leading to mitotic arrest and ultimately
Commenting cell death. on the Taylor collaboration, Dr Coulter said, “The collaboration with the Taylor The Participate programme focused on laboratory clearly demonstrates the potential Ivan Coulter,of has actively collaborated with Dr McGee and postgraduate student, advanced treatment regimens for RA in the Department Rheumatology in St Vincent’s that can be realised through focused May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3 Fhearraigh Conway Fellow, Professor Cormac Taylor Sean looked atdevelopment molecular clinic,Mac including practical aspects of biologic application of basic research. The University Hospital was chosen to host an New research led by Conway Fellow, since being granted a Science Foundation signals that connect cell cycleonarrest therapy carried out in the accredited infusion of a smart economy will depend like-minded Dr Margaret McGee suggests that international two-day workshop on March Ireland industry research partnership award to thethat cellprovides death machinery chronic collaborative partners identifying opportunities suite optimal careinfor RA an important cell death signal in 2004. 26th & 27th 2010. Sponsored by Roche myeloid leukaemia (CML) cells. and realising basic and applied research patients. In addition to lectures from Conway during mitotic arrestthe stellar The Irishprolonged Times award recognises Pharma, the Participate workshop gave synergies. This collaboration, initiated through is the Cdk1/cyclin B1-dependent Fellows, Professors Oliver FitzGerald and innovative performance of Sigmoid Pharma in a SFI research supplement, highlights the Explaining theirdelegates findings,heard Dr McGee said, twenty rheumatologists of from centres in hyperphosphorylation the Douglas that Veale, from clinical their application of research and Bcl-2 development. potential innovative indigenous companies “Cell cycle progression is controlled by Europe and Australia the opportunity to interacting of celltwo death The companymediator has developed new (Bim). drug nurse specialists aboutcan patient education, working with academia realise.” various cyclins and cyclin-dependent technologies, LEDDS™ and SmPill™, which not witness the care of patients with rheumatoid screening and monitoring of biological kinasescollaboration (Cdks) and our reveals has Taylor’s withresearch Sigmoid Pharma only enhance solubility and permeability of Research hasthe highlighted a crucial therapies. arthritis (RA) at St Vincent’s. that these kinases can also control cellwith certainly been successful by these metrics the drug but can deliver it to targeted locations role for Bim in paclitaxel (Taxol®)three publications to date in two of deathco-authored through the direct phosphorylation in the gastrointestinal tract, including the mediated death of tumour cells. This the highest ranking scientific journals in the colon. field, Gastroenterology and Proceeding of the The Sigmoid Pharma-Taylor collaboration is National Academy of Sciences, as well as the facilitating the development of a new generation of proprietary innovative products therapeutic approach for the treatment of and the creation of high-skilled jobs. inflammatory bowel disease (IBD) by bringing More than 15,000 people in Ireland and together the research methodology of the millions of people worldwide are living with the Taylor group with the proprietary symptoms IBD today.inCurrent liquid/emulsion An image of thedrug frogdelivery peptidesystem, structure central variety of solutions order totherapeutic understand the options for this chronic debilitating disease are LEDDS®, developed Sigmoid Pharma.team to the work of a UCDbyConway research structural basis for the difference in biological limited with surgeryoutcome often being the results in both academic outputs and the only Irish biopharmaceutical development Senior Research Fellow, Dr Darran avery significantly poorer when was selectedon asthe theaward, front cover image for the Commenting Professor Taylor activity. viable option. Sigmoid product, currently application of The research toward clinical product company, Sigmoid Pharma recently scooped O’Connor received the 9th St Luke’s treated with tamoxifen compared to said, “We delighted forscientific Dr Coulter and his April 2010are edition of the journal, in a phase II clinical study, uniquely enables development withwith indigenous companies.” the overall Innovation of the Year award at Young Investigator award from the those patients zero or low levels Thisdelivery particular peptide, isolated from the team and indeed it reflects well our Biochimica etIrish Biophysica Actaon (BBA); oral of aXT-7 drug the inaugural Times Royal Academy of Medicine in Ireland of the protein. Inpowerful the future, itwithout may be partnership. A key driver ofAll-Island successful skin of systemic Silurana tropicalis, shows potential Commenting on the Taylor collaboration, Dr for causing side-effects. Proteins & Awards. Proteomics. Innovation The life-science SME, for ‘Antibody based proteomics: Fast possible to establish the CART status of scientific research in 2010 is meaningful Coulter said,cancer “The collaboration with the activity Taylor drug development as it has impressive founded by UCD pharmacology graduate, Dr tracking molecular diagnostics in a patient’s in order to personalise Under normal conditions, the gastrointestinal interaction academia with industry Peptides inofthe skin of many species that of frog
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 B1 during mitosis thatoutmediates the contents of the gut leak into surrounding phosphorylation Bim Cdk1. areas. The research of team in by UCD Conway used a Addressing model of IBD by applying a newMs class of theand, international guests, Mary drugs known as inhibitors, We that hyperphosphorylation Duff,believe Director ofhydroxylase Nursing and Ms. Kay were able to almost completely reverse theCdk1 of Bim resulting from sustained Connolly, Assistant Director of Nursing for the symptoms of the disease. activity during mitotic arrest may be
Bone & Joint Unit expressed their hope that
an important molecular that “When we applied newswitch drugs to our IBD the experience ofthese the multidisciplinary team promotes cellwas death during mitotic that arrest. model, the gut tricked into thinking it from St Vincent’s would provide a template for was being deprived of oxygen. This activated delegatespathways, to reproduce similar care and protective which in turn prevented the death of that line the facilities forthe thecells management of RA patients in Reference: gastrointestinal tract,” explained Professor their respective countries. Mac Fhearraigh et al. cyclintrial B1 interacts with Taylor. “Our pre-clinical data can now the BH3-only protein BimSigmoid and mediates its product inform the next phase Pharma phosphorylation by Cdk1 during mitosis. Cell Cycle development pipeline”. 10:22, 3886-3896; November 15, 2011 In addition to the product that is currently in phase II clinical studies, Sigmoid Pharma is developing a LEDDS™-enabled formulation of the hydroxylase inhibitor dimethyloxaloylglycine (DMOG) to bring about effective, safe and targeted delivery of this potential therapeutic agent.
Frog peptide structure selected for journal cover Awards for research excellence Conway collaborator scoops Irish Times Innovation Award
oncology’. Ivan Coulter, has actively collaborated with
have anti-bacterial and anti-fungal properties Conway Fellow, Professor Cormac Taylor 13:12 May 2010.qxd:Layout copy 07/05/2010 as well as the1ability to lyse or rupture sinceisbeing granted a Science This based on research of aFoundation protein mammalian cells. This innate immunityaward Ireland industry research partnership named cocaine-and-amphetamineprotects attack.(CART), These properties of in 2004. it from regulated transcript a potential frog skin peptides are exciting from the breast cancer biomarker, by the SFIThe Irish Times award recognises the stellar prospectstrategic of being developed into funded research cluster, innovative performance of Sigmoid Pharma in therapeutically valuable anti-infective and antiMolecular Therapeutics for Cancer their application of research and development. Meta-analysis by UCD researchers led by cancer agents. Ireland. Dr O’Connor and his The company has developed twocolleagues new drug
laboratory demonstrates the Candida potential against theclearly growth of bacteria and their treatment regimen. that can beHowever, realised through focused albicans. this potential as an antiPage 3
application of basic research. The development PhD student, Salunkhe a infective agentVishal is restricted by itsreceived haemolytic of a smart economy will depend on like-minded $500 abstract achievement award at the activity. collaborative partners identifying opportunities 53rd American Society of Haematology and realising and applied research A change to basic theconference amino acid in structure of the (ASH) annual San Diego. synergies.with This Dr collaboration, initiated Vishal through Working Patricia Maguire, XT-7 peptide can create an analogue that a SFI research supplement, factor highlights the focuses on transcription retains in anti-infective properties butMEIS1, without the studies humans have shown that non potential that innovative indigenous companies an important molecular switch from complicating haemolytic The single progression associated with gross working with was academia canactivity. realise.” megakaryocyte to pro-platelet formation. deletions in 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.
“When we applied these new drugs to our IBD Bioinformatic analysis of HIV progression studies model, the gut was tricked into thinking that it
Conway Fellow, Professor Denis Shields has examined breast cancer tissue in over technologies, LEDDS™ and which not determined that there is noSmPill™, clear evidence Conwaypatients. Fellow, Dr Chandralal Hewage and his 1,000 They found that those that particular defective viral sequences in of only enhance the solubility and permeability team carried out molecular modelling of the patients with high CART had the drug HIV-1but nefcan gene orlevels certain regions of the deliver it tooftargeted locations
XT-7 peptide its analogue [G4K]XT-7 in a protein play aand significant in disease in the gastrointestinal tract,role including the progression. colon.
HIV-infected patients can be categorised on The Sigmoid Pharma-Taylor collaboration is the basis of the number of years it takes for facilitating the development of a new them to progress to AIDS. Some patients therapeutic approach for the treatment maintain stable CD4 lymphocyte countsofand inflammatory bowel disease (IBD) bringing do not go on to develop AIDS evenby after more together the research methodology of the than 10 years of infection. Irish biopharmaceutical development Two research associated with Taylor group withgroups the proprietary Scientists are curious as to why thesescooped longcompany, Sigmoid Pharma recently the Institute have recently reported liquid/emulsion drug delivery system, A new fortnightly forum for graduate term, non- progressor patients do at not the overall Innovation (LTNP) of theConway Year award research findings in Nature journals. LEDDS®, developed by Sigmoid Pharma. and postdoctoral researchers will be launched develop AIDS. Irish This Times may reflect differences in the inaugural All-Island in May This will give earlythe host,2010. viral genetics environmental Innovation Awards. Theorlife-science SME, Commenting on theinitiative award, Professor Taylor Conway Fellow, Dr Teeling led factors that could potentially exploited for founded by UCD pharmacology graduate, Dr stage“We researchers theEmma opportunity to talk said, are delighted for DrbeCoulter andabout his the treatment of only the disease. Ivan Coulter, has actively collaborated with ateam study on the two populations science and issues that concern them and indeed it reflects well on our in an Conway Fellow, Professor Cormac Taylor in existence the world’s smallest informal with Studies inenvironment model organisms have shown that partnership. Aof key driver of refreshments successful since being granted a Science Foundation mammal, the bumble bee bat, to 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 of infection and some determine early drivers at play in interaction ofthe academia with industry that in 2004. course
amino acid substitution (glycine replaced by Taylor’s collaboration with Sigmoid Pharma has lysine) improves of However, much ofthe thetherapeutic research inpotential the area with to certainly been successful by these metrics date has been occurring based on observational or case this naturally peptide. three co-authored publications to date in two of studies rather than rigorous, systematic the highestevaluation. ranking scientific journals in the scientific This work by doctoral field, Gastroenterology and Proceeding candidate Ravindra Pushker set out to of the National Academy of Sciences, as well as the determine in a substantially larger sample set generation of proprietary innovative products if any association exists between disease and the creation high-skilled jobs. progression andof particular amino acid
was being deprived of oxygen. This activated protective pathways, which in turn prevented Dr James Jones, IJMS; of HIV nef critical in determining theWalsh, rate the death ofare theeditor-in-chief cells that line theProf Tom past president RAMI; Dr Darran O’Connor,Denis winner of of disease progression. Professor gastrointestinal tract,” explained Professor the 9th St Luke’s Young Investigators award; Dr Ken Shields“Our believes that searches modifiers Taylor. pre-clinical trialRAMI dataforcan now of O’Halloran, general secretary progression rates should now focus onproduct other inform the next phase Sigmoid Pharma Coverand of April edition“Systematic of Biochimica evaluation et Biophysica host viral2010 factors. development pipeline”. Acta (BBA); Proteins & Proteomics.
of large quantities of data by bioinformatics be justtoasthe important refuting Incan addition product in that is currently in hypotheses thatstudies, are current in thePharma literature, phase II clinical Sigmoid is as it is in discovering unknown patterns”, he said. developing a LEDDS™-enabled formulation of
Conway scoops Irish Times In brief:ofResearching the small Nature Launch Conwaycollaborator postdoctoral &ingraduate forumInnovation Award
the evolution of a species. Teeling and The Irish Times award recognises the stellar her team were in the unique position innovative performance of Sigmoid Pharma in of being able tooflook at speciation their application research and development. Theaction’ company has developed two new drug ‘in and found that geological technologies, and SmPill™, which not distance hasLEDDS™ a primary role in limiting
differences or deletions within the nef gene.
