Conway Focus Issue 17 Summer 2012

Irish primary biopharmaceutical The cilium is development a highly company, Sigmoid Pharma specialised sensory and recently signal scooped the overall Innovation of the Year award at transduction hub that plays a central the inaugural Irish Times All-Island role in diverse cellular processesSME, such Innovation Awards.

The life-science as differentiation, polarity and cell Dr founded

by UCD pharmacology graduate, As a Coulter, European Centre of07/05/2010 Excellence, the Ivan actively collaborated with cycle progression.

Primary cilia are May 2010.qxd:Layout 1has copy 13:12 Conway Fellow, Professor Taylor absent in several cancerCormac cell types Department of Rheumatology in St Vincent’s since being granted a Science Foundation such as breast andwas pancreatic University Hospital chosen to cancers. host an

results in both academic outputs and the American Journal of Physiology-Renal application of research toward clinical product Physiology, the team demonstrated that development with indigenous companies.” exposure to carcinogens (ochratoxin A Commenting on the Taylor collaboration, and potassium bromate) significantlyDr Coulter said, collaboration with the Taylor reduced the“The percentage of ciliated renal laboratory clearlyprogramme demonstrates the potential cells.

Transcriptomic analysis identified The Participate focused on Page 3 that can important be realised through focused several signalling pathways advanced treatment regimens for RA in the applicationinofmediating basic research. The development involved effects. clinic, including practicalthese aspects of biologic

tract is lined with cells that block the contents Reference ofRadford, the gut from leaking into theloss intestine.

In an R et al. Carcinogens induce of the primary IBD patient, this barrier is broken and thecells cilium in human renal proximal tubular epithelial contents of the gut leak outcell into surrounding independently of effects on the cycle.

Am J Physiol Renal Physiol (2012) 302(8):F905-16. areas.

The research team in UCD Conway used a model of IBD and, by applying a new class of Addressing internationalinhibitors, guests, Ms Mary drugs known the as hydroxylase were able to Director almost completely Duff, of Nursingreverse and Ms.the Kay symptoms the disease.

Connolly, of Assistant Director of Nursing for the

Centre of Excellence hosts international workshop

Ireland industry research partnership award international two-day workshop on March in 2004.

Research from theSponsored UCD Renal 26thIrish & 27th 2010. byDisease Roche The Times award recognises the stellar Research Group (www.ucd.ie/renal) innovative performance ofworkshop Sigmoid Pharma Pharma, the Participate gaveled in by Conway Fellow, Dr Tara McMorrow their application of research and development. twenty rheumatologists from centres in and collaborators, Professor The company has developed twoMichael new drug Europe andDrAustralia the to not Ryan and Oliver Blacque, has which technologies, LEDDS™ andopportunity SmPill™, only enhance thethat solubility and permeability of witness the care of patients with rheumatoid demonstrated known renal the drug but it tostructure targeted locations carcinogens disrupt cilia and arthritis (RA)can at deliver St Vincent’s. in the gastrointestinal tract, including function in tubular epithelial cells.the colon.

In study, recently published in the is Thea Sigmoid Pharma-Taylor collaboration

facilitating the development of a new therapeutic approach for the treatment of inflammatory bowel disease (IBD) by bringing together the research methodology of the Taylor group with the proprietary liquid/emulsion drug delivery system, LEDDS®, developed Sigmoid Pharma.central An image of the frogbypeptide structure Irish biopharmaceutical development

of a smart economy will depend on like-minded therapy carried out inidentifying the accredited infusion collaborative partners opportunities

The work carried out care in conjunction and realising basic and applied research suite that was provides optimal for RA with scientists in Austria, Switzerland and synergies.

This collaboration, initiated through patients. In addition to lectures from Conway The as part of the EU the FP6 aFellows, SFINetherlands research supplement, highlights Professors Oliver FitzGerald and project, potential CarcinoGENOMICS. that innovative indigenous companies

Douglas Veale, delegates heard from clinical nurse specialists about education, Dr McMorrow plans topatient expand this Taylor’s collaboration with Sigmoid Pharma has screening and monitoring of mechanisms biological research by characterising of certainly been successful by these metrics with therapies. primary cilium loss during carcinogenesis working with academia can realise.”

three co-authored publications to date in two of and exploreranking the application of thisin the the highest scientific journals research as a novel screening method for field, Gastroenterology and Proceeding of the potential chemical carcinogenicity.

National Academy of Sciences, as well as the generation of proprietary innovative products and the creation of high-skilled jobs.

“When weJoint applied new drugs ourthat IBD Bone & Unitthese expressed their to hope model, the gut was tricked into thinking that the experience of the multidisciplinary teamit was being deprived of oxygen. This activated from St Vincent’s would provide a template for protective pathways, which in turn prevented delegates reproduce the death ofto the cells thatsimilar line thecare and facilities for thetract,” management RA patients in gastrointestinal explainedofProfessor Taylor.

“Our pre-clinical trial data can now their respective countries. inform the next phase Sigmoid Pharma product development pipeline”.

Hair-like structures known as cilia (red), located on the Insurface addition to the productcells, thatmay is currently inor of kidney epithelial be damaged phase clinical studies, lost byIIcarcinogen exposure.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

Conway collaborator Irish Times Innovation Award New insight to CO2 sensingscoops and signalling There is aSigmoid Jekyll and Hyde quality to to the work ofona the UCD Conway research team company, Pharma recently scooped Commenting award, Professor Taylor impact of hypercapnia or elevated levels was selected as the front cover image for the the overall Innovation award at said, “We are delighted of forthe Dr Year Coulter and his of CO the body.

