement, highlights the of Bayesian mixed treatment comparison relative improvement in a defined set from 15 countries and the project is due to run Disease Diagnosis and Treatment (SysKid) partners (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney their application of research and development. potentialwhile that innovative indigenous companies (MTC) model. criteria HAQ at theisextent for five from 15 years. countries andlooks the project due toof run consortium under the Union FP7 Disease Diagnosis andEuropean Treatment (SysKid) The company has developed two new drug working withdisability academiaincan functional therealise.” disease. for five years. consortium under the European Unionwhich FP7 not programme. technologies, LEDDS™ and SmPill™, Each of the five tumour necrosis factorThe UCDcollaboration Conway team, Taylor’s withincluding Sigmoidpostdoctoral Pharma has programme. only enhance the solubility and permeability of α (TNF(www.SysKid.eu) α )antagonists;was adalimumab, The UCD Conway team, including postdoctoral The study found that the rank of with researchers Dr. Craig Slattery andorder Dr. Natalia Syskid established to certainly been successful by these metrics the drug but can deliver it to targeted locations certolizumab, etanercept, researchers Dr. Craig and Dr. Natalia Syskid (www.SysKid.eu) was golimumub established to efficacy when using the HAQ is two of Martin, will utilise cellSlattery culture and animal further our understanding chronic kidney three co-authored publications toscore date in in the gastrointestinal tract,ofincluding the and infliximab have shown considerable etanercept, certolizumab, Martin, will utilise cell cultureadalimumab, and animal further the highest ranking scientific journals in the colon. our understanding of chronic kidney efficacy compared to a placebo control in golimumub and infliximab. The mostof the field, Gastroenterology and Proceeding randomised controlled trials with patients effective agents throughout trials The Sigmoid Pharma-Taylor collaboration is National Academy of Sciences, the as well as were the who showthe an development inadequate of response etanercept certolizumab. Thisproducts may facilitating a new to generation ofand proprietary innovative conventional disease-modifying antibe due to the fact that they are less likely therapeutic approach for the treatment of and the creation of high-skilled jobs. rheumatic drugs such as methotrexate. to stimulate the body’s immune response inflammatory bowel disease (IBD) by bringing However, little methodology comparativeof the than therapies. More antibody than 15,000 people in Ireland and together thewith research

Commenting oncells the that significance the tract is lined with block theof contents study, Professor Oliver FitzGerald said,In an of the gut from leaking into the intestine. “This comparative effectiveness estimate IBD patient, this barrier is broken and the for anti-TNF αgut agents mayinto besurrounding a useful tool contents of the leak out when The cost-effectiveness a consideration areas. research team inisUCD Conway used the choice drugs. It coulda be used ainmodel of IBDof and, by applying new class of withinknown the clinical setting as part of awere drugs as hydroxylase inhibitors, matrix of decision-making tools” able to almost completely reverse the models to identify processes involved in early symptoms of the disease. CKD progression and investigate novel Reference models to identify processes involved in early Schmitz Swe et al. treatment “When applied these new drugs to of our strategies forA mixed preventing andcomparison slowing thetheIBD CKD progression and investigate novel efficacy of anti-TNF agents in rheumatoid arthritis forwill model, the gutof was tricked into thinking that it progression the disease. These studies strategies for preventing and slowing the methotrexate non-responders demonstrates differences was being deprived of oxygen. This activated be integrated with clinical and epidemiological progression of the disease. These studies will between treatments: a Bayesian approach. Ann Rheum Dis protective pathways, which in epidemiological turn prevented studies across theclinical consortium using systems be integrated with and (2011) doi:10.1136/annrheumdis-2011-200228 the death of thethe cells thatinline the biology methodologies order to develop studies across consortium using systemsnew gastrointestinal tract,”and explained diagnostic strategies treatment options to biology methodologies in order toProfessor develop new Taylor. pre-clinical data can now to diagnostic strategies andtrial treatment options prevent“Our CKD development. Email inform the phase Sigmoid Pharma prevent CKDnext development. tara.mcmorrow@ucd.ie forEmail details of a product PhD development pipeline”. for details of a PhD tara.mcmorrow@ucd.ie position currently available. position currently available.that is currently in In addition to the product phase II clinical studies, Sigmoid Pharma is developing a LEDDS™-enabled formulation of the hydroxylase inhibitor dimethyloxaloylglycine (DMOG) to bring about effective, and targeted Patient withsafe rheumatoid arthritisdelivery of this potential therapeutic agent. EUROCarbDB, a research infrastructure design EUROCarbDB, a research infrastructure design study funded by the EU 6th Framework study funded by the EU 6th Framework Programme. Prospective users can access the Programme. Prospective users can access the GlycoExtractortool toolon on GlycoExtractor http://glycobase.nibrt.ie:8080/DemoGlycoExtra tract is lined withbut cells contents nucleic acids) canthat runblock on athe personal http://glycobase.nibrt.ie:8080/DemoGlycoExtra ctor/mainPage. of the gut from leaking into the intestine. In an ctor/mainPage. computer or over a server and is available IBD patient, this barrier is broken and the atReference http://www.clustal.org. Science Reference Aweb-based web-based interface forhigh high GlycoExtractor: contents of the gut leak out into surrounding AIreland interface for GlycoExtractor: Foundation funded this research. processing ofHPLC-Glycan HPLC-Glycan data throughput throughput areas. Theprocessing researchofteam in UCDdata Conway used Natalia V. Artemenko, Matthew P. Campbell, andclass Pauline V. Artemenko, Matthew P. Campbell, and Pauline aNatalia model of IBD and, by applying a new of M. Rudd Journal of Proteome Research, 2010, 9 (4), Des Higgins theinhibitors, original M. Rudd Journal developed of Proteome Research, 2010, 9 Clustal (4), pppp drugs known as hydroxylase were 2037–2041 2037–2041 programme aligningreverse proteinthesequences able to almostfor completely in 1988, which become one of the symptoms of the has disease.