More than 15,000 people in Ireland and On a per basis, was no excess of results inofpatient both academic outputs and the gene flow rather thanthere echolocation millions people worldwide are living with the LTNP patients with one or more defective nef application of research toward clinical product divergence. symptoms IBD today. Current therapeutic decided by the members but it is envisaged sequences when progressors. development with compared indigenoustocompanies.” options for include this chronic disease are that itthe will a mixdebilitating of While high frequency of technology amino acid very limited with surgery often being the only Commenting on the Taylor collaboration, Dr With the possibility that nanoparticles overviews, informal and formal research replacement at particular residues is indicative Coulter said, “The collaboration with the Taylor viable option. The Sigmoid currently could offer new ways to product, deliver drugs of rapid evolvement, permutation testing seminars, PhD viva rehearsals and career laboratory clearly demonstrates the potential in a phase II clinical study, uniquely enables showed that residues with more replacements into thebe body, Professor Kenneth development talks from within and beyond that can realised through focused oral delivery of were a powerful drug without than expected not statistically significant. Dawson’s team explore theThe fate of these academia. of Forum committee members, PhD application basic research. development causing systemic side-effects. student Mreconomy Thomas Schwarzl miniscule materials independ cells. Their recent The researchers conclude that current data of a smart will on like-minded provides no evidence thatthe individual residues collaborative partners identifying opportunities Under normal conditions, gastrointestinal findings show that nanoparticles are not and realising basic andbut applied research exported from cells are split between synergies. This collaboration, initiated through daughter cells when the parent cell a SFI research supplement, highlights the divides. that A cell that divides frequently will potential innovative indigenous companies dilute the with each working withnanoparticle academia candose realise.”
the hydroxylase inhibitor This research was funded through Science dimethyloxaloylglycine to bring about Foundation Ireland and(DMOG) University College Dublin. safe and targeted delivery of this effective, potential therapeutic agent. tract lined with cells that block thethrough contents cell isvaries as the cell advances
ofthe thevarious gut fromphases leakingof into the intestine. theand cell cycle. In an (thomas.scharzl@ucd.ie postdoctoral IBD patient, this barrier is )broken and the researchers, Dr David Gomez Reference: Reference: contents of the gut leak out into surrounding Meta-analysis tooftest association ofCraig HIV-1uptake nef amino (david.gomez@ucd.ie) and Dr Slattery Kim et The al. Role cellthe cycle cellular and areas. research teamon inthe UCD Conway used acid differences and deletions with disease progression. dilution cell population aRavindra modelof ofnanoparticles IBD and, byinapplying a new of (craig.slattery@ucd.ie )aJacquē, invite suggestions for Pushker, Jean-Marc Denis C. class Shields. Nature Nanotechnology (2012) doi:10.1038/ drugs known as hydroxylase inhibitors, were Journal of Virology, Apr 2010 p3644-3653 the forum schedule. nnano.2011.191 able to almost completely reverse the symptoms of the disease. Puechmaille et al. The evolution of sensory “When we applied theseofnew drugs our divergence in the context limited geneto flow in IBD model, the gutbat was tricked into thinking(2011) that it the bumblebee Nature Communications was being deprived of oxygen. This activated doi:10.1038/ncomms1582 protective pathways, which in turn prevented the death of the cells that line the gastrointestinal tract,” explained Professor Taylor. “Our pre-clinical trial data can now inform the next phase Sigmoid Pharma product development pipeline”.
cycleHIV of cell division. The dose in each studies Bioinformatic analysis of progression Taylor’s collaboration with Sigmoid Pharma has
only enhance the solubility and permeability of the drug but can deliver it to targeted locations in the gastrointestinal tract, including the colon.
Meta-analysis by UCD researchers led by
The Sigmoid Pharma-Taylor collaboration Conway Fellow, Professor Denis Shields is has facilitating development a new determinedthe that there is noof clear evidence therapeutic approach for the of in that particular defective viraltreatment sequences inflammatory disease (IBD) by bringing the HIV-1 nef bowel gene or certain regions of the together the research methodology of the protein play a significant role in disease Taylor group with the proprietary progression. liquid/emulsion drug delivery system, LEDDS®, developed Pharma.on HIV-infected patients by canSigmoid be categorised
Investing in Your Future
the basis of the of years it takes for Commenting on number the award, Professor Taylor them “We to progress to AIDS. patients said, are delighted for Some Dr Coulter and his team and stable indeedCD4 it reflects well on our and maintain lymphocyte counts partnership. driver AIDS of successful do not go onAtokey develop even after more scientific research in 2010 is meaningful than 10 years of infection. interaction of academia with industry that Scientists are curious as to why these longterm, non- progressor (LTNP) patients do not
certainly been successful by these metrics with three co-authored publications to date in two of the highest ranking scientific journals in the studies in humans haveand shown that nonof the field, Gastroenterology Proceeding progression was associated with National Academy of Sciences, as gross well as the deletions inofthe nef gene.innovative products generation proprietary and the creation of high-skilled jobs.
In addition to the product that is currently in of HIVIInef are critical in Sigmoid determining the rate phase clinical studies, Pharma is of disease aprogression. Professor Denis of developing LEDDS™-enabled formulation Shields believesinhibitor that searches for modifiers of the hydroxylase Elaine Quinn progression rates should now focus on about other dimethyloxaloylglycine (DMOG) to bring Communications & Education However, much of the research in the area to effective, targeted delivery of thisOfficer host andsafe viraland factors. “Systematic evaluation More than 15,000 people in Ireland and date has been based on observational or Conway case UCD Institute of quantities Biomolecular & Biomedical Research potential therapeutic of large ofagent. data by bioinformatics millions of people living with the studies rather thanworldwide rigorous, are systematic University College Dublin can be just as important in refuting symptoms IBD today. Current therapeutic scientific evaluation. This work by doctoral Dublinas4 hypotheses that are current inBelfield, the literature, options for this chronic debilitating disease are candidate Ravindra Pushker set out to Ireland it is in discovering unknown patterns”, he said. very limited with surgery often being the only determine in a substantially larger sample set viable option. The Sigmoid product, currently E: elaine.quinn@ucd.ie if any association exists between disease This research was funded through Science in a phase II clinical study, uniquely enables T: (+353-1) 716 6706 progression anda powerful particulardrug amino acid Foundation Ireland and University College oral delivery of without F: (+353-1) 716 6701 differences or deletions within the nef gene. Dublin. causing systemic side-effects.
On a per patient basis, there no excess of Under normal conditions, the was gastrointestinal LTNP patients with one or more defective nef sequences when compared to progressors.
