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