GlycoExtractor advances advances glycan glycan data data manipulation manipulation GlycoExtractor

Conway The collaborator Irish Times Innovation Award Clustal Omega: Ultimatescoops Alignment Programme?

cells, tissues and fluids. Glycomics needs the proprietary supporting framework millions of people worldwide are living with the Taylor group withthe the cells, tissues and fluids. Glycomics needs supporting framework of extensive, well-curated databases and symptoms IBD today. Current therapeutic liquid/emulsion drug delivery system, and of extensive, well-curated databases Commercial packages that support HPLC flexible analytical tools. Currently, this field Commercial packages support HPLC options for this chronicthat debilitating disease are LEDDS®, developed by Sigmoid Pharma. flexible analytical tools. Currently, this field instruments cannotfacilitate facilitate the extraction instruments the extraction ofof very limited cannot with surgery often being the only of study lacks the established, of study lacks the established, large quantities of data. In an effort toalleviate alleviate Commenting on and the award, Professor Taylor large quantities of data. In an effort to viable option. The Sigmoid product, currently comprehensive centralised data results in both academic outputs and the Irish biopharmaceutical development How would you the sequence generate unacceptably poor quality comprehensive andcompare centralised data this bottleneck within high-throughput said, “We arestandards delighted for Dr Coulter and his this within high-throughput in a bottleneck phase IIofclinical study, uniquely enables collections, and information application research toward clinical product company, Sigmoid Pharma recently scooped of a histone protein across 10,000 collections, standards and information alignments or they are accurate yet team and indeed it reflects well on our glycomic projects, the NIBRT team have glycomic projects, the NIBRT team have oral delivery of a powerful drug without reporting protocols that exist within development with indigenous companies.” the overall Innovation ofexist thenow Year award at reporting protocols that within different species? Until the prohibitively intensive of computing partnership. A key driver of successful developed web-based toolthat thatinterfaces interfaces developed aaweb-based tool causing systemic side-effects. genomics and proteomics. the inaugural Irish Times genomics and question wasproteomics. partly anAll-Island one power. scientific research in 2010 isabstract meaningful withthe theWaters Waters chromatography software Commenting onchromatography the Taylor collaboration, Dr with software Innovation Awards. The life-science SME, Under normal conditions, the gastrointestinal because technology for generating interactionthe ofDr academia with industry that Coulter said, “The collaboration with the Taylor package improve andautomate automate the export Researchers, Dr Natalia Artemenko and Dr Dr Researchers, Natalia Artemenko and Dr package totoimprove and the export founded by UCD pharmacology graduate, sequences was slow and expensive. UCD led by Professor Des laboratory clearly file demonstrates the potential ofdata dataresearchers various file formats for subsequent Matthew Campbell fromthe thecollaborated National Institute Matthew Campbell from National Institute of totovarious formats for subsequent Ivan Coulter, has actively with that can be realised through focused Higgins and their collaborators inthe of Bioprocessing Research & Training (NIBRT) analysis. The modular architecture thetool tool of Bioprocessing Research & Training (NIBRT) analysis. The modular architecture ofof Conway Fellow, Professor Cormac Taylor application of basic research. The Today, rapidgranted advances in technology Europe, Asia and the USA have addressed led by Fellow, Pauline also the ofofdevelopment data led byConway Conway Fellow,aProfessor Professor PaulineRudd Rudd alsofacilitates facilitates themanipulation manipulation datafrom from since being Science Foundation of a smart economy depend on like-minded May 2010.qxd:Layout 1 an copy 07/05/2010 13:12 other Page 3management have developed open web-based data systems. and the falling cost ofaccess, genome have developed an open access, web-based other data management systems. these issues using will Clustal Omega, a Ireland industry research partnership award collaborative partners identifying opportunities interface extraction, querying interface thatfacilitates facilitates extraction, querying sequencing are facilitating proposals new programme recently described in in 2004.that The are now working totointegrate TheNIBRT NIBRTteam team are now working integrate and realising basic and applied research and sharing of HPLC-glycan data generated in and sharing of1000 