W: www.ucd.ie/conway
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. the NIBRT team have reporting protocols that exist within development glycomic projects, results in bothtool academic outputs and the Referencetract is lined with cells that block the contents Irish biopharmaceutical developed a web-based that interfaces Research by Conway Fellow, Dr Oliver the function of worm Arl13b causes the complex traits including obesity, diabetes, research has just taken a and distant metastases respectively. growth factor receptor (EGFR), which GlycoExtractor: web-based interface for high genomics and Cancer proteomics. of theAgut from leaking into the intestine. In an application of research toward clinical product company, Sigmoid Pharma recently scooped with the Waters chromatography software throughputmental processing of HPLC-Glycan data cancer. Blacque has revealed new information ciliary membrane to bulge and become retardation and even new twist. K-Ras, one of the most requires the wild-type (WT) K-Ras allele. patient,Matthew this barrier is broken and the indigenous companies.” Natalia V. IBD theNatalia overallArtemenko Innovationand of the at to development improve andwith automate the export Researchers, Dr Dr Year awardpackage Artemenko, P. Campbell, and Pauline about a gene implicated in Joubert misshapen as as affecting the ability M. of Rudd Journal frequently genes in human With the MST2 expression, late stage Describing thewell research, Dr David contents ofloss the of gutResearch, leak out into surrounding the inaugural Irish Times All-Island of Proteome 2010, 9 (4), pp Matthew Campbell from the mutated National Institute of data to various file formats for subsequent Dr Oliver Blacque hopes that these findings Commenting on the Taylor collaboration, Dr 2037–2041 syndrome related disorders other proteins to properly distribute areas. Thedo research team inprotective UCD Conway used Innovation Awards. The life-science SME, cancer, isand known as cerebellar an oncogene that The tumours not require function Matallanas, group leader in Systems analysis. modular architecture of the tool thewithin of Bioprocessing Research & Training (NIBRT) Coulter said, “The collaboration with Taylor will ultimately lead to a greater aofmodel of processes IBDallele and, and byinvolved applying founded bycharacterised UCD Drfacilitates models to identify ina new earlyclass of (CKD) and improve patient treatment, Conway researchers by Dr.pharmacology Tara (JSRDs), byRudd blindness, bone the ciliary membrane. led by Conway Fellow,led Professor Pauline also the manipulation of data from drives the development ofgraduate, manydisease WT K-ras EGFR. Biology Ireland said, “We were able to show laboratory clearly demonstrates the potential understanding not only ofnovel JSRDs, butwere also drugs known hydroxylase inhibitors, Ivan Coulter, hascystic actively collaborated with particular CKD progression andasinvestigate have developed an open access, web-based other data management systems. McMorrow andabnormalities, Professor Michael Ryan haveNow,with kidneys, on CKD arising from prevalent human cancers. Patients with Dukes’ A stage CRC are thatfocus the ability to activate MST2 is specific that can be realised through They also found that a fullyfocused functional offor closely related ciliopathies such able topreventing almost completely reverse the as Conway Fellow, Professor Cormac Taylor interface that secured facilitates extraction, querying strategies and slowing the developmental delay and loss of muscle diabetes and hypertension. The multisuccessfully €485,500 in funding as application of basic research. The development research unveiled an inunexpected successfully treated with surgerysyndrome, alone. to K-Ras and when K-Ras The NIBRT Arl13b team are now that working to mutant integrate symptoms of the disease. since beinghas granted a Science Foundation protein is needed for the normal Meckel Gruber and Bardet-Biedl and of tone HPLC-glycan dataSystems generated progression of the disease. These studies will and control. The findings of this disciplinary research consortium 25 pathway, of a with smartthe economy willhas depend on like-minded partsharing of an overall award to non-mutated the GlycoExtractor EUROCarbDB face ofindustry the K-Ras as However, 20-30% of Dukes’ B stage patients activates the MST2/LASTS1 the Ireland research partnership award high throughput processes. functioning of a protein transport system in as well as perhaps more common be integrated with clinical and epidemiological “When we applied these new drugs to our IBD collaborative partners identifying opportunities research, funded of through a Science partners (16to universities, 9 industry partners) Biology towards Novel Chronic Kidney framework provide a comprehensive highin 2004. an accomplice the mutant K-Ras relapse andconsortium perhaps these patients may downstream effector istransport the tumour cilia. This intraflagellar system studies across phenotypes associated with model, was tricked intocilium thinking that it and realising basic and applied research the gut using systems throughput HPLC data analysis platform for Glycosylation is the most common and Foundation Ireland President of Ireland from 15 countries and the project is due to run Disease Diagnosis and Treatment (SysKid) The Irish Times award recognises the stellar oncogene. benefit from EGFR therapeutic suppressor protein, p53. (IFT) makes contact with the ciliary dysfunction such as mental retardation and was being deprived ofinhibitory oxygen. This activated synergies. This collaboration, initiated through biology methodologies in order to develop new structurally diverse post-translational the storage and annotation of experimental Young Researcher Award (PIYRA) to Oliver for five consortium under the European Union FP7 innovative performance of Sigmoid Pharma in years. regimens”. protective pathways, which inoptions turn prevented amembrane. SFI research supplement, highlights on these results, the they diagnostic obesity. modification proteins.were Morerecently than halfpublished of all of Based next generation strategies and treatment to in data. the The integration programme.ofBlacque, their application of research and development. the death of the cellsEmail that line the potential that innovative indigenous companies of research Using genetically engineered cell system, gene products The havefindings been shown to be published recently bioinformatic toolsa will further the The UCD Conway team, including postdoctoral proposed a new working model for Arl13b, prevent CKD development. The company hasBiology. developed two new drug Journal of Cell He notes “Thatwas Arl13b associates with funding ciliary gastrointestinal tract,” explained Professor working academia can realise.” glycosylated. With many specific glycans or development ofwere unified approaches for in Molecular Cell demonstrate mutant This research we able to corroborate that the WT researchers Dr. Craig Slattery and Dr. Natalia Syskid (www.SysKid.eu) was established to thatwhich where itwith functions at the ciliary membrane tara.mcmorrow@ucd.ie for supported details of athrough PhD technologies, LEDDS™ and SmPill™, not Taylor. “Our pre-clinical trial data now membranes and is required forcan cilium glycoforms showing potential as cancer handling large scale glycomics data initiatives K-Ras transformation is supported theof will Martin, utilise cell culture and animal position currently available. further our understanding chronic kidney from Science Foundation Ireland, Cancer K-Ras counteracts the proapoptotic effects One sevenofthe genes associated with by JSRDs, to regulate important ciliary membrane Taylor’s collaboration with Sigmoid Pharma has only of enhance solubility and permeability inform the next phase Pharma with applications in been biomarker discovery biomarkers, there is an increasing need to structure/function in Sigmoid both worms andproduct certainly successful by transmembrane these metrics with the drug but can it to already targeted locations Arl13b codes fordeliver protein known to properties such as shape, wild type allele ina colorectal carcinoma Research UK,pipeline”. EU Campbell FP6 STREP Growthstop, of mutant K-Ras”. development NIBRT researchers Dr Matthew and Dr Natalia develop high throughput, highly sensitive and mammals demonstrates the remarkable three co-authored publications to date in two of in theroles gastrointestinal tract, including theThis research was partially supported by play in the and/or function protein distributions and IFT. ArtemenkoKuwait who developed GlycoExtractor (CRC). Foundation for the Advancement of robust strategies that detail the formation glycome of evolutionary conservation ofishow this small In addition to the product that currently in the highest ranking scientific journals in the colon. of cilia, which are hair-like projections Sciences, Research Core Facility. Given that KRAS is commonly mutated phase II clinical studies, Sigmoid Pharma is field, Gastroenterology and many Proceeding of the Up to only 20 years ago, believed G-protein functions.” extending from the of the cell. The Sigmoid Pharma-Taylor is RAS mutations aresurface seen incollaboration more than 30% in colorectal carcinoma (CRC), the as team developing National Academy of Sciences, as well the Reference: a LEDDS™-enabled formulation of most cilia to be redundant cellular facilitating the development of aKRAS new However, precise details of Reference of humanthe cancers, ofmolecular which looked at KRAS gene mutations and MST2 the hydroxylase inhibitor generation of proprietary innovative products organelles that have fallen victim to Matallanas et al. Mutant Activation of the therapeutic approach for the treatment of Joubert syndrome Arl13b K-Ras functions what exactlyaccount Arl13b is cilia have dimethyloxaloylglycine (DMOG) at tociliary bring about and the creation of high-skilled jobs. mutations fordoing aboutin85%. K-Ras protein expression in 173 CRC patients. Proapoptotic MST2 Pathway Is Antagonized mammalian evolution a type of cellular membranes and stabilizes protein transport inby Wildinflammatory bowel disease (IBD) by bringing cells, tissues and fluids. EUROCarbDB, a research infrastructure design Glycomics needs the supporting framework effective, safe and targeted delivery of this remained unclear. protein only family member Theirthan findings indicate WT K-Ras allele Type K-Ras. Molecular 44,S,893–906, December More 15,000 people inthat Ireland and Caenorhabditis elegans.Cell Cevik Hori Y, Kaplan OI, appendix. We now knowthat these cellular together is thethe research methodology of that the can potential therapeutic agent. study funded by the EU 6th Framework of extensive, well-curated databases and 23, activate apoptosis. Kida2011 K, Toivenon T, Foley-Fisher C, Cottell D, Katada T, ispackages critical for anti-apoptotic signalling. millions ofpresent people worldwide are living with the that support HPLC Taylortools. group withstudied the proprietary Blacque’s team thefield gene in theCommercial cilia antennae on nearly allEGFR of our cellsProgramme. flexible analytical Currently, this Prospective users can access the Commenting research, DrBiol. Kennedy likely symptoms tocannot die as aIBD result of raised retained, New research liquid/emulsion led by Conwaydrug Fellow Dr system, most Kontanion K, the Blacque OE. J Cell 2010 Mar 22; Current delivery Unless the WTtoday. K-ras allele MST2 instruments facilitate thethe extraction of of worms (Caenorhabditis elegans) and serve rolesistherapeutic in many of study lacks thetiny established, GlycoExtractor tool ona robust glucose levels seen infundamental diabetes. Breandán Kennedy indicates that by treatment said, “By188(6):953-69 establishing for early positive weakmodel positive negative options for this chronic debilitating disease are LEDDS®, developed Sigmoid Pharma. large quantities of data. In an effort to alleviate Led by Professor Walter Kolch, Director, expression and K-Ras mutations cannot while inatthe University of motility andwith sensory functions, including comprehensive and collaborators centralised data http://glycobase.nibrt.ie:8080/DemoGlycoExtra of diabetic blindness should look and late stage diabetic retinopathy, we would very limited surgery often being the only Dr Kennedy and his team found that new blood this bottleneck within high-throughput Systems Biology Ireland &Professor UCD Conway co-exist. Commenting on theparallel award, Taylor Tokyo conducted experiments in 13:12 viable signalling critical to development. protecting the neurons responsible for07/05/2010 colour collections, standards and information ctor/mainPage. May 2010.qxd:Layout 1 copy Page 3pathways hope to better understand the progression of option. The vessels the neuronal cellSigmoid death inproduct, diabeticcurrently glycomic projects, the NIBRT team have said, “We are delighted for Dr his and Institute, this international research vision in the eye and not just targeting theCoulter cultured human cells. Together, theyand reporting protocols that exist within disease and pave the way for identifying incan a phase II clinical study,of uniquely enables the Reference retinopathy arise independently each It isMatallanas now notoftool surprising that defects developed aoral that interfaces team indeed it reflects well onuses ourK-Ras blood vessels as is and currently the practice. collaboration that mutant Drweb-based “When ourinCRCnew delivery aexplains, powerful drug without GlycoExtractor: A web-based for high drug targets for its interface successful treatment”. thatreports Arl13b proteins lipid genomics and confirmed proteomics. other. In Waters addition, they identified that cone with the chromatography software cilium structure and function areaccording associated partnership. A key driver of successful processing of HPLC-Glycan data throughput causing systemic side-effects. binds directly to the tumour suppressor patient cohort was subdivided to research anchors to associate with the ciliary photoreceptor neurons, those involved in Nearly 2.5researchers million people worldwide are Dr blind models to identify processes involved in early and improve patient treatment, Conway led by Dr. in Tara The was funded through Science scientific research 2010 is meaningfuldisease Researchers, Dr Natalia Artemenko and package(CKD) to with improve and automate the export Natalia V. Artemenko, Matthew P. Campbell, and Pauline an ever expanding range of human membrane. gene RASSF1A and initiates the MST2-LATS1 Dukes’ staging, which measures the extent colour vision and used inCKD daylight, are most due to diabetic retinopathy. This secondary CKD progression and investigate McMorrow and Professor have with particular focus on arising from Under normal conditions, the gastrointestinal M. Rudd Journal of Proteome Research, 2010, 9 (4), pp12 13 Foundation Ireland and the Healthnovel