In scientific inflammatory 2 inindeed April 2010 edition of the journal, team and it reflects well on our the inaugural Irish Times All-Island conditions asThe chronic obstructive partnership.

Asuch key driver ofActa successful BiochimicaAwards. et Biophysica (BBA);SME, Innovation life-science scientific research in 2010 or is meaningful lung disorder cystic fibrosis, founded by UCD(COPD) pharmacology graduate, Dr Proteins & Proteomics. interaction of has academia with industry Ivan Coulter, actively collaborated with hypercapnia is associated with athat worse PeptidesFellow, in for the skin of many species of frog Conway Professor Cormac Taylor prognosis patients as it results in have anti-bacterial and anti-fungal properties since being granted a Science Foundation them being susceptible to infection.

More than 15,000 people in Ireland and millions of people worldwide are living with the symptoms IBD today. Current therapeutic options this chronic debilitating disease are varietyinfor ofboth solutions in order to understand results academic outputs and the the very limited with surgery often being the only responses, itresearch is for becoming increasing structural basis thetoward difference in biological application of clinical product viable option.toThe Sigmoidthe product, important decipher exact currently development with indigenous companies.” activity. in a phase II clinical study, uniquely enables molecular pathway by which it operates. oral delivery of a powerful drug without Commenting onXT-7 the Taylor collaboration, Dr the This particular peptide, isolated from causing systemic side-effects.

Coulter said, “The collaboration with thebyTaylor skin of Silurana tropicalis, shows potential for New findings from researchers led drug development as it has impressive activity Conway Fellow, Professor Cormac Taylor that can be realised through focused against the of bacteria and Candida provide thegrowth beginnings of a molecular application of basic research. The development understanding of how elevated can albicans.

However, this potential asCO an 2antia smart3economy will depend on like-minded May 2010.qxd:Layout copy 07/05/2010 13:12 of Page as well as the1ability to lyse or rupture award Ireland industry research partnership affect immune/inflammatory signalling. infective agent is restricted by itsopportunities haemolytic collaborative partners identifying mammalian This innate immunity in 2004.

In contrast,cells. hypercapnia and associated activity. and realising basic and applied research protects from award These properties of The Irish itcan Times recognises stellar acidosis beattack. associated withthe improved Senior author, Dr Eoin Cummins synergies.

This collaboration, initiatedexplains, through frog skin peptides are exciting fromPharma the ASFI change to the structure the ofofthe innovative performance of Sigmoid in patient outcome in instances where a“We research supplement, highlights identified aamino novelacid modulation prospect of being developed intodevelopment. their application of research and XT-7 peptide can createindigenous an analogue that potential that innovative companies clinicians reduce mechanical damage to a key innate immunity/inflammatory Meta-analysis by UCD researchers byantistudies in humans have shown that non therapeutically valuable anti-infective and The company has developed newled drug retains anti-infective without the working with was academia can realise.” the lungs of patients with two acute respiratory Conway Fellow, Professor Shields progression withbut gross pathway (NFκassociated B). Aproperties key transcription cancer agents. technologies, LEDDS™ and Denis SmPill™, whichhas not complicating haemolytic activity. The single distress syndrome using therapeutic determined that there is noaclear evidence deletions in the nef gene. factor in this pathway, is processed Taylor’s collaboration with RelB Sigmoid Pharma has only enhance the solubility and permeability of that particular defective viral sequences amino acid substitution (glycine replaced by hypoventilation strategy.

Conway Fellow, Dr Chandralal Hewagelocations andinhis certainly been successful by these metrics and localised differentially under However, much of the research in the area with to the drug but can deliver it to targeted the HIV-1 nef gene or certain regions of the lysine) improves the therapeutic potential of of team carried out molecular modelling of the three co-authored publications to date in two date has been based on observational or case in the gastrointestinal tract, including the conditions of elevated CO that may 2 protein play a significant role in disease XT-7 peptide and itsrecognition analogue [G4K]XT-7 thishighest naturally occurring peptide.

With CO2 gaining as an in a studies rather than scientific rigorous, systematic the ranking journals in the colon. progression. influence NFκB dependent signalling.” scientific evaluation. This by doctoral field, Gastroenterology andwork Proceeding of the intracellular signalling molecule that can The Sigmoid Pharma-Taylor is HIV-infected can be collaboration categorised on candidate RavindraofPushker setasout to as the National Academy Sciences, well affect both patients inflammatory and immune the basis ofthe thedevelopment number of years it takes for determine in substantially larger sample set facilitating of a new generation of aproprietary innovative products them to progress to AIDS. Some patients if any association exists between disease therapeutic approach for the treatment of and the creation of high-skilled jobs. maintain stable CD4 disease lymphocyte and progression and particular amino acid inflammatory bowel (IBD)counts by bringing do not gothe onresearch to develop AIDS even of after differences or deletions the nef More than 15,000 peoplewithin in Ireland andgene. together methodology themore than 10 years of infection. millions of people worldwide are living with the Taylor group with the proprietary On a per patient basis, there was no excess of symptoms IBD with today.

Current therapeutic liquid/emulsion drug delivery system, Scientists are curious as why these LTNP patients one or more defective Conway scientists at to every levellongwere Research Fellow, Dr David Croucher results in both academic outputs and the nef Irish biopharmaceutical development options forfunding this chronic debilitating disease are term, non-developed progressor patients do not sequences when compared to clinical progressors.