HPLC-glycan data generated to human genomes Molecular Systems Biology, a scientific Thesequence Irish Times award recognises the stellarin GlycoExtractor with the EUROCarbDB GlycoExtractor with the EUROCarbDB synergies. This collaboration, initiated through high throughput processes. high throughput processes. (http://www.1000genomes.org) and in journal produced jointly by Naturehighand innovative performance of Sigmoid Pharma framework totoprovide aacomprehensive provide comprehensive highaframework SFI research supplement, highlights the 10,000 vertebrate genomes (http:// EMBO. their application of research and development. Glycosylation is the most common and throughput HPLC data analysis potential innovative indigenous companies Glycosylation theUCD most common and throughput HPLC data analysis platform for Meta-analysisisby researchers led by studies inthat humans have shownplatform that nonfor www.genome10k.org). Future scientific The company hasProfessor developed two new drughas the and annotation experimental structurally diverse post-translational working with academia canof realise.” Conway Fellow, Denis Shields progression was associated gross thestorage storage and annotation ofwith experimental structurally diverse post-translational technologies, and which studies mayof have to is compare 100,000s data. integration ofof next generation modification proteins. More than half ofofall Clustal can align any determined that there noSmPill™, clear evidence deletions in the nef gene. data.The TheOmega integration nextvirtually generation modification ofLEDDS™ proteins. More than half allnot Taylor’s collaboration with Sigmoid Pharmaand has only enhance the solubility andsequences permeability bioinformatic tools willsequences further thequickly gene products have been shown to behousein of of sequences and databases will number of protein that particular defective viral gene products have been shown to be bioinformatic tools will further the disease (CKD) and treatment, Conway researchers leditbytoDr. Tara locations certainly been bypatient these metrics with However, much of improve the research inOne the to the drug but can deliver targeted glycosylated. With many specific glycans or development ofsuccessful unified approaches for area millions of genome sequences. delivers accurate alignments. novel the HIV-1 nef gene or certain regions of the glycosylated. With many specific glycans or development unified approaches for McMorrow and Professor Ryan with particular focus on arising from three co-authored publications to date in date has beenof based onCKD observational or two caseof in the gastrointestinal tract,Michael including the have glycoforms potential asincancer handling large scale glycomics data initiatives protein playshowing a significant role disease aspect isand thehypertension. use vectors to reduce the glycoforms showing potential as in cancer handling large scaleof glycomics data initiatives diabetes The multisuccessfully secured €485,500 funding as the highest ranking scientific journals in the studies rather than rigorous, systematic colon. biomarkers, there is an increasing need to with applications in biomarker discovery progression. Modern approaches to aligning very large complexity of a key step in the algorithm, biomarkers, there is an increasing need to with applications in biomarker discovery disciplinary research consortium has 25of the part of an overall award to the Systems field, Gastroenterology andwork Proceeding scientific evaluation. This by doctoral develop high throughput, highly sensitive and numbers of patients sequences are starting toon dramatically reducing the processing The Sigmoid Pharma-Taylor collaboration is This research was partially supported develop high throughput, highly sensitive partners (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney National Academy Sciences, asout well as the HIV-infected can be categorised candidate Ravindra Pushker set toby robust strategies that detail the glycome ofand This research wasof partially supported become a bottleneck when facing such facilitating the development of a new time. the programme isbyto set robust strategies that detail the glycome from 15Currently, countries and the project due run Disease and Treatment generation of aproprietary innovative products the basisDiagnosis of the number of years it (SysKid) takes of for determine in substantially largerissample therapeutic approach for the treatment large data sets. are either fast of yet designed to align protein sequences and theassociation creation ofexists high-skilled jobs. for five years. consortium underThey theAIDS. European Union FP7 them to progress to Some patients if any between disease(not inflammatory bowel (IBD)counts by bringing maintain stable CD4 disease lymphocyte