Research interaction ofMichael academia with industry that Matthew Campbell from the NationalRyan Institute of data to various fileand formats for subsequent diseases syndromes, collectively called Codon 12 13 Codon 12 13 affected by the high glucose levels. complication of diabetes activates growthas and the Codon diabetes and hypertension. The multisignalling pathway tofunding trigger apoptosis. of tumour metastasis, we sawtool a highly strategies Status preventing wt wt&mt Status slowing mt wt Status mt&wt wt 2037–2041 for successfully secured €485,500 inthe Board. of Bioprocessing Research & Training (NIBRT) analysis. The modular architecture of the Much of the work on the project was carried ciliopathies, which have overlapping clinical of new blood award vesselstointhe theSystems eye and is disciplinarysignificant research consortium has 25 part of leaky an overall association between KRAS progression of the disease. These studies will The research team made their observations led by Conway Fellow, Professor Pauline Rudd also facilitates the manipulation of data from by UCD candidate, Sebihapartners (16features such as polycystic kidneys and be integrated with clinical and epidemiological responsible forout the death ofdoctoral photoreceptors, universities, 9 loss industry partners) Biology towards Novel Chronic Kidney However, K-Ras counteracts this using mutations MST2 protein studies a novel zebrafishand model ofofdiabetes, haveneurons developed an open access, other data management systems. the that send visual to ourwent onfrom across the consortium using systems Reference: Cevik. She andmessages herweb-based colleagues to 15 livers, retinal countries andearly thedegeneration, project is diabetic duebone to run Disease Diagnosis and Treatment (SysKid) G G TG G C G T TG G C which resembles the stages of G T TG G C pro-apoptotic action by stimulating expression in Dukes’ stages C andwell D. This is methodologies interface that facilitates extraction, querying A brain. in order Gly Val toGlydevelop Predominant cone dysfunction in a newG Gly demonstrate in C. elegans how disrupting abnormalities, hydrocephalus, as as biology Arl13b atphotoreceptor ciliary membrane for five years. consortium under the European Union FP7 The NIBRT team are now working to integrate Gly retinopathy in humans. It is an exciting Val Aspof and autocrine activation of the epidermal when the disease has advanced with local and sharing of HPLC-glycan data generated in Gly diagnostic strategies treatment options to hyperglycaemic model non-proliferative diabetic programme. development forwith the group who now hope to Until now, it was unclear if the changes to GlycoExtractor the EUROCarbDB retinopathy. Yolanda Alvarez, Jenneth Chen, Alison The UCD Conway team, including postdoctoral prevent CKD development. Email high throughput processes. further extend their and a vessels and neurons occurred independently framework toDr.provide a comprehensive highReynolds, Nore Waghorne, John O’Connor, researchers Craigresearch Slattery andestablish Dr. Natalia Syskid (www.SysKid.eu) was established to of tara.mcmorrow@ucd.ie for J. details of aBreandan PhD model of late stage diabetic disease. one other and is which type common of retinal and neuron is Kennedy. Disease Models & Mechanisms (2010) throughput analysis platform Glycosylation the most Martin, will HPLC utilise data cell culture and animalfor position currently available. further our understanding of chronic kidney Meta-analysis by UCD researchers led by of HIV nef are critical in determining the rate studies in humans have shown that non structurally diverse post-translational the storage and annotation of experimental Conway Fellow, Professor Denis Shields has of disease progression. Professor Denis progression was associated with gross modification of proteins. More than half of all data. The integration of next generation determined that there is no clear evidence Shields believes that searches for modifiers of deletions in the nef gene. gene products that haveparticular been shown to be bioinformatic tools will further the defective viral you sequences in progression rates should focus onMSc otherin larger programmes suchnow as the new We introduced 4ofnew advanced core I ammany delighted to welcome to thedevelopment However, much the research in the area to glycosylated. With specific glycans or of unified approaches for the HIV-1 nef gene or certain regions of the host and viral factors. “Systematic evaluation 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. handling large scale glycomics data initiatives glycoforms showing as cancerrole in disease proteinpotential play a significant of large quantities of data by bioinformatics studiesin rigorous, systematic academic year;than those covering principles biomarkers, there isyou an increasing needdevelopment to with applications biomarker discovery tract isConway lined with cells thatinblock theare contents results inrather both academic outputs and the in Irish biopharmaceutical progression. can be just as important refuting with in the coming months! Welcome! from the Royal Academy of Medicine UCD core technologies a scientific evaluation. This work by doctoral Glycomics needs the supporting framework cells, tissues and fluids. EUROCarbDB, athat infrastructure design NIBRT researchers Drresearch Matthew Campbell and Natalia of the gut from leaking into the intestine. In anas application of research clinical company, Sigmoid Pharma recently scooped are current in Dr the literature, develop high throughput, highly sensitive and and practical aspects toward of imaging andproduct applied Ihypotheses hope athat number of new initiatives, Ireland. fundamental infrastructural resource that HIV-infected patients can be categorised on candidate Ravindra Pushker set out to This research was partially supported by Artemenko who developed GlycoExtractor study funded by the EU 6th Framework of extensive, well-curated databases IBD patient, this barrier is broken and the development with indigenous companies.” thethat overall Innovation of and the Year award at it is in discovering unknown patterns”, he said. robust strategies detail the glycome of proteomics began in late March and will run 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 set Institute, weTimes arethis justifiably proud we are actively developing into research flexible analytical tools. Currently, field Programme. Prospective users caninto access the contents of the gut leak out surrounding the inaugural Irish All-Island instrumentsCommenting facilitate the extraction ofmodules until mid-June atheir further twodisease in on with the collaboration, them tocalibre progress to AIDS. Some ifcannot any association exists between This research wasissue, funded through Science interdisciplinary focus patients and GlycoExtractor tool of study lacks of thethe established, of research ourThe early-stage career On the occasion ofTaylor retirement, IDr wish solution providers through theConway provision described inonthis will not only areas. The research team in UCD used Innovation Awards. life-science SME, of said, data. Inflow an effort toamino alleviate Coulter “The collaboration with theplace Taylor maintain stable CD4 lymphocyte graduate, counts large andDr quantities progression and particular acid Foundation Ireland and University College genomics and cytometry taking comprehensive and centralised data http://glycobase.nibrt.ie:8080/DemoGlycoExtra a model of IBD and, by applying a new class of founded by UCD pharmacology scientists who continue to be recognised Mr Paul Rooney and Mr Cormac O’Connell of competitive and comprehensive expertise in specialist technology platforms, strengthen the community of Conway this bottleneck within high-throughput laboratory clearly demonstrates the potential do not goand on to develop AIDS even after with more differences or deletions within the nef gene.ctor/mainPage. Dublin. collections, standards information over week-long periods during the summer known as hydroxylase Ivan Coulter, has actively collaborated for the quality their to research. In inglycomic every and thankhave them sincerely for drugs offerings to and academic and inhibitors, industrialwere users. projects, the NIBRT team we uniquely placed participate the researchers forge new interdisciplinary that cansuccess be realised through focused thanare 10 years ofof infection. reporting protocols that exist within able to almost completely reverse the Conway Fellow, Professor Cormac Taylor Reference months. On a per patient basis, there was no excess of developed a web-based tool that interfaces I extend congratulations to their contribution to the Institute. Paul GlycoExtractor: was As evident in celebrate this issue,and the services and application of basic research. The development education and training of the next links but will heighten A web-based interface for high genomics and particular, proteomics. symptoms of the disease. since being Science Scientists aregranted curiousaas to whyFoundation these longLTNP patients one or more on defective nef with the Waters chromatography of a smart willsoftware depend throughput processingavailable of HPLC-Glycan data Dr Fionaindustry McGillicuddy, the first funding integral toeconomy thewith establishment andlike-minded smooth expertise are contributing to Ireland research partnership generation of research scientists. Theaward newly awareness of ourP.research and innovation term, non-Artemenko progressor (LTNP) do not sequences when compared progressors. Researchers, Dr Natalia and Dr patients package to collaborative improve and automate the to export We hope to determine from this pilot if Artemenko, Campbell, and Pauline Natalia V. “When we Matthew applied these new drugs to our IBD partners identifying opportunities recipient under the prestigious SFI-HRBoperation of the 1East laboratory while successful research outputs. Reference: in 2004. develop AIDS. This may reflect differences in While the high frequency of amino acid M. Rudd Journal of Proteome Research, 2010, 9 (4), pp launched PhD programme Bioinformatics Matthew Campbell from the National Institute of data to various filefor for subsequent successes. model, thethe gutresearch, was tricked thinking that it and realising basic of and applied research Commenting on Dr into Kennedy most likely to die as aformats result raised New research led by Conway Fellow Dr in Partnership, demand training from within as well Wellcome Trust Biomedical Cormac has been a the vital part ofUCD the UCD 2037–2041Meta-analysis to test the association of HIV-1 nef amino theResearch host, viral genetics or(NIBRT) environmental replacement at particular residues is indicative The Irish Times award recognises the stellar of Bioprocessing &Biology Training analysis. The modular architecture of the tool acid differences and deletions with disease progression. was being deprived of oxygen. This activated synergies. collaboration, initiated through and Systems recently attracted 80 glucose levels seen external inThis diabetes. Breandán Kennedy indicates that treatment said, “By establishing a robust model for early as from academic centres and factors that could potentially be exploited for of rapid evolvement, permutation testing and to Dr Darran O’Connor whoPharma wonalso theinfacilitates microscopy that recently Professor Walter Kolch innovative performance of Sigmoid led by Conway Fellow, Professor Pauline Rudd manipulation offacility data from Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields. pathways, which inwe turn prevented aelectron SFIthe research supplement, highlights the and lateprotective of diabetic blindness should look at stage diabetic retinopathy, would Professor Walter Kolch EU and 120 non-EU applicants for up to 15 industry will dictate stand-alone delivery of the of theresearch disease. showed with more replacements Journal of Virology, Apr 2010 p3644-3653 their application of and development. have developed9th antreatment open access, web-based other data management systems. St Luke’s Young Investigator award relocated toresidues the Institute Imaging Core. Director Dr Kennedy and histhat team found that new blood the death of the cells that line the potential that innovative indigenous companies protecting the studentships. neurons responsible for colour hope to better understand the progression of than expected were notcan statistically significant. these advanced modules inclusion within Director, UCD Conway InstituteProfessor The company has developed two new drug interface that facilitates querying vessels andworking the neuronal cell death inor diabetic gastrointestinal tract,” explained with academia realise.” Studies inextraction, model organisms have shownThe thatNIBRT vision in the eye and not just targeting team are now working to integrate the disease and pave the way for identifying LEDDS™ and the SmPill™, which not and sharing of technologies, HPLC-glycan data generated in Taylor. “Our pre-clinical trial data can now retinopathy The canwith arisethe independently of each infection with nef-deficient virus shows an researchers conclude current data has GlycoExtractor EUROCarbDB bloodthroughput vessels only asprocesses. isenhance currently practice. Taylor’s collaboration with that Sigmoid Pharma thethe solubility and permeability of new drug targets successful treatment”. high inform the for nextitsphase Sigmoid Pharma product other. In addition, they that cone provides noaidentified evidence that individual residues attenuated course of infection and someframework to provide comprehensive high-metrics certainly been successful by these with the drug but can deliver it to targeted locations development pipeline”. photoreceptor neurons, those involved in Nearly 2.5 million people worldwide are blind Glycosylation isinthe common and HPLCco-authored data analysis platform to fordate in twoThe publications of research was funded through Science the most gastrointestinal tract, including thethroughput three colour vision and usedranking in daylight, are journals most in the Foundation due to diabetic retinopathy. This secondary structurally diverse post-translational the storage and annotation of scientific experimental In addition thethe product that is currently in the highest Irelandtoand Health Research colon. modification More thanthe half of all data. Thebyintegration of next generation affected the high glucose levels. complication of of proteins. diabetes activates growth
Conway collaborator scoops Irish identified Times Worm research reveals cilia disease geneInnovation functionAward Unlikely oncogene accomplice
Success in EU FP7 call
GlycoExtractor advances glycan data manipulation
Zebrafish model gives insights into diabetic blindness Success in EU FP7 call
MST2 stain
results in both academic outputs and the application of research toward clinical product development with indigenous companies.”