LEDDS®, by(LTNP) Sigmoid Pharma. application of research toward product company, Sigmoid Pharma recently scooped recognised for their research through received under the Science A new fortnightly forum for Conway graduate decided by the members but itfirst is envisaged develop AIDS. This mayofreflect differences While the high frequency of amino acid very limited with surgery often being the only development with indigenous companies.” the overall Innovation the Year award atin personal and funding awards in the Foundation Ireland starting investigator and postdoctoral researchers will be launched that it will include a mix of technology Commenting theTimes award, Professor Taylor viralon genetics or environmental replacement particular indicative the host, inaugural Irish All-Island viable option.atThe Sigmoidresidues product,iscurrently last quarter. research grant (SIRG) programme with Commenting on the Taylor collaboration, Dr in May 2010.

Thispotentially initiative will give earlyoverviews, and formal research said, “We are delighted Dr Coulter and for his factors that could be exploited of evolvement, permutation testing Innovation Awards.

Thefor life-science SME, in arapid phase IIinformal clinical study, uniquely enables Coulter said, “The collaboration with the Taylor co-funding from the International Marie stage researchers the opportunity to seminars, PhD viva rehearsals and career team and indeed it reflects well on ourtalk about the treatment of the disease. showed that residues with more replacements founded by UCD pharmacology graduate, Dr oral delivery of a powerful drug without laboratory clearly demonstrates thewill potential than expected were not statistically significant.

Conway Fellow, Dr John O’Connor Curie COFUND scheme.

David partnership.

Aissues keyactively driver ofcollaborated successful Ivan Coulter, has science and that concern them inwith an development talks from within and beyond causing side-effects.

Studies in model organisms have shown that that can systemic be realised through focused Conway Fellow, Professor Cormac Taylor scientific research in 2010 is meaningful was selected by the Royal Academy of look at the fundamental behaviour of informal environment with refreshments academia.

Forum committee members, PhD infection with nef-deficient virus shows an The researchers conclude thatThe current data application of basic research. development since being Science Foundation Under normal conditions, the gastrointestinal interaction ofgranted academia with industry that provided!

Content forainfection the forum be student Mr Thomas Medicine in Ireland to deliver the 2012 signalling in breast cancer provides nopathways evidenceSchwarzl that individual residues attenuated course of andwill some Under normal conditions, the gastrointestinal laboratory clearly demonstrates the potential

tract is lined with cells that block the contents The used murine of thegroup gut from leaking intoand the human intestine. In an models of lung injury to show thatthe RelB is IBD patient, this barrier is broken and cleaved of and to the of cells in contents thesent gut leak outnucleus into surrounding response elevated areas.

The to research teamarterial in UCD CO Conway used 2. a model of IBD and, by applying a new class of drugs known as hydroxylase Science Foundation Irelandinhibitors, funded were able almost completely this to research including areverse short the term symptoms of the disease. travel fellowship to Dr Cummins to

Northwestern University, “When we applied these new USA. drugs to our IBD

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

was being deprived of oxygen. This activated protective Reference pathways, which in turn prevented the deathetofal.the cells that line the Oliver, Cleavagethe Andrate of HIVKMnef areHypercapnia critical inInduces determining gastrointestinal tract,” explained Professor Nuclear Localisation Of RelLB Giving Insight Into CO2 of disease progression.

Professor Denis Sensing And Signalling.

Journal of Biological Chemistry Taylor.

“Our pre-clinical trial dataforcan now of Shields believes that searches modifiers (2012) doi:10.1074/jbc.M112.347971 inform the next phase Sigmoid Pharma progression rates should now focus onproduct other development host and viralpipeline”. factors. “Systematic evaluation of quantities April 2010 edition of Biochimica et Biophysica ofCover large of data by bioinformatics Incan addition product that is currently in Acta (BBA); Proteins & Proteomics. be justto asthe important in refuting

phase II clinical Sigmoid is as hypotheses thatstudies, are current in thePharma literature, developing a LEDDS™-enabled formulation of it is in discovering unknown patterns”, he said. the hydroxylase inhibitor This research was funded through Science dimethyloxaloylglycine (DMOG) to bring about Foundation Ireland and University College effective, safe and targeted delivery of this Dublin. potential therapeutic agent.

collaborator scoops Irish Times Recognising excellence in research Launch ofConway Conway postdoctoral & graduate forumInnovation Award

Ireland industry research partnership award

Conway Review Lecture and receive the in 2004.

Academy silver medal in recognition of The Irish Times award recognises the stellar his work on the effectofpro-inflammatory innovative performance Sigmoid Pharma in agents have onofsynaptic their application researchsignalling and development.

The company has developed new to drug before and during hypoxictwo insults technologies, LEDDS™ and SmPill™, which not neurons.

of a smart economy will depend on like-minded using systems biology approaches. collaborative partners identifying opportunities and realising basic and applied research synergies. collaboration, initiated Research This Fellow, Dr Silke Ryan wonthrough the a SFI research supplement, highlights the 2012 James B. Skatrud new investigator potential that innovative indigenous companies award at theacademia annual conference working with can realise.” of the

tract lined with that blockhypoxia the contents andisthe role of cells intermittent ofinthe from leaking into the intestine. In an thegut development of )cardiovascular (thomas.scharzl@ucd.ie and postdoctoral Reference: IBD patient, this barrier is broken and the complications by selectively Meta-analysis to Dr testin theOSAS association of HIV-1 nef amino researchers, David Gomez contents of theand gut leak out surrounding acid differences deletions withinto disease progression. activating inflammatory pathways. (david.gomez@ucd.ie) and Dr Craig Slattery areas.