and progression and particular amino acid programme. More thanConway 15,000team, people in Ireland and The UCD together methodology themore do not gothe onresearch to develop AIDS even of after differences or deletionsincluding within thepostdoctoral nef gene. millions of people worldwide with the researchers Dr. Craig Slattery are andliving Dr. Natalia Syskid (www.SysKid.eu) was established to Taylor the proprietary than 10group yearswith of infection. symptoms IBD today. Current therapeutic On a per basis, there was no excess of liquid/emulsion drug delivery system,kidney Martin, willpatient utilise cell culture and animal further our understanding of chronic options for thiswith chronic diseasenef are Scientists developed are curiousby asSigmoid to why these longLTNP patients one debilitating or more defective LEDDS®, Pharma. Cell migration and invasion are critical infection inwhen the stomach. results in both academic outputs and the only Irish biopharmaceutical development very limited with surgery often being the term,research non- progressor (LTNP) patients do not sequences compared to progressors. most likely to die as a result of the raised New led by Conway Fellow Dr aspects of disease development whose Commenting onThis themay award, Professor Taylor application of The research toward product company, Sigmoid Pharma recently scooped viable option. Sigmoid currently develop AIDS. reflect differences in While the high frequency ofproduct, amino acid glucose levels inadiabetes. Breandán Kennedy indicates most likely die as result ofclinical raised New research ledsabotaged by Conway Fellow Dr actions be by treatment bacteria said, “Wecan are delighted forthe Drthat Coulter and at his Cortactin istoclinical aseen key regulator ofthe the actin development with indigenous companies.” the overall Innovation of Year award in a phase II study, uniquely host, viral genetics or environmental replacement at particular residues isenables indicative of diabetic blindness should look at glucose levels seen in diabetes. Breandán Kennedy indicates that treatment and viruses for own benefit. team and indeed ittheir reflects well on our for cytoskeleton often described as its Dr and team found new blood the inaugural Irish Times All-Island oral delivery of but ahis powerful drug that without factors that could potentially be exploited of Kennedy rapid evolvement, permutation testing protecting the neurons responsible of diabetic blindness should look atfor colour Commenting on the Taylor collaboration, Dr partnership. Aof key driver of successful Achilles heel because itcell seems prone to vessels and the neuronal death in diabetic Innovation Awards. The life-science SME, causing systemic side-effects. the treatment the disease. showed that residues with more replacements Dr Kennedy and his team found that new blood vision in the eye and notresponsible just targeting protecting the neurons for the colour Coulterby said, “The collaboration withofthe Taylor scientific research in 2010 is meaningful By targeting signalling factor proteins hijack pathogens keen todeath attack the retinopathy can arise independently each founded by UCD pharmacology graduate, Dr than expected were not statistically significant. vessels and the neuronal cell in diabetic blood vessels as is currently the practice. Glycomics needs the supporting framework cells, tissues and fluids. laboratory clearly demonstrates the potential vision in the eye and not just targeting the Understructure normal conditions, the gastrointestinal Studies in model organisms have shown that tasked with changes tothat the very theindependently cell. interaction of regulating academia with industry other. In addition, they identified that of cone Ivan Coulter, has actively collaborated with retinopathy can of arise each of extensive, well-curated databases and that be realised through focused blood vessels as is currently the practice. infection with nef-deficient virus an The can researchers conclude that current data scaffolding or cytoskeleton ofshows the cell, photoreceptor neurons, those involved in Nearly 2.5 million people worldwide are blind Conway Fellow, Professor Cormac Taylor Commercial packages that support HPLC other. In addition, they identified that cone flexible analytical tools. Currently, this field application of basic research. The development provides no evidence that individual residues attenuated course of infection and some bacteria and viruses can promote their The findings of this study, published colour visioncannot and used inthose daylight, are most due to being diabetic retinopathy. This Foundation secondary since granted a Science instruments facilitate the extraction photoreceptor neurons, involved in of Nearly million people worldwide are blind of study2.5 lacks the established, of