K-Ras sequence
chemotherapeutic agent disrupts the of Bim. We have shown a novel Centre of Excellence hosts international workshop microtubule dynamics within cells association between Bim and cyclin
Irish biopharmaceutical development Prolonged mitosis leads to cell death company, Sigmoid Pharma recently scooped whereas mitosis not. at the overallnormal Innovation of the does Year award How can a cell between the inaugural Irishdistinguish Times All-Island Innovation Awards. The life-science SME, normal and prolonged mitosis to founded by pharmacology graduate, As a European Centre of Excellence, the Dr dictate cellUCD fate?
Success in EU FP7 call May Issue 101 september 2007 Issue Issue 16,2010 Spring 2012
collaborator scoops Irish Times Innovation Award Cell cycleConway control of cell death
Bioinformatic analysis of HIV progression studies
Director’s Message
Conway collaborator scoops Irish Times Innovation Award Director’s Message GlycoExtractor advances glycan data manipulation
Zebrafish model gives insights into diabetic blindness
UCD CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH
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Conway collaborator scoops Irish Times Innovation Award Molecular Trafficking Pathways in Cilia
Conway collaborator scoops Irish Times Innovation Award Conway collaborator scoops Irish Times Innovation Award Core technologies provide valuable support Irish biopharmaceutical development company, Sigmoid Pharma recently scooped Integral to the Institute infrastructure, Irish biopharmaceutical development the overall Innovation of therecently Year award at company, Sigmoid Pharma scooped UCD Conway core technologies the Irish Times All-Island the inaugural overall Innovation of the Year provide a comprehensive levelaward of at Innovation Awards. The life-science SME, the inaugural Irish Times All-Island service and expertise that is unrivalled founded by Awards. UCD pharmacology graduate, Innovation The life-science SME,Dr within Ireland. Across the four core Ivan Coulter, haspharmacology actively collaborated with founded UCD graduate, Dr areas ofbygenomics, proteomics, Conway Fellow, Professor Cormac Taylor Ivan Coulter, actively collaborated imaging andhas flow cytometry, the with Conway Fellow, Professor Cormac Taylor since being granted a Science Foundation directors and theira technical staff since being granted Science Foundation Ireland industry research partnership award adopt a problem-solving approach Ireland in 2004.industry research partnership award to the research questions posed by in 2004. The Irish Times recognises thefrom stellar scientists andaward provide support The Irish Times award recognises the stellarin innovative performance of Sigmoid Pharma experimental designoftoSigmoid publication. innovative performance Pharma in their application of research and development. their application of research development. The company has Professor developedand two newF.drug Conway Fellow, Donal The company LEDDS™ has developed two new which drug not technologies, and SmPill™, O’Shea of the Centreand for SmPill™, Synthesiswhich & not technologies, LEDDS™ only enhance the solubility and permeability of Chemical Biology recently only enhance the solubility andpublished permeability of the drug but canJournal deliver itoftothe targeted locations findings in the American the drug but can deliver it to targeted locations in the gastrointestinal including Chemical Society of tract, a study carriedtheout in the gastrointestinal tract, including the colon. in collaboration with Dr Dimitri Scholz, colon. Director of the Imaging Core. The Sigmoid Pharma-Taylor collaboration is The Sigmoid Pharma-Taylor collaboration is facilitating the development of a new facilitating the development of a new The research focused on creating the therapeutic approach for the the fluorescent treatment of of therapeutic approach for treatment next generation of smart inflammatory bowel disease (IBD) by by bringing probes that 1are notdisease only highly sensitive inflammatory bowel (IBD) bringing May 2010.qxd:Layout copy 07/05/2010 13:12 together the methodology of the the but capable of switching their fluorescent together the research research methodology of Taylor with the proprietary signal group from [off] to [on] in response to liquid/emulsion drugstimuli. specific biological delivery system, LEDDS®, developed by Sigmoid Pharma.
This would help to overcome the
Taylor Commenting the award, Professor limitation ofonnon-specific background for Dr Coulterwhen and his said, “We are delighted fluorescence often encountered team and indeed it reflects wellIton our allow using fluorescent imaging. would 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 ofto research toward clinical product researchers use continuous real-time results in both academic outputs and the development indigenous imaging rather than images captured at application of with research towardcompanies.” clinical product adevelopment specific point inindigenous time when background companies.” Commenting with on the Taylor collaboration, Dr
fluorescence has been cleared.
Coulter said, “The with the Taylor Commenting on thecollaboration Taylor collaboration, Dr laboratory clearly demonstrates the potential Coulter said, “The collaboration with the Taylor Professor O’Shea and his team describe that can beclearly realised through focused demonstrates the potential alaboratory new near-infrared, [off] to [on] application basic through research. The development that can be of realised focused fluorescent switchable nanoparticle application of basic Theits development of a smart economy will depend on like-minded construct that canresearch. switch on of a smart economy depend on like-minded collaborative partners identifying opportunities fluorescence after will cellular uptake but collaborative partners opportunities and realising basic and applied remains switched offidentifying outsideresearch of the cell and realising basic and research synergies. This collaboration, and demonstrated itsapplied usageinitiated in vitrothrough synergies. Thissupplement, collaboration, initiatedofthrough a SFI research highlights the using endocytosis as an example a apotential SFI research supplement, highlights the fundamental cellular process. that innovative indigenous companies potential that innovative indigenous companies working with academia can realise.” working with academia can realise.” ‘We were able to demonstrate in Taylor’s collaboration with Sigmoid Pharma has movie (http://www.youtube. Taylor’sformat collaboration with Sigmoid Pharma has certainly been successful by these metrics with com/watch?v=FjipbGTf8w4) certainly been successful by thesethe metrics with three co-authored publications to date in two of ability of these fluorescence responsive three co-authored publications to date in two of the highest ranking scientific journals in the nanoconstructs toscientific allow real-time the highest ranking journals in the field, Gastroenterology and Proceeding of the the continuous imaging of their uptake of field, Gastroenterology and Proceeding National Academy of hope Sciences, as well well as as the into cells. We now to expand ourthe National Academy of Sciences, as concepts inproducts vivo’, generationto of real-time proprietaryimaging innovative products generation of proprietary innovative said Professor and the the creationO’Shea. of high-skilled high-skilled jobs. jobs. and creation of Page 3
More than thanFellow, 15,000 Dr people in Ireland Ireland and More 15,000 people in and Conway Albert Smolenski millions ofSchool people worldwide worldwide are& living with with the the millions people are living from theof of Medicine symptoms IBD today. Current therapeutic therapeutic Medical Science recently published debilitating disease are options for chronic debilitating findings in this Blood of work carrieddisease out are very limited with surgery being the often being Elia the only only in collaboration with Droften Giuliano viableDroption. TheBlanco, SigmoidDirectors product, and Alfonso of the product, currently currently Proteomics and Flow Cytometry Cores in a phase II clinical study, uniquely uniquely enables enables respectively. 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 into the intestine. In an Their research study demonstrates that tract lined withleaking cells that block the contents IBD this barrier isregulator broken and the protein known asinto of the G-In an of thepatient, gut from leaking the intestine. contents of the leak out into surrounding protein signalling 18 is (RGP18) is a the target IBD patient, thisgut barrier broken and areas. The research team in into UCD Conway used in both platelet and inhibitory contents of the gutactivating leak out surrounding asignalling model ofresearch IBD and,team by applying new class pathways. areas. The in UCD aConway usedof hydroxylase inhibitors, wereof adrugs modelknown of IBDasand, by applying a new class able toknown almost completely reverse the For the first as time, they describe RGB18 drugs hydroxylase inhibitors, were as atonew substrate of protein A able almost completely reverse kinase the symptoms of the disease. (PKA) andofprotein kinase GI (PKGI). The symptoms the disease. “When applied these new drugs using to our IBD 30kDawe substrate was identified “When we newinto drugs to initial ourthat IBDit model, theapplied gut wasthese tricked thinking mass spectrometry analysis after model, the deprived gutits was tricked into thinking that it was being of oxygen. This activated evidence of existence was seen as was being deprived oxygen. This prevented activated protective pathways, in turn cross-reactivity ofofawhich phosphorylation protective pathways, in turn site-specific antibody. the death of the cellswhich that line the prevented the death of the tract,” cells that line theProfessor gastrointestinal explained gastrointestinal tract,” explained Dr Smolenski explains, “After identifying Taylor. “Our pre-clinical trial dataProfessor can now Taylor. “Our pre-clinical trial data can RGS18, wenext went on Sigmoid to define the now inform the phase Pharma product inform the next phase Sigmoid Pharma product functional outcomes development pipeline”. of RGS18 development pipeline”. phosphorylation at the molecular & In addition to theThe product that is interaction currently in cellular regulated In additionlevels. to the product that is currently in phase II clinical studies, Sigmoid Pharma of 14-3-3γ protein with RGS18 through phase II clinical studies, Sigmoid Pharma isis developing LEDDS™-enabled formulation of binding toaaeither phosphorylated serines developing LEDDS™-enabled formulation of 49hydroxylase or 218 mayinhibitor represent a switch in the the hydroxylase inhibitor the control of calcium signalling inbring platelets.” dimethyloxaloylglycine (DMOG) to to bring about dimethyloxaloylglycine (DMOG) about effective, safe safe and and targeted targeted delivery delivery of of this this effective, Reference therapeutic agent. potential potential therapeutic agent. Palma et al. Cellular Uptake Mediated Off/On Responsive Near-Infrared Fluorescent Nanoparticles. J. Am. Chem. Soc., 2011, 133 (49), pp 19618–19621
Gegenbauer et al. Regulator of G-protein signalling 18 integrates activating and inhibitory signalling in platelets. Prepublished online as Blood First Edition paper, Jan 10 2012; DOI 10.1182/blood-2011-11-390369
Under Under normal normal conditions, conditions, the the gastrointestinal gastrointestinal
Prestigious award forofConway scientist Conway collaborator scoops Irishstudies Times Innovation Award Bioinformatic analysis HIV progression Bioinformatic analysis of HIV progression studies
IrishFiona biopharmaceutical Dr McGillicuddydevelopment wins the first company, Sigmoid Pharma recently scooped award under theUCD SFI-HRB Wellcome Meta-analysis by researchers led byat the overall Innovation of the Year award Trust Biomedical Partnership. She will Meta-analysis by UCD researchers led by Conway Fellow, Professor Denis Shields has the inaugural Irish Times All-Island receive €750,000 over five years to has Conway Fellow, determined that Professor there is life-science noDenis clear Shields evidence Innovation Awards. The SME, investigate the links between obesity, determined thatdefective there is viral no clear evidenceDr that particular founded by UCD pharmacology graduate, ‘good cholesterol’, diet andsequences coronaryin that particular defective viral sequences in the HIV-1 nef has gene or certain regions ofwith the Ivan Coulter, actively collaborated artery disease. the HIV-1 nef gene or certain regions of the Conway Fellow, Professor Cormac Taylor
protein play a significant role in disease since being a Science Foundation protein play granted a significant role in disease progression.