The research team in UCD Conway used Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields. (craig.slattery@ucd.ie ) p3644-3653 invite suggestions Apr by 2010 aJournal modelofofVirology, IBD and, applying a new classfor of drugs knownschedule. as Fellow, hydroxylase inhibitors, were the forum Postdoctoral Dr Maria Prencipe able almost completely reverseInvestigators the wontothe 2012 DAMC Young symptoms of the disease.

Research Symposium laboratory-based “When we applied these new Maria’s drugs toresearch our IBD oral presentation award. model, theon gutfinding was tricked into thinking that it focuses potential therapeutic was being deprived of oxygen. This activated targets for treatment-resistant prostate protective pathways, which in turn prevented cancer she presented the deathcells of theand cells that line the work on a candidate biomarker, serum response gastrointestinal tract,” explained Professor Taylor. pre-clinical trial data can now factor“Our (SRF).

Bioinformatic analysis of HIV progression studies

only enhance the solubility and permeability of the drug but can deliver it to targeted locations Meta-analysis

by UCDtract, researchers in the gastrointestinal includingled theby colon.

Conway Fellow, Professor Denis Shields has

determined that there is no clear evidence

The Sigmoid Pharma-Taylor collaboration is that particular defective viral in facilitating the development of sequences a new the HIV-1 nef gene orfor certain regions of therapeutic approach the treatment of the protein play abowel significant role in disease inflammatory disease (IBD) by bringing progression. together the research methodology of the Taylor group with the proprietary HIV-infected patients can be categorised on liquid/emulsion drug delivery system, the basis of the number of years Pharma. it takes for LEDDS®, developed

by Sigmoid

Investing in Your to Future them to progress AIDS. Some patients

Commenting onCD4 the award, Professor Taylor maintain stable lymphocyte counts and said, “We are delighted for Dr Coulter and his do not go on to develop AIDS even after more team and indeed it reflects well on our than 10 yearsA of infection. partnership. key driver of successful scientific in 2010 meaningful Scientistsresearch are curious as toiswhy these longinteraction of academia with industry that

term, non- progressor (LTNP) patients do not develop AIDS. This may reflect differences in

American Thoracic Society. Silke works Taylor’s collaboration with Sigmoid Pharma has on obstructive sleep apnoea syndrome certainly been successful by these metrics with

three co-authored date in two of studies in humanspublications have showntothat non the highest ranking scientific with journals in the progression was associated gross field, Gastroenterology and Proceeding of the deletions in the nef gene.

National Academy of Sciences, as well as the generation of proprietary innovative products However, much of the research in the area to and of high-skilled jobs. or case datethe hascreation been based on observational

inform the next phase Sigmoid Pharma product development pipeline”.

of HIV nef are critical in determining the rate

Inofaddition the product Professor that is currently disease to progression.

Denis in phase II clinical Sigmoid is of Shields believesstudies, that searches forPharma modifiers developing a LEDDS™-enabled of progression rates should now formulation focus on other the hydroxylase inhibitor Quinn host and viral factors. “Systematic Elaine evaluation dimethyloxaloylglycine (DMOG) to bring about Communications Education Officer of large quantities of data by&bioinformatics effective, safe and targeted delivery of this studies rather than rigorous, systematic UCD Conway Institute Biomolecular &inBiomedical More than 15,000 people in Ireland and can beofjust as important refuting Research potential therapeutic agent. scientificofevaluation.

This work doctoral millions people worldwide areby living with the University College Dublin hypotheses that are current in the literature, as candidate Ravindra Pushker out to symptoms IBD today.

Currentset therapeutic it is in discovering unknown patterns”, he said.4 Belfield, Dublin determine a substantially larger sample options for in this chronic debilitating diseaseset are Ireland very with surgery often being the only if anylimited association exists between disease This research was funded through Science viable option.and Theparticular Sigmoid product, currently progression amino acid Foundation Ireland and E: University College elaine.quinn@ucd.ie in a phase IIor clinical study, uniquely enables differences deletions within the nef gene.

Dublin.

T: (+353-1) 716 6706 oral delivery of a powerful drug without F: (+353-1) 716 6701 On a persystemic patient basis, there was no excess of causing side-effects.

LTNP patients with one or more defective nef sequences when compared to progressors.

While the high frequency of amino acid

W: www.ucd.ie/conway

Under normal conditions, the gastrointestinal

Reference:

Success in EU FP7 call May Issue 101 september 2007 Issue Issue 17,2010 Summer 2012

Conway collaborator IrishinTimes Award Carcinogen exposure causesscoops cilia loss renalInnovation cells

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

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

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

GlycoExtractor advances glycan data manipulation cells, tissues and fluids.