a smart will depend on like-minded uptake into cells and sustain the recently thehigh Cell Host &alleviate Ireland industry research partnership award affected byineconomy the glucose levels. complication of diabetes activates the infective growth large quantities ofjournal data. In an effort to colour vision and used in daylight, are most due to diabetic retinopathy. This secondary comprehensive and centralised data collaborative partners identifying opportunities process by spreading further. Microbe, describe how Hp targets innew 2004. of leaky blood vessels in the eye and is this bottleneck within high-throughput affected bybythe high glucose complication of diabetes activates the growth collections, standards and information and realising basic and applied research The research team made theirlevels. observations cortactin two independent signalling responsible for the death of photoreceptors, glycomic projects, the NIBRT team have The Irish Times award recognises the stellar of new leaky blood vessels in the eye and is reporting protocols that exist within synergies. This collaboration, initiated through using a novel zebrafish of diabetes, A study led by send Professor Steffen pathways inweb-based order to model regulate gastric the neurons that visual messages to our developed a tool that interfaces The research team made their observations innovativeand performance ofofSigmoid Pharma in genomics proteomics. responsible for the death photoreceptors, a SFI research supplement, highlights the which resembles the early stages of diabetic Backert, UCD School of Biomolecular epithelial cell scattering and adhesion. brain. with thea Waters chromatography using novelinnovative zebrafish model ofsoftware diabetes, theirneurons application of research development. the thatScience send visual messages to our potential that companies retinopathy in humans. Itindigenous is an exciting & Biomedical andand involving package to improvethe and automate the export Researchers, Drhas Natalia Artemenko anddrug Dr which resembles early stages of hope diabetic The company developed two new working with academia can realise.” development for the group who now Until now, it was unclear if the changes to brain. researchers in Germany, Austria Professor Backert explains, “When Meta-analysis by UCD researchers led by studies in humans have shown that non to of data to various file formats for subsequent Matthew Campbell from the National Institute retinopathy in humans. It is an exciting technologies, LEDDS™ and SmPill™, which not further extend their research and establish a vessels and neurons occurred independently of and Spain proposes that&Denis the type-1 Hp targets it leads Conway Fellow, Professor Shields progression was associated withto gross analysis. Thecortactin, modular architecture ofPharma the tool of Bioprocessing Training (NIBRT) Taylor’s collaboration with Sigmoid has only enhance theResearch solubility and permeability development for the group who now hope to Until now, it was unclear if the changes to has model of late stage diabetic disease. one other and which type of retinal neuron is of carcinogen Helicobacter pylori (Hp) tyrosine dephosphorylation and serine determined that there is no clear evidence deletions in the nef gene. also facilitates manipulation of establish data from led Conway Fellow, Professor Pauline Ruddof certainly been the successful by these metrics with theby drug butneurons can deliver it to targeted locations further extend their research and a vessels and occurred independently targets the protein, cortactin in order phosphorylation. The phosphorylation that particular defective viral sequences other management systems. have developed an open access, web-based three co-authored to date in two in the gastrointestinal tract, the inis modeldata of late stage diabetic disease. one other and which type ofincluding retinal neuron However, much ofpublications the research the area to of to the gastric epithelium from status of cortactin dictates itsinsubcellular theprotect HIV-1that nef gene or certain regions of the interface facilitates extraction, querying the highest ranking scientific journals inorthe colon. date has been based on observational case excessive cell lifting androle ensure sustained The NIBRT team now working to integrate localisation andare signal transduction protein play significant disease and sharing ofa HPLC-glycan dataingenerated in field, Gastroenterology and Proceeding studies rather than rigorous, systematicof the GlycoExtractor with the EUROCarbDB The Sigmoid Pharma-Taylor progression. high throughput processes. collaboration is National Academy of Sciences, as as the scientific evaluation. work bywell doctoral framework to provide This a comprehensive highfacilitating the development of a new