The research project willpartnership examine how Ireland industry research award progression. obesity the function of high- on HIV-infected patients can be categorised in 2004. affects density (HDL) or ‘good the basis of the number ofbeyears itthe takes for HIV-infected patients categorised on The Irishlipoprotein Times awardcan recognises stellar cholesterol’. HDL important role them to progress toplays AIDS. Some the basis ofperformance the number ofan years itpatients takes for innovative of Sigmoid Pharma in in removing cholesterol from body, maintain stable CD4 lymphocyte counts and their application oftoresearch and the development. them to progress AIDS. Some patients which in turn reduces the of heart The company has developed two new drug do not gostable on to develop AIDSrisk even after more maintain CD4 lymphocyte counts and attack brought on by and cardiovascular technologies, LEDDS™ SmPill™, which not thannot 10go years ofdevelop infection. do on to AIDS even after more only enhance the solubility and permeability of disease. than 10 years of infection. Scientists arecan curious asittotowhy theselocations longthe drug but deliver targeted
term, progressor (LTNP) patients do not in the nongastrointestinal tract, including “First we want to determine whether Scientists are curious as to why thesethe longcolon. developobese AIDS.affects This may reflect differences in being HDL’s ability term, nonprogressor (LTNP) patients do not theeliminate host, viral cholesterol genetics or environmental to from the The Sigmoid collaboration isin develop AIDS.Pharma-Taylor This may reflect differences factors thatthe could potentiallyofbea exploited body”, McGillicuddy, from facilitating development new thefor the host,says viralDr genetics or environmental the treatment of the disease. therapeutic for theGroup treatment Nutrigenomics led of byfor factors that approach couldResearch potentially be exploited
inflammatory bowel disease (IBD) by bringing Studies in model organisms the treatment of the disease. have shown that together the research methodology of the infection withwith nef-deficient virus shows an Taylor group the proprietary Studies in model organisms have attenuated course of infection andshown some that liquid/emulsion drug delivery system, infection with nef-deficient virus shows an LEDDS®, developed by Sigmoid Pharma.
attenuated course of infection and some
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 key driver of successful
results in both academic outputs andRoche. the Conway Fellow, Professor Helen application of research toward clinical product “We then want tohave determine whether studies in humans shown that non development with that indigenous companies.” the typeinof diet the studies humans havecauses shown thatobesity non
progression was associated with gross
also playsinathe role ingene. elevating risk of progression was associated withthe gross Commenting on the Taylor collaboration, Dr deletions nef coronary artery disease. Coulter said, “The collaboration with the Taylor deletions in the nef gene. However, much the research in area to laboratory clearlyofdemonstrates thethe potential However, much of the in the area to that can realised through focused date hasbe been based onresearch observational or case For example, you can be obese from application of basic research. The development date hasarather been basedrigorous, on observational studies than systematic eating high-carbohydrate diet, or or case of a smart economy will on like-minded studies than from rigorous, systematic scientific evaluation. Thisdepend work by you canrather be obese eating adoctoral highcollaborative identifying opportunities candidate Ravindra setto out to how scientific evaluation. This work by doctoral saturated fatpartners diet.Pushker We want see and realising basic and applied research determine indifferent a substantially larger set these veryRavindra diets affect HDL candidate Pushker set outsample to synergies. This collaboration, initiated through function, and consequently thedisease risktheof set if any association exists between in asupplement, substantially larger sample adetermine SFI research highlights coronary disease. progression and particular amino disease acid if any association existsindigenous between potential that innovative companies differences deletions within the acid nef gene. progression particular amino working withorand academia can realise.”
We also know that during obesity as differences or deletions within thenonef gene.has On a percollaboration patient basis,with there was excess Taylor’s Sigmoid Pharma the fat mass (adipose tissue) expands it of LTNP patients with one or more defective nef certainly been successful by these metrics with On a per patient basis,We there was excess of becomes inflamed. plan tono investigate three co-authored publications to date in two of sequences when compared to progressors. LTNP patients with one tissue or more defective nef whether this adipose inflammation the highest ranking scientific journals in the While the high frequency of amino acid actually reduces the and ability HDL to sequences when compared to of progressors. field, Gastroenterology Proceeding of the replacement at particular residues is indicative remove cholesterol from body. Wethe While theAcademy high frequency ofthe amino acidas National of Sciences, as well of rapid evolvement, permutation testing will examine whether therapies that replacement particularnew residues isproducts indicative generation of at proprietary innovative showed fat thatinflammation residues with more replacements reduce canjobs. also improve and the creation of high-skilled of rapid evolvement, permutation testing
than expected were not statistically significant. showed that residues withinmore replacements More than 15,000 people Ireland and The conclude thatare current data thanresearchers expected were not statistically significant. millions of people worldwide living with the provides noIBD evidence that individual residues symptoms today. Current therapeutic The researchers conclude that current data are options for this chronic debilitating disease provides nowith evidence thatoften individual very limited surgery being residues the only
viable option. The Sigmoid product, currently in a phase II clinical study, uniquely enables oral delivery of a powerful drug without
tract lined withand cellsreduce that block HDLisfunction the the riskcontents of ofcoronary the gut from leaking into the In of an disease despite theintestine. presence of HIV nef are critical in determining the rate IBD patient, this barrier is broken and the of HIV nef are critical in determining the rate obesity.” of disease Professor Denis contents of progression. the gut leak out into surrounding of disease progression. Professor Denisused Shields believes thatteam searches forConway modifiers of areas. The research in UCD Shields believes that for modifiers of rates should now focus onclass otherof aprogression model of IBD and, bysearches applying a new progression rates should now focus onwere other host and viralas factors. “Systematic evaluation drugs known hydroxylase inhibitors, host viralcompletely factors. “Systematic able toand almost reverse theevaluation of large quantities of data by bioinformatics symptoms ofasthe disease. of large quantities of datainby bioinformatics can be just important refuting
can bewe just as in refuting hypotheses thatimportant are current in the literature, “When applied these new drugs to our IBDas ithypotheses is in the discovering unknown patterns”, he that aretricked current in the literature, model, gut was into thinking thatsaid. itas it isbeing in discovering unknown he said. was deprived of oxygen.patterns”, This activated This research was funded through Science protective pathways, which in turn prevented Foundation Ireland and This research was through Science the death of the cellsfunded thatUniversity line the College Dublin. Foundation Ireland and University College gastrointestinal tract,” explained Professor Taylor. Dublin.“Our pre-clinical trial data can now inform the next phase Sigmoid Pharma product development pipeline”. Reference: In addition to the product that is currently in Meta-analysis to test the association of HIV-1 nef amino phase II clinical studies, Sigmoid Pharma is Reference: acid differences and deletions with disease progression. developing a LEDDS™-enabled formulation of Meta-analysis to test the association of HIV-1 nef amino Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields. the hydroxylase inhibitor acid differences and deletions with disease progression. Journal of Virology, Apr 2010 p3644-3653 Dr Fiona McGillicuddy dimethyloxaloylglycine (DMOG) bring about Ravindra Pushker, Jean-Marc Jacquē, to Denis C. Shields. effective, andApr targeted delivery of this Journal of safe Virology, 2010 p3644-3653 potential therapeutic agent.
Gaining insight at thedevelopment molecular level Irish biopharmaceutical of the intracellular trafficking pathways company, Sigmoid Pharma recently scooped operating in cilia may light on the the overall Innovation of shed the Year award at causes of multisymptomatic cilia-related the inaugural Irish Times All-Island disorders as The polycystic kidney Innovation such Awards. life-science SME, disease, Bardet-Biedl syndrome and Dr founded by UCD pharmacology graduate, retinitis pigmentosa. Ivan Coulter, has actively collaborated with
cilary membrane resultsprotein in both and academic outputstransport and the have been of described butproduct until application research previously toward clinical now there was limited companies.” evidence that development withonly indigenous endocytosis events are also involved.