EUROCarbDB, a research infrastructure design Glycomics needs the supporting framework of extensive, well-curated databases and study funded by the EU 6th Framework Commercial packages that support HPLC Programme. Prospective users can access the flexible analytical tools. Currently, this field instruments cannot facilitate the extraction of GlycoExtractor tool on of study lacks the established, large quantities of data. In an effort to alleviate comprehensive and centralised data http://glycobase.nibrt.ie:8080/DemoGlycoExtra this bottleneck within high-throughput collections, standards and information ctor/mainPage. glycomic projects, the NIBRT team have reporting protocols that exist within Reference developed a web-based tool that interfaces GlycoExtractor: A web-based interface for high genomics and proteomics. with the Waters chromatography software tract is lined cells thatdata block thediabetes, contents results in both academic outputs and the Irish biopharmaceutical development throughput processing ofwith HPLC-Glycan Research by Conway Fellow, Dr Oliver the function of worm Arl13b causes the complex traits including obesity, endoplasmic reticulum are modified as they Previous studies on the secretory process Secretion is a fundamental process package to application improve and automate the and export Researchers, Dr Natalia has Artemenko and Drrecently Natalia V. of Artemenko, Matthew P. and Campbell, Pauline In an thealong gut from leaking into theand intestine. of research toward clinical product company, Sigmoid Pharma scooped Blacque revealed new information ciliary membrane toout bulge become mental retardation even cancer. pass the secretory pathway through have been carried in more simplistic essential to almost every cell type in of Proteome Research, 2010, 9 and (4), pp Matthew Campbell from the Nationalof Institute file formats for subsequent IBD patient, this barrier is broken the development with indigenous companies.” M. Rudd Journal the overall Innovation the Year awardofatdata to various aboutbody; a gene implicatedhormones in Joubert misshapen as well the ability 2037–2041 of the Golgiofapparatus toout theinto cellsurrounding surface. organisms such as as theaffecting fruit (Drosophila) the delivering analysis.(CKD) The modular architecture of thefly tool of Bioprocessing Training contents the gut leak theResearch inaugural Times(NIBRT) All-Island into Dridentify Oliver Blacque hopes that these findings models to processes involved in early disease andproteins improve patient treatment, Conway researchers led and by&Irish Dr. Tara Commenting on the Taylor collaboration, Dr syndrome related cerebellar disorders other to properly distribute within or with a more narrow focus such as on a blood stream, digestive enzymes led by Conwaythe Fellow, Professor Pauline Rudd also facilitates the manipulation of data from areas.

Theand research team innovel UCD Conway used Innovation Awards. The life-science SME, will ultimately lead to a greater CKD progression investigate McMorrow and(JSRDs), Professor Michael Ryan have with particular focus on CKD arising from Coulter said, “The collaboration with the Taylor characterised by blindness, bone the ciliary membrane. other data management systems. have developedinto an open access, web-based secretory pathway hasJSRDs, the capacity specific group of genes. Now, using highstrategies aThe model of IBD and, by applying a new class to of founded UCDand pharmacology graduate, Dr thebygut, signalling molecules understanding of for preventingnot andonly slowing the but also laboratory clearlyThe demonstrates the potential diabetes and hypertension. multisuccessfully €485,500 inquerying funding as abnormalities, kidneys, interface that secured facilitates extraction, drugs known as hydroxylase inhibitors, were Ivan Coulter, hascystic actively collaborated with cope with a wide variety of cargo molecules, content screening, we have been able toprogression between cells.

The NIBRT team are now working to integrate They also found that a fully functional of closely related ciliopathies such as that can be realised through focused of the disease.

These studies will disciplinary research consortium has 25 part of an overall award to the Systems and sharing of developmental HPLC-glycan data generated in of Taylor able to almost completely reverseregulatory the Conway Fellow, Professor delay andCormac loss muscle and aswith such utilises extensive target 22,000 human genes and track the GlycoExtractor with the of EUROCarbDB basic research. development be integrated clinical and epidemiological Arl13b protein needed forThe the normal Meckel Gruber Bardet-Biedl syndrome,ma(16application universities, 9isindustry partners) high throughput processes.

Biology towards Novel Chronic Kidney symptoms of theand disease. since being granted a Science Foundation tone and control.

The findings of thispartners framework of to provide a comprehensive highchinery in the process.

This study focuses on journey of a specific, fluorescently-tagged a smart economy will depend on like-minded Similar to any supply chain logistics, studies across the consortium using systems functioning of a protein transport system in as well as perhaps more common Ireland industry research partnership award from 15 countries and the project is due to run Disease Diagnosis and Treatment (SysKid) research, funded through a Science throughput collaborative HPLC data analysis platform for Glycosylation is the most common andtransported “When we applied these new drugsintonew ourearly IBD partners identifying opportunities particular regulatory elements the protein as it travels through, and out of, proteins and lipids are along biology methodologies in order to develop in 2004. cilia.

This intraflagellar transport system phenotypes associated with cilium for five years. consortiumdiverse under the European FP7 of Ireland Foundation IrelandUnion President structurally post-translational the storageand andrealising annotation ofand experimental model, thethe gutpathway was tricked into the thinking that it basic applied research stage of called cytoplasmic over 8 million individual cells.” diagnostic strategies and treatment options to a complex pathway from the point of (IFT) makes contact with theinitiated ciliary through dysfunction such as and The Irish Times recognises stellar programme.ofYoung data.

The integration of next generation modification proteins.

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

This collaboration, Researcher Award Oliver The team, including postdoctoral development.

Email coat protein complexes. manufacture through stages of packaging, innovative performance Sigmoid Pharma inUCD Conway on results, the they prevent CKD obesity. gene products Blacque, have beenwere shown to beof bioinformatic tools will Based further thethese protective pathways, which in turn prevented amembrane.

SFI research supplement, highlights recently published in the researchers Dr. and Dr. Nataliafor Syskid (www.SysKid.eu) wastransportation established to through tara.mcmorrow@ucd.ie for details ofthe a PhD their many application of research development.

The UCD team, in collaboration with scilabelling and the cell potential proposed aSlattery new working model Arl13b, glycosylated.

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

He notes Arl13b associates ciliary The company two new drug Martin, utilise culture and animal position gastrointestinal currently available. further our understanding ofhas chronic glycoforms showing potential as cancer handlingwill large scale glycomics initiatives The major“That parttract,” of funding for Professor thiswith research entists in the European Molecular Biology explained working with academia can realise.” where itcell functions atdata the ciliary membrane before delivery todeveloped the kidney cell surface. technologies, LEDDS™ andto SmPill™, which membranes andScience is required forcan cilium withnot applications in biomarker discovery biomarkers, there increasing Taylor.