most highly cited bioinformatics papers

“When we applied new drugs to our IBD Bioinformatic analysis of HIV progression studies ever. One of the these innovations of that model, the gut was tricked into thinking that it

Conway Award collaborator scoops Irish Kidney Times Innovation Award HRB Fellowship for Translational Disease Research Dr Higgins, UCD School of IrishDebra biopharmaceutical development Medicine & Medical Science, hasscooped company, Sigmoid Pharma recently been awarded a 4-year the overall Innovation of thePostdoctoral Year award at Fellowship Translational Medicine the inauguralin Irish Times All-Island from the Health Board. This Innovation Awards. Research The life-science SME, will allow her to further investigate founded by UCD pharmacology graduate, Dr Meta-analysis by UCD researchers by lysyl oxidase (LOX) proteins asled Ivan Coulter, has actively collaborated with Meta-analysis byProfessor UCD researchers led by Conway Fellow, Denis Shields potential biomarkers for early stage Conway Fellow, Fellow, Professor Professor Cormac Taylor has Conway Denis Shields has determined that there is no clear evidence kidney disease anda as a therapeutic since being granted Science Foundation determined that there is no clear evidence that particular defective viral sequences in target treatment chronic kidney Ireland for industry researchofpartnership award that particular defective viral regions sequences in the2004. HIV-1 nef gene or certain of the disease (CKD). in

In head-to head comparisons of the five Irish biopharmaceutical development therapeutic agents currently licensed in company, Sigmoid Pharma recently scooped Europe forInnovation the treatment of rheumatoid the overall of the Year award at arthritis (RA), differences in efficacy have the inaugural Irish Times All-Island been highlighted findings published Innovation Awards. in The life-science SME, in the Annals of the Rheumaticgraduate, Diseases. founded by UCD pharmacology Dr

Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields. renal injury biomarkers. Journal of Virology, Apr 2010 p3644-3653

Success in EU FP7 call

programme was that the algorithm was

was being deprived of oxygen. This activated designed to work on personal computers, protective pathways, which in turn prevented which greatly increased its the use among the death thecritical cells that line of HIV nefofare in determining the rate scientists. gastrointestinal tract,” explained Professor of disease progression. Professor Denis Taylor. pre-clinical trial dataforcan now of Shields“Our believes that searches modifiers Reference inform next phase Sigmoid Pharma progression rates should now focus on other Sievers Fthe et al. (2011) Fast, scalable generation ofproduct highmodels to identify processes involved in early development pipeline”. hostprogression and viral factors. “Systematic evaluation quality protein multiple alignments using CKD andsequence investigate novel Clustal Omega. Molecular Systems Vol. 1 of large quantities of data by Biology, bioinformatics strategies the7, No. In additionfor to preventing the productand thatslowing is currently in msb.2011.75. can be just of as the important inThese refuting progression disease. studies will phaseresearchers II clinicalDrstudies, Pharma is NIBRT MatthewSigmoid Campbell and Dr Natalia hypotheses that current inepidemiological theand literature, as NIBRT researchers Matthew Campbell Dr Natalia be integrated withDrare clinical and Artemenko who GlycoExtractor developing a developed LEDDS™-enabled formulation of Higgins DG, Sharp PM (1988). “CLUSTAL: a package it is in discovering unknown patterns”, he said. Artemenko who developed GlycoExtractor studies across the consortium using systems the hydroxylase inhibitor for performing multiple sequence alignment on a biology methodologies in order to new microcomputer”. Gene (1): 237–244 dimethyloxaloylglycine (DMOG) todevelop bring about This research was 73 funded through Science diagnostic strategies andUniversity treatment options effective, safe and targeted deliveryCollege of this to Foundation Ireland and prevent development. potential therapeutic agent.Email Dublin.CKD tara.mcmorrow@ucd.ie for details of a PhD position currently available.