Commenting on the Taylor collaboration, Dr Success in EU FP7 call During Coulter said, “The collaboration with the Taylor endocytosis, plasma membrane Success in EU FP7 call and laboratory clearlyproteins demonstrates thethe potential associated bud off cell
that can as be internalised realised through focused surface vesicles, a process Conway Fellow, Professor Cormac Taylor disease (CKD) and improve patient treatment, Conway researchers ledresearchers by Dr. Tara led application of research. Thefunctions development New by UCD important forbasic various cellular since research 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 from by Conway Fellow, Dr Oliver Blacque in such as regulation of membrane protein disease (CKD) and improve patient treatment, Conway researchers led by Dr. Tara Ireland industry research partnership award collaborative opportunities diabetes and hypertension. The multicollaboration with colleagues in Brandeis activities andpartners uptake of extracellular successfully secured €485,500 inRyan funding as McMorrow Professor Michael have with particular focus onidentifying CKD arising from in 2004. and and realising basic andconsortium applied research University, USA has shown that endocytic molecules. disciplinary has 25 part of an overall award to the Systems diabetes and research hypertension. The multisuccessfully secured funding The Irish Times award€485,500 recognisesinthe stellaras synergies. This collaboration, initiatedpartners) through membrane transport genes facilitate protein partners (16 universities, 9 industry Biology towards Novel Chronic Kidney disciplinary part of an overall awardofto the Systems May 2010.qxd:Layout 1 copy 07/05/2010 Page 3 research consortium has 25 innovative performance Sigmoid Pharma 13:12 in a SFI research supplement, highlights the and membrane transport in C.Kidney elegans Dr Oliver Blacque said, “This is the first 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 their application of research and development. potential that innovative indigenous companies sensory cilia. demonstration anythe multicellular for five from 15 years. countriesinand project is due to run consortium under the Union FP7 Disease Diagnosis andEuropean Treatment (SysKid) The company has developed two new drug working with can connection realise.” organism of academia a functional for five years. consortium under the European Unionwhich FP7 not programme. technologies, LEDDS™ and SmPill™, These hair-like projections from eukaryotic between endocytosis and cilia. Itpostdoctoral provides The UCDcollaboration Conway team, including Taylor’s with Sigmoid Pharma has programme. only enhance the solubility and permeability of cell surfaces bear the responsibility forto acertainly springboard for future work into how The UCD been Conway team, including postdoctoral researchers Dr. Craig Slattery and Dr. Natalia Syskid (www.SysKid.eu) was established successful by these metrics with the drug but can deliver it to targeted locations motility, andwas developmental molecular systems organise the researchers Dr. Craig Dr. Natalia Syskid (www.SysKid.eu) established to Martin, willtransport utilise cellSlattery cultureand and animal further oursensation understanding chronic kidney three co-authored publications to date in two of in the gastrointestinal tract,ofincluding signalling. The functional integrity the of various structures and functions ofincilia. Martin, will utilise culture and animal further the highest rankingcell scientific journals the colon. our understanding of chronic kidney cilia depends on intracellular transport field, Gastroenterology and Proceeding of the pathways. With ciliary defects implicated more The Sigmoid Pharma-Taylor collaboration is National Academy of Sciences, as in well as the than a dozen multisymptomatic facilitating the development of a new generation of proprietary innovative diseases, products With no protein synthesis occurring in for which more than 80 genes are now therapeutic approach for the treatment of and the creation of high-skilled jobs. cilia, proteinsbowel mustdisease be trafficked the associated, our work helps to understand inflammatory (IBD) bytobringing organelle. for exocytosis how trafficking pathways More intracellular than 15,000 people in Ireland and together theRoles research methodologyinofregulating the
contribute disease aetiology.” tract is linedto with cells that block the contents of the gut from leaking into the intestine. In an Science Foundation andand thethe EU FP7 IBD patient, this barrierIreland is broken funded Dr Blacque’s contents of the gut leakresearch. out into surrounding areas. The research team in UCD Conway used Reference aKaplan model of Endocytosis IBD and, by applying a new class et al., Genes Facilitate Protein and of Membrane Transport in C. elegans Sensory Cilia, Current drugs known as hydroxylase inhibitors, were Biology able to (2012), almostdoi:10.1016/j.cub.2012.01.060 completely reverse the models to identify processes involved in early symptoms of the disease. CKD progression and investigate novel models to identify processes involved in early “When we applied these new to our strategies for preventing anddrugs slowing the IBD CKD progression and investigate novel model, thefor gutof was thinking it progression the tricked disease. These studies strategies preventing andinto slowing thethatwill was being deprived of oxygen. This activated be integrated clinical and epidemiological progression of with the disease. These studies will protective pathways, which in epidemiological turn prevented studies across theclinical consortium using systems be integrated with and 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. In addition to the product thatimage is currently Transmission electron microscopy showing in the ciliated dendritic ending of one sensory neuronisin phase II clinical studies, Sigmoid Pharma C. elegans. Inaworms with disrupted clathrin adaptorof developing LEDDS™-enabled formulation 2 complexes (endocytic mutant), the periciliary the hydroxylase inhibitor membrane (red) that exists immediately beneath dimethyloxaloylglycine (DMOG) to bring about the ciliary membrane (green) is massively expanded effective, safe deliveryaof this in compared to wildand typetargeted worms, indicating defect potential therapeutic agent. periciliary membrane recycling. 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 http://glycobase.nibrt.ie:8080/DemoGlycoExtra ctor/mainPage. ctor/mainPage. tract is linedoscillations with cells that block the contents Reference dynamics, and overshoots Reference web-based interface forhigh high GlycoExtractor: of the differing gut from leaking into the for intestine. In an AAweb-based interface GlycoExtractor: with consequences for the cell. processing HPLC-Glycan data throughput processing ofofHPLC-Glycan throughput IBD patient, this barrier is brokendata and the Natalia V. Artemenko, Matthew P. Campbell, and Pauline P. Campbell, and Pauline Natalia V. Artemenko, contents of the gutMatthew leak responses out into surrounding These can9 9(4), M.Rudd Ruddvarious Journalofofdigital Proteome Research,2010, 2010, (4),pppp M. Journal Proteome Research, areas. The research team in UCD Conway used 2037–2041 2037–2041 also trigger the creation of a biological a model of IBD and, by applying a new class of memory through hysteresis. When a drugs known as hydroxylase inhibitors, were system that depends onreverse both its able to almost completely thecurrent and past environment symptoms of the disease.is stimulated, it
GlycoExtractor advances advances glycan glycan data data manipulation manipulation GlycoExtractor
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 comprehensive and centralised data and his this bottleneck within high-throughput said, “We arestandards delighted for Dr Coulter this within high-throughput in a bottleneck phase II clinical study, uniquely enables collections, and information collections, standards and information team and indeed it reflects well on our glycomic projects, theNIBRT NIBRT team have glycomic projects, the team have oral delivery of a powerful drug without reporting protocols that exist within results in both academic outputs and the Irish 2004 biopharmaceutical development The Nobel Prize Chemistry reporting protocols that exist within and protects both proteins from rapid partnership. A key driver ofinsuccessful developed a web-based tool that interfaces developed a web-based tool that interfaces causing systemic side-effects. genomics and proteomics. application of research toward clinical product company,research Sigmoid recently scooped genomics and recognised aproteomics. landmark that destruction. scientific inPharma 2010 isdiscovery meaningful withthe theWaters Waterschromatography chromatographysoftware software with development with indigenous companies.” the overall Innovation of theindustry Year award at the generation of polyubiquitin chains Under normal conditions, the gastrointestinal interaction of academia with that package improve andautomate automate theexport export Researchers, Dr Natalia Artemenko and Dr Researchers, Dr Natalia Artemenko and Dr package totoimprove and the the target inaugural Irish Times All-Island on proteins is a signal for protein Overexpression of Bmi1 is often seenDr Commenting on the Taylor collaboration, of data to various file formats for subsequent Matthew Campbell from the National Institute Matthew Campbell from the National Institute of data to various file formats for subsequent Innovation Awards. The life-science SME, destruction. Now, evidence suggests in various human cancers and Bmi1 Coulter said, “The collaboration with of Bioprocessing Research Training (NIBRT) analysis. The modular architecture theTaylor tool of Bioprocessing &&Training (NIBRT) analysis. The modular architecture ofofthe the tool founded by UCD Research pharmacology graduate, Dr that protein ubiquitination is actually may protect cells from apoptosis byfrom laboratory clearly the potential led by Conway Fellow, Professor Pauline also the manipulation of led byCoulter, Conwayhas Fellow, Professor PaulineRudd Rudd alsofacilitates facilitates thedemonstrates manipulation ofdata data from Ivan actively collaborated with that can bemanagement realised through focusedand proaConway more versatile process and has nonsuppressing tumour suppressor have developed an open access, web-based other data systems. have developed an open access, web-based other data management systems. Fellow, Professor Cormac Taylor application basic research. The development proteolytic functions. interface that facilitates extraction, querying apoptotic of genes. interface thatgranted facilitates extraction, querying since being a Science Foundation The team working integrate The NIBRTeconomy teamare arenow nowdepend working integrate of a NIBRT smart will ontotolike-minded and sharing of data inin and sharing ofHPLC-glycan HPLC-glycan datagenerated generated Ireland industry research partnership award GlycoExtractor with EUROCarbDB GlycoExtractor withthe the EUROCarbDB collaborative partners identifying opportunities high throughput processes. The study in PLoS Computational Biology high throughput processes. This work presents a computational in 2004. May 2010.qxd:Layout 1 copy 07/05/2010 13:12 framework Page 3to provide a comprehensive highframework provide comprehensive and realisingtobasic andaapplied research highled by Professor Boris Kholodenko, Conway throughput model of the Ring1B/Bmi1 ubiquitination Glycosylation isisby the most common and HPLC data analysis platform for The Irish Times award recognises stellar Glycosylation theUCD most commonthe and throughput HPLC data analysis platform for Meta-analysis researchers led by studies in This humans have shown that non synergies. collaboration, initiated through Fellow & Deputy Director, Systems system. In partnership, it acts like an the storage and annotation experimental structurally diverse post-translational innovative performance of Sigmoid Pharmahas in Conway Fellow, Professor Denis Shields was associatedof grossthe aprogression SFI research supplement, highlights the storage and annotation ofwith experimental structurally diverse post-translational Biology Ireland shows anoflexible roleoffor the data. analog-digital converter togeneration produce integration ofofnext modification of than half their application of research and development. determined that there isMore clear evidence deletions in the nef gene. potential innovative indigenous companies data.The Thethat integration nextgeneration modification ofproteins. proteins. More than half ofall all process of ubiquitination in silencing gene bioinformatic tools will further the gene products have been shown tonew The developed two discrete signals that distinctly affect that company particular defective sequences working with academia can realise.” gene productshas have been viral shown tobe bedrugin bioinformatic tools willcan further the However, much of the research in the glycosylated. With many specific glycans or development of unified approachestrigger for area to technologies, LEDDS™ and SmPill™, which not expression. gene silencing and potentially the HIV-1 nef gene or certain regions of the glycosylated. With many specific glycans or development ofbased unified approaches foror case date hascollaboration been on Taylor’s withobservational Sigmoid has glycoforms potential asin cancer handling large glycomics data Pharma initiatives only enhance solubility and permeability different cellscale fates. protein playshowing athe significant role disease of glycoforms showing potential as cancer handlingrather large scalerigorous, glycomics data initiatives studies than systematic certainly been successful by these metrics with biomarkers, there is an increasing need to with applications in biomarker discovery the drug but can deliver it to targeted locations Polycomb proteins interact with chromatin progression. biomarkers, there is an increasing need to with applications in biomarker discovery scientific evaluation. This workto by doctoral three co-authored publications in two of develop highgenes. throughput, highly sensitive in the gastrointestinal tract, including the and to silence This process involves an Dr Lan Nguyen “The date system can This research was partially supported develop high patients throughput, highly sensitive and disease (CKD) andexplains, improve patient Conway researchers led Dr. Tara HIV-infected can by be categorised on candidate Ravindra Pushker set outtreatment, toby the highest ranking scientific journals inbythe robust strategies that detail the glycome of colon. This research was partially supported essential step where the ubiquitin ligase, generate abrupt switches where increased McMorrow and Professor Michael Ryan have robust strategies that detail the glycome of with particular focus on CKD arising from the basis of the number of years it takes for determine in a substantially larger sample set field, Gastroenterology and Proceeding of the Ring1B histone H2A. Bmi1 on Ring1B ubiquitination The Pharma-Taylor collaboration is as diabetes and hypertension. The