“Ourfrom pre-clinical trial data now has come Foundation Ireland, Laboratory (EMBL) in Heidelberg, systemOneisofanseven genes need associated with JSRDs, to regulate important ciliary membrane Taylor’s collaboration with Sigmoid Pharma NIBRT has researchers only enhance the solubility and permeability of Dr Matthew Campbell Dr Natalia structure/function in Sigmoid bothand andproduct develop high throughput, highly and inform the next phase Pharma Arl13b fornot asensitive protein already known properties such aseach shape, transmembrane network ofworms excellence, atically silenced ofbyour 22,000 genes Technology did permit scientists Thisto research was partially supported by certainly been successful these metrics with Artemenkothe whoEU-funded developed GlycoExtractor thethat drugcodes but can it toof targeted locations robust strategies detail thedeliver glycome development pipeline”. mammals demonstrates the remarkable play roles in the and/or function protein distributions and IFT.this ‘Systems Microscopy’, and the EU-FP6 Mitoto observe to what extent affected three co-authored publications to date in twothe of to catalogue thisformation journey through cell in the gastrointestinal tract, including the evolutionary conservation of how this small In addition to the product that is currently in the highest scientifica journals of cilia, which arerecently. hair-like For projections colon.

Check consortium. cell’s abilityranking to transport protein.in the organelles until the first time, Up to only 20 years ago, many believed G-protein functions.” phase II clinical studies, Sigmoid Pharma is field, Gastroenterology and Proceeding of the extending from the surface of theand cell.sophisti- They found that 15% of human genes using a combination of genetic The Sigmoid Pharma-Taylor collaboration is Reference: a LEDDS™-enabled formulation of most cilia to be redundant cellular developing National Academy of Sciences, as well as the However, the precise molecular details of Reference somehow influence theinnovative secretory pathway cated microscopy techniques, over 8cells, million facilitating the development of a new the hydroxylase generation of proprietary products organelles that have fallen victim to Simpson, J.C et al.inhibitor Genome-wide RNAi screening Glycomics needs the supporting framework tissues and fluids.

EUROCarbDB, asyndrome research infrastructure design Joubert Arl13b functions at ciliary what exactly Arl13b doing in cilia have therapeutic approach for the assessed treatment of reveal and including genes provide aoflink to other individual cells haveis been to identifies human proteins with a regulatory dimethyloxaloylglycine (DMOG) to bring about the creation ofthat high-skilled jobs. mammalian evolution a type cellular of extensive, well-curated databases and study funded by the EU 6th Framework membranes and stabilizes protein transport infunction remained unclear. inflammatory bowel disease (IBD) by bringing Commercial packages that support HPLC in the early secretory pathway.

Nature Biology, events in and around thethat cell.these cellular effective, safe and targeted delivery ofthe this thosetools. genesCurrently, that influence the transport Caenorhabditis elegans.

Cevikcan S, Hori Y, Cell Kaplan OI, Programme.

Prospective users access flexible analytical this field appendix.

We now know More than 15,000 people in Ireland and together the research methodology of the advance online publication 3 June 2012, doi: 10.1038/ instruments thethe extraction of potential therapeutic agent. theon research, Dr Kennedy tocannot die asfacilitate a result of raised New research led established,

by Conway Fellowpathway.

Dr Kida K,on Toivenon T, Foley-Fisher C, Cottell D, Katada T, network orteam secretory GlycoExtractor tool of study lacks Blacque’s the studied the gene in themost cilia likely millions antennae on nearly all of ourwith cellsCommenting ofpresent people worldwide are living the Taylor group with the proprietary available large quantities ofanalysis data.

In of anmore effortthan to alleviate glucose levels seen in diabetes.

Breandán Kennedy indicates that treatment Kontani K,Data Blacque OE. J at Cellwww.mitocheck.org Biol. 2010 22; said, “Byncb2510. establishing a robust model for Mar early From 700,000 microhttp://glycobase.nibrt.ie:8080/DemoGlycoExtra comprehensiveof and centralised data symptoms IBD today.

Current therapeutic tiny worms (Caenorhabditis elegans) and serve fundamental roles in many liquid/emulsion drug delivery system, of diabetic blindness should look at this bottleneck within high-throughput and late 188(6):953-69 stage diabetic retinopathy, we would scopy images, they found 554blood proteins that for this chronic debilitating disease are ctor/mainPage. collections, standards and “Thiscollaborators study isinformation the first genome-wide assessKennedyoptions and his team found that new LEDDS®, developed byfor Sigmoid Pharma. in the University ofDr motility and sensory functions, including protecting the while neurons responsible colour hope to better understand the progression of glycomicand projects, the NIBRT team often have very limited with surgery being the only vessels the neuronal cell death in diabetic reporting protocols that exist within influence secretion with more than 143the ment thejust secretory process in a human Reference Tokyo conducted parallel in signalling pathways to development. vision in the eye andof not targeting the disease and pave the way for identifying Commenting on the award,experiments Professor Taylor developed aviable web-based tool thatcritical interfaces option.

Theearly Sigmoid product, retinopathy can arise independently of each GlycoExtractor: A web-based interface for high genomics and cultured proteomics. influencing the stage of thecurrently secretory cell explains Conway Fellow, human cells.

Together, theyand blood vessels as issystem”, currently the practice. said, “We are1delighted Dr Coulter his new drug processing targets for successful with the Waters chromatography software May 2010.qxd:Layout copy for07/05/2010 13:12 Page 3 in a phase II clinical study, uniquely enables other. In addition, they identified that cone of its HPLC-Glycan datatreatment”. throughput It is now not surprising that defects in pathway orofmorphology ofexport the Golgi, a Natalia V. Artemenko, confirmed that Arl13b proteins uses lipid Professor Jeremy Simpson, UCD School of to oral team and indeed it reflects well package improve and automate the Researchers, Dr Natalia Artemenko and Matthew P. Campbell, and Pauline delivery a powerful drug without neurons, those involved inare Nearly 2.5 million people worldwide are Dr blindon our photoreceptor cilium structure and function associated The research was funded through Science partnership.

AThis key driver of the successful cellular structure responsible for modifying anchors tothe associate with ciliaryco-author Biology & Environmental Science, M. Rudd to Journal of Proteome Research, 2010,in 9 (4), pp causing systemic side-effects. of data vision to various file formats for subsequent Matthew Campbell from National Institute colour and used inexpanding daylight, are most due to diabetic retinopathy. secondary models identify involved early disease (CKD) and improve patient treatment, Conway researchers led by Dr. Tara Foundation Irelandprocesses and the Health Research with an ever range of human scientific research in 2010 is meaningful 2037–2041 proteins after they haveoffrom been made. CKD ofdiabetes the research paper published affected by themodular high glucose levels. complication ofmembrane. activates the growth analysis.

The architecture the tool of Bioprocessing Research & Training (NIBRT) progression and investigate novel McMorrow and Professor Michael Ryan have in Nature with particular focus on CKD arising Board.

Under normal gastrointestinal diseases and conditions, syndromes,thecollectively called interaction of in academia with industry of new leaky blood vessels the Pauline eyefunding andRudd is as that Membrane traffic connect strategies for preventing and slowing the Cell Biology. also facilitates the manipulation of data from led

by Conway Fellow, Professor diabetes and hypertension.

Thepathways multisuccessfully secured in The research team madewhich their observations Much of€485,500 theofwork on the project was carried ciliopathies, have overlapping clinical responsible for the death photoreceptors, progression of the disease. These studies will disciplinary research consortium has 25 in a carefully other data management systems. have developed an award open access, web-based membrane bound organelles part of an overall to the Systems using a novel zebrafish of diabetes, outsend

by UCD doctoral candidate, features suchmodel as polycystic kidneys and be the neurons visual messages to our Sebihapartners Reference: integrated with clinical and epidemiological (16ordered universities, 9stages industry partners) Biology towards Novel Chronic Kidney interface thatthat facilitates extraction, querying sequence to ensure the correct “In order for us to understand the impact which resembles the early of diabetic Cevik.

SheTreatment anddata her generated colleagues went onfrom to NIBRT livers, retinal degeneration, bonerun The team are now working to due integrate brain. studies across consortium using systems Predominant conethe photoreceptor dysfunction in a 15 countries and the is Disease Diagnosis (SysKid) and sharing of on HPLC-glycan in retinopathy in humans.

It of isproject an exciting complement proteins andtolipids exists theand body when this fundamental process hyperglycaemic of non-proliferative diabetic new GlycoExtractor with the EUROCarbDB biology methodologies in order to develop demonstrate in C. elegans how disrupting abnormalities, hydrocephalus, as well as Arl13bmodel at ciliary membrane for five years. consortium under the European Union FP7 high throughput processes. development for the group who now hope to Until now, it was unclear if the changes to within the cell to maintain cellular balance retinopathy.

Yolanda Alvarez, Jenneth Chen, Alison of secretion goes wrong, we must first decidiagnostic strategies and treatment options to framework to provide a comprehensive highprogramme. further extend their research and establish a vessels and neurons occurred independently of Reynolds,CKD Nore development.

Waghorne, John Email J. O’Connor, Breandan The UCD Conway team,analysis including postdoctoral or homeostasis. prevent pher functional network of membrane Glycosylation the the most throughput HPLC platform for model of late stagedata diabetic disease. one other and is which type common of retinal and neuron is Kennedy. Disease Models & Mechanisms (2010) Dr. Craig Slattery Dr. Natalia Syskid (www.SysKid.eu) was established tara.mcmorrow@ucd.ie for details of silenced a PhD (middle, In cells where different genes are trafficking pathways withintothe cell. researchers structurally diverse post-translational the storage and annotation of and experimental will utilise cellofculture and animaland lipids in position currentlytheavailable. further our understanding of chronic kidney site where the secretory processes begins Newly proteins the bottom), modification ofMeta-analysis proteins. More of all led Martin, data. The integration next generation bythan UCDhalf researchers by of HIV nef are critical in determining rate studies synthesised in humans have shown that non (green) changes compared to normal cellsthe (top). gene products Conway have been shown to be Denis Shields bioinformatic tools will was further the Fellow, Professor has of disease progression. Professor Denis progression associated with gross glycosylated. With many specific glycans developmentdeletions of unified approaches determined that there is no or clear evidence Shields believes that searches for modifiers of in the nef gene. for glycoforms showing potentialdefective as cancer large glycomics data initiatives viral you sequences in progression rates should focus onMSc otherin larger programmes suchnow as the new We scale introduced 4 new advanced core Ithat amparticular delighted to welcome to thehandling However, much of the research in the area to the is HIV-1 nef gene certain ofwith the applications host and commencing viral factors. “Systematic evaluation biomarkers, there an Focus increasing need to regions in biomarker discovery technology modules onobservational a pilot basis or this Conway andorlook forward to working Imaging in September 2010. date has been based on case protein playhighly a significant role in disease of largeDrquantities of data by Matthew Campbell andbioinformatics Dr Natalia develop high throughput, sensitive and academic year;than those covering principlesNIBRT researchers studies rather rigorous, systematic with you in the coming months!

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

This work by doctoral Glycomics needsthat the detail supporting framework cells, tissues and fluids.

EUROCarbDB, a research infrastructure design and practical aspects of imaging and applied Ihypotheses hope that athat number of new are in initiatives, the literature, tract is lined with cellscurrent that block the contents results in both academic outputs anda the Irish biopharmaceutical development Welcome!

UCD Conway Institute willset have As the international spotlight turns to as HIV-infected patients can and be categorised on candidate Ravindra Pushker out topresence of extensive, well-curated databases study funded by the EU 6thunknown Framework proteomics began in late March and will run it is in discovering patterns”, heInsaid. of the gut from leaking into the intestine. an application of research toward clinical product company, Sigmoid Pharma recently scooped As an institute with an increasingly including the early-stage researcher forum Commercial packages that support HPLC at the event part of thelarger University’s focusProspective on Irish science, amaccess delighted the basis of Currently, the numberthis of years determine in aas substantially sample set flexible analytical tools. field it takes for Programme. users Ican the to until mid-June with furthercompanies.” twoofmodules in IBD patient,inthis barrier is will broken the development with indigenous the overall Innovation of the Yearand award at facilitate theaWe extraction interdisciplinary research focus described this issue, not and only issue coincides with preparations for research showcase. look forward see impact of Conway research as our them to progress to AIDS. Some patientsinstruments ifcannot any association exists between diseaseto GlycoExtractor Thisthe research was funded through Science tool on of study lacks This the established, contents of the gut leak out into surrounding the inaugural Irish Times All-Island large quantities of data.

Inflow an effort toamino alleviate genomics and cytometry taking place maintain stable CD4 lymphocyte counts and progression and particular acid of Foundationcontinue Ireland and College comprehensive and centralised data http://glycobase.nibrt.ie:8080/DemoGlycoExtra Commenting on the Taylor collaboration, Dr expertise inAwards. specialist platforms, the Euroscience Open Forum Dublin 2012bottleneck presenting the quality and breadth our scientists to University publish in highlyused strengthen the community of Conway areas.

The research team in UCD Conway Innovation Thetechnology life-science SME, this within high-throughput over week-long periods during the summer do not go on to develop AIDS even after more differences or deletions within the nef gene.

Dublin. journals. In particular, I would like collections, standards and information ctor/mainPage.

Coulter said, “The collaboration with the Taylor when whopharmacology most to influence science, research programme as well as highlighting regarded we arethose uniquely placed participate inglycomic the a model of IBD and, by applying a new class of founded

by UCD graduate, Dr researchers and forge new interdisciplinary projects, the NIBRT team have than 10 years of within infection. reporting protocols that exist months. clearly demonstrates the potentialReferencedrugs known as hydroxylase inhibitors, were laboratory Ivan Coulter, has actively collaborated with society and policy will arrive in the capital the technology expertise and to congratulate Professor Jeremy Simpson On acore per patient basis, there was no excess of developed a web-based tool that interfaces education and training of the next links but will celebrate and heighten GlycoExtractor: A web-based interface for high genomics and proteomics. that can be realised through focused able to almost completely reverse the article Conway Fellow, Professor Taylor Scientists are curious as to Cormac why these longLTNPchromatography patientsservice with one or more to defective nef with the Waters software the largest open forum its The kind. customised available academics on his Nature Cellresearch Biology research throughput processing of HPLC-Glycan generation of research scientists. newlylikely application basicofresearch.

The development awareness our and innovation on the Drdata Kennedy most to die as and atoof result the raised New research for led bynonConway Fellow DrDr of We hope determine from this pilot if Commenting ofofresearch, the disease. since being granted aand Science Foundation term, progressor (LTNP) patients do not sequences when compared to progressors. package to improve automate the export Researchers, Dr Natalia Artemenko Artemenko, Matthew P. Campbell, and Pauline Natalia V. symptoms It is anticipated that the international and industrial partners in conjunction with that is highlighted in this issue. of a smart economy will depend on like-minded glucose levels seen in diabetes.

Breandán Kennedy indicates that treatment said, “By establishing a robust model for early Reference: launched PhD programme in Bioinformatics M. Rudd Journal of Proteome Research, 2010, 9 (4), pp successes.

Ireland industry research partnership award develop AIDS. This mayInstitute reflect differences While the high frequency ofwithin aminoUCD acid as well Matthew Campbell from the National of in data to various filefor formats for subsequent demand training from “When we applied these new we drugs to nef ouramino IBD collaborative partners identifying opportunities Meta-analysis to test the association of would HIV-1 conference attract more than 5,000 our dedicated core technology directors 2037–2041 of Bioprocessing diabetic blindness should look atrecently and late stage diabetic retinopathy, in the2004. host, viralwill genetics or(NIBRT) environmental replacement at particular residues is indicative of Research &Biology Training The modular architecture of the tool and Systems attractedanalysis.

80 as from external academic centres and acid differences and deletions with disease progression.

Dr Kennedy and his team found that new blood model, the gut was tricked into thinking that it and realising basic and applied research business leaders, government and their staff.

Professor Walter Kolch protecting the scientists, neurons responsible for colour factors that could potentially be exploited for of rapid evolvement, permutation testing led

by Conway Fellow, Professor Pauline Rudd also facilitates the manipulation of data from hope to better understand the progression of Theand Irish120 Times awardapplicants recognisesfor theup stellar Ravindra Pushker, Jean-Marc Jacquē,This Denisactivated C. Shields.

Professor Walter Kolch EU non-EU to 15