Conway collaborator Irish Times Award Zebrafish gives insights into diabetic Helicobactor Pylori Target Keyscoops Regulator ActinInnovation Cytoskeleton Zebrafish model model gives insights into diabeticofblindness blindness

partners. These changes to Dr theKennedy tract is lined with cells that block the contents Commenting on the research, amino acid structure of the Reference: of the gut from leaking into the protein intestine. In an Commenting on the research, Dr Kennedy said, “By establishing a robust of model for early Meta-analysis to test the association HIV-1 nef amino consequently onbroken the regulation IBD patient, thisimpact barrier is and the and late stage diabetic retinopathy, we would said, “By establishing a robust model for early acid differences and deletions with disease progression. of gastric epithelial cell scattering and contents of the gut leak out into surrounding Ravindra Pushker, Jean-Marcretinopathy, Jacquē, Deniswe C. Shields. hope to better understand the progression of and late stage diabetic would adhesion.” areas. research in UCD Conway used JournalThe of Virology, Aprteam 2010 p3644-3653 the disease and understand pave the way forprogression identifying of hope to better the a model of IBD and, by applying a new class of EUROCarbDB, a research infrastructure design new targets for its successful treatment”. the drug disease and pave the way foris identifying The gene encoding cortactin amplified drugs known as hydroxylase inhibitors, were study funded by the EUits6th Framework in some human cancers and scientists new drug targets for successful treatment”. able to almostwas completely reverse the The research funded users through Programme. Prospective canScience suspect that thedisease. protein plays a access major the symptoms of the Foundation Ireland and the through Health Research GlycoExtractor tool on The research was funded role in tumour invasion. BackertScience and Board. http://glycobase.nibrt.ie:8080/DemoGlycoExtra “When we hope applied drugs to our IBD Foundation Ireland and new the Health Research his team tothese investigate in future ctor/mainPage. model, gutHp-mediated was tricked intodisruption thinking that studies how of it Board.the was being deprived of oxygen. activated Reference signalling to cortactin couldThis contribute Reference: A of web-based interface for high GlycoExtractor: protective pathways, which in turn prevented to the onset gastric cancer. Predominantprocessing dysfunction of HPLC-Glycan throughput the death ofcone thephotoreceptor cells that line thedata in a Reference: hyperglycaemic modelMatthew of non-proliferative V. Artemenko, P. Campbell,diabetic and Pauline Natalia gastrointestinal tract,” explained Professor Reference Predominant cone photoreceptor dysfunction arate retinopathy. Alvarez,in Jenneth Chen, Alison M. Rudd ofcritical Proteome Research, 2010, 9in(4), pp of HIV Journal nefYolanda are determining the Tegtmeye N et al. Serine Phosphorylation of Cortactin Taylor. “Our pre-clinical trial data can now hyperglycaemic model of non-proliferative diabetic 2037–2041 Reynolds, Noreprogression. Waghorne, JohnProfessor J. O’Connor, Breandan of disease Denis Controls Focal Adhesion Kinase Activity and Cell inform the next phase Sigmoid product retinopathy. Yolanda Alvarez, JennethPharma Chen, Alison Kennedy. Disease Models &searches Mechanisms (2010) Shields believes for modifiers Scattering bythat Helicobacter Cell Breandan Host & of Reynolds,Induced Nore Waghorne, John J.pylori. O’Connor, development progression pipeline”. rates should now focus on other

GlycoExtractor advances glycan data manipulation

Bioinformatic analysis of HIV progression studies

Microbe 9,520–531,June Kennedy. Disease Models16&2011 Mechanisms (2010)

and viral factors. “Systematic evaluation Inhost addition to the product that is currently in of large quantities of data by bioinformatics phase II clinical studies, Sigmoid Pharma is can be justaas important in refuting developing LEDDS™-enabled formulation of hypotheses that are current in the literature, as


Conway Focus Issue 15 Autumn 2011