as multisuccessfully secured €485,500 in funding themSigmoid to monoubiquitinates progress to AIDS. Some patients if any turns association exists between disease National Academy of Sciences, well as the disciplinary research consortium has 25 for Ring1B has a binding partner, Bmi1 that facilitating the development of aSystems new part of an overall award to the activity and silences gene expression, maintain stable CD4 lymphocyte counts and progression and particular amino acid generation of proprietary innovative products partners (16Itor universities, 9 industry partners) Biology towards NovelforChronic Kidney therapeutic approach the treatment facilitates the ofofRing1B example. can display multistable do not go on to self-ubiquitination develop AIDS even after more differences deletions within the nef gene. and the creation ofalso high-skilled jobs. from 15 countries and the project is due to run Disease Diagnosis and Treatment (SysKid) inflammatory bowel disease (IBD) by bringing than 10 years of infection. for five years. consortium under the European Union FP7 On a per patient basis, there was no excess of More than 15,000 people in Ireland and together the research methodology of the programme. Scientists arewith curious as to why these longLTNP patients withworldwide one or more millions of people are defective living withnef the Taylor group the proprietary The UCD Conway team, including postdoctoral term,research non- progressor (LTNP)system, patientsDrdo not sequences when compared progressors. symptoms IBD today. Current therapeutic liquid/emulsion drug delivery most likely to as aSlattery result to ofand theDr. raised New led by Conway Fellow researchers Dr.die Craig Natalia Syskid (www.SysKid.eu) was established to develop AIDS. This may reflect differences in While the frequency of amino acid options forhigh this chronic debilitating disease LEDDS®, developed by Sigmoid Pharma. glucose levels diabetes. Breandán indicates that treatment most likely to seen die asinaculture result of theanimal raised are New research led by Conway Fellow Dr Martin, will utilise cell and further ourKennedy understanding of chronic kidney the host, viral genetics or environmental replacement at particular residues is indicative very limited with surgery often being the only of diabetic Kennedy blindnessindicates should look glucose levels seen in diabetes. Breandán thatat treatment Commenting on the award, Professor Taylor Dr Kennedy and hisSigmoid team found that new factors that could potentially be exploited for of rapid evolvement, permutation testing viable option. The product, currently protecting the neurons responsible for colour results in both academic outputs and the blood Irish biopharmaceutical development Since theare start of the Professor Walter Kolch,cell Director says, of diabetic blindness should at and his said, “We delighted for2011/12 Dr look Coulter vessels and the neuronal death in diabetic the treatment of the disease. showed that residues with more replacements Dr Kennedy and his team found that new blood in a phase II clinical study, uniquely enables vision in the eye and notresponsible justrecently targeting the application competitive of research toward clinical product company, Sigmoid Pharma scooped academic year, quarterly Research “Securing research funding protecting the neurons for colour team and indeed itareflects well on our retinopathy independently of than expected were not statistically significant. oral delivery of aarise powerful drug without vessels andcan the neuronal cell death in each diabetic development with indigenous companies.” the overall Innovation of the Year award at blood vessels as is currently the practice. Frontiers session has been added in difficult economic times is extremely vision in the eye and not just targeting the Studies in model have shown that partnership. A keyorganisms driver of successful other. In systemic addition, theyindependently identified that of causing side-effects. retinopathy can each the inaugural Irish All-Island to the weekly Lecture & an challenging for arise our researchers socone itdata blood vessels asConway isinTimes currently theshows practice. infection with nef-deficient virus The researchers conclude that current scientific research 2010 is meaningful Commenting on the Taylor collaboration, photoreceptor neurons, those involved in Dr Nearly 2.5 million people worldwide areSME, blind other. In addition, they identified that cone Innovation Awards. The life-science Seminar Series (CLASS). Up to four is vitally important that we celebrate provides no evidence that individual residues attenuated course of infection and some Under normal conditions, the gastrointestinal interaction of academia withThis industry that Coulter said, and “The collaboration with colour vision and used inthose daylight, arethe most due to diabetic retinopathy. secondary Glycomics needs the supporting framework cells, tissues fluids. photoreceptor neurons, involved inTaylor Nearly 2.5byFellows million people worldwide blind founded UCD pharmacology graduate, Dr Conway are invited to are make a all grant award successes and keep laboratory demonstrates the are potential affected by clearly theand high glucose levels. complication of diabetes activates the growth of extensive, well-curated databases and colour vision used in daylight, most due toCoulter, diabetic retinopathy. This Ivan has actively collaborated with summary presentation on asecondary research our research community informed of Commercial packages that support HPLC flexible analytical tools. Currently, this that can be realised through focused of new leaky blood vessels inCormac the eyerecently andfield is proposal for which they have ongoing work.” Conway Fellow, Professor Taylor affected by the high glucose levels. complication of diabetes activates the growth instruments cannot facilitate extraction of The research team made theirthe observations of study lacks the established, application of basic research. The development responsible for the death of photoreceptors, secured a funding award and all large quantities of data. In an effort to alleviate since being granted a Science Foundation of new leaky blood vessels in the eye and is using a novel zebrafish model of on diabetes, comprehensive and centralised data to our of a smart economy will depend like-minded the neurons that send visual messages The research team made their observations this bottleneck within high-throughput awardees in the previous quarter are Ireland industry research partnership award At the inaugural session in September responsible for the death of photoreceptors, which resembles the early stages of diabetic collections, standards and information collaborative partners identifying opportunities brain. using a novel zebrafish model of diabetes, glycomic projects, the NIBRT team have acknowledged. in 2004. 2011, Professors Ulla Knaus and the neurons that send to our reporting protocols thatvisual existmessages within retinopathy in humans. It is an exciting and realising basicthe andearly applied developed a web-based toolstages thatresearch interfaces which resembles of hope diabetic genomics and proteomics. development forcollaboration, the group who now to Until now, Times it was unclearrecognises if the changes to brain. The Irish award the stellar synergies. This initiated through with the Waters chromatography software retinopathy intheir humans. It is and an exciting further extend research establish a vessels and neurons occurred independently of innovative performance of Sigmoidand Pharma in package to improve and automate the export Researchers, Dr Natalia Artemenko Dr a SFI research supplement, highlights the development for thediabetic group disease. who now hope to Until now,and it was unclear if the changes to is model of late stage one other which typethe of retinal neuron their application of research and development. Matthew Campbell from National Institute of data to various file formats for subsequent potential that innovative indigenous companies Meta-analysis by UCD researchers led by of studies in humans shown non a further extend theirhave research andthat establish vessels and neurons occurred independently The company hasResearch developed two new drughas of Bioprocessing & Training (NIBRT) analysis. The was modular architecture of the tool working can realise.” Conway Fellow, Professor Shields progression associated with gross model ofwith lateacademia stage diabetic disease. one other and LEDDS™ which type ofDenis retinal neuron isnot also facilitates the manipulation of data from led by Conway Fellow, Professor Pauline Rudd technologies, and SmPill™, which determined that there is no clear evidence deletions in the nef gene. Taylor’s collaboration with Sigmoid Pharma has have developed ansolubility open access, web-based of other data management systems. only enhance the andsequences permeability that particular defective viral in interface that can facilitates extraction, querying certainly successful by these metrics However,been much of the research in the area with to the drug deliver it to targeted locations the sharing HIV-1but nef gene or certain regions of the The NIBRT team are now working to integrate and of HPLC-glycan generated three co-authored publications to date in date has been with based onEUROCarbDB observational or two caseof in the gastrointestinal tract, data including the in GlycoExtractor the
Conwayrole collaborator scoops Irish Times Innovation Award Ubiquitination in gene silencing
Bioinformatic analysis of HIV progression studies
Success in EU FP7 call
‘remembers’ the stimulus and will only
“When appliedlevel theseofnew drugs towhen our IBD requirewe a lower stimulus model, the gut was tricked into thinking that it subsequently exposed”. of HIV nefdeprived are critical in determining the rate was being of oxygen. This activated of diseasepathways, progression. Professor Denis protective which in turn prevented Nobel laureate, Professor Shields believes that searches for modifiers of the death of the cells that lineAaron the Ciechanover collaborated the research progression rates should nowonfocus on other gastrointestinal tract,” explained Professor that funded by Science host was and viral factors. “Systematic Taylor. “Our pre-clinical trial dataFoundation canevaluation now Ireland and thephase National of large quantities of data byInstitutes bioinformatics inform the next Sigmoid Pharma of product can be just as important in refuting Health. development pipeline”. NIBRT researchers Dr Matthew Campbell and Dr Natalia hypotheses thatDrare current in theand literature, NIBRT researchers Matthew Campbell Dr early Nataliaas Artemenko GlycoExtractor models towho identify processes involved in In todeveloped the product that is currently Reference it addition is progression in discovering unknown patterns”, heinsaid. Artemenko who developed GlycoExtractor CKD and investigate novel Switches, ResponsesSigmoid and Oscillations in theis phase II Excitable clinical studies, Pharma strategies for preventing and slowing the Ring1B/Bmi1 Ubiquitination System. Nguyen et al. PLos This research was funded through Science developing a LEDDS™-enabled formulation of progression of the disease. These studies will Computational Biology Dec doi/10.1371/journal. Foundation Ireland and2011 University College the hydroxylase inhibitor be integrated with clinical and epidemiological pcbi.1002317 Dublin.across the consortium dimethyloxaloylglycine (DMOG)using to bring about studies systems effective, safe and targeted delivery of this new biology methodologies in order to develop potential therapeutic agent. diagnostic strategies and treatment options to
Zebrafish Zebrafish model model gives gives insights insights into into diabetic diabetic blindness blindness prevent CKD development. Email Award Innovation Commenting on the research, Dr Kennedy tara.mcmorrow@ucd.ie for details of a PhD ResearchConway Frontierscollaborator in CLASS scoops Irish Times Reference:
Commenting the research, DrHIV-1 Kennedy said, “Bycurrently establishing a robust of model for early position Meta-analysis to on test available. the association nef amino
and late stage diabetic retinopathy, we would said, “By establishing a robust model for early acid differences and deletions with disease progression. Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields. tract lined with cellsPIthat block the contents hope toEricsson better understand the progression of and is late stage diabetic retinopathy, we would Johan (SFI awards) and Dr Journal of Virology, Apr 2010 p3644-3653 of the gut from leaking into thefor intestine. In an the disease and paveResearch the way identifying John Baugh (HRB Training hope to better understand the progression of IBD this barrier is broken the Fellowships) presented. Professors new drug targets for itsthe successful treatment”. thepatient, disease and pave way forand identifying contents of the gut leak outHiggins into surrounding Cormac and (SFI PI newresearch drugTaylor targets for Des its successful treatment”. The was funded through Science areas. Theand research team Blacque in UCD Conway awards) Dr Oliver (SFI PIused EUROCarbDB, a research infrastructure design Ireland and the Healthaspoke Research aFoundation model of IBD and,funded by applying new class Career Advancement award) in of The research was through Science study funded by hydroxylase the EU 6th Framework Board. drugs known as inhibitors, were January 2012. Foundation Ireland and the Health Programme. Prospective users can Research access the able to almost completely reverse the Board. GlycoExtractor tool on symptoms of the disease. http://glycobase.nibrt.ie:8080/DemoGlycoExtra
GlycoExtractor advances glycan data manipulation
Reference:
ctor/mainPage. “When we applied these new drugs to our IBD Bioinformatic analysis of HIV progression studies model, the gut was tricked into thinking that it Predominant cone photoreceptor dysfunction in a
Reference: Reference hyperglycaemic model of non-proliferative diabetic GlycoExtractor: A web-based interface for high Predominant cone photoreceptor dysfunction in a retinopathy. Yolanda Alvarez, Jenneth Chen, Alison was beingprocessing deprived oxygen. This throughput ofofHPLC-Glycan data activated hyperglycaemic model ofwhich non-proliferative diabetic Reynolds, Nore Waghorne, JohnP. J.Campbell, Breandan Natalia V. Artemenko, Matthew and Pauline protective pathways, inO’Connor, turn prevented retinopathy. Alvarez, Jenneth Alison Kennedy. Disease Models & Mechanisms (2010) M. Rudd Journal of Proteome 2010, 9 (4), pp the death ofYolanda the cells that line theChen, of HIV nef are critical in Research, determining the rate 2037–2041 Reynolds, Nore Waghorne, John J. O’Connor, Breandan
gastrointestinal tract,” explained Professor of disease progression. Professor Denis Kennedy. Disease Models & Mechanisms (2010) Taylor. pre-clinical trial dataforcan now of Shields“Our believes that searches modifiers inform the next phase Sigmoid Pharma progression rates should now focus onproduct other development host and viralpipeline”. factors. “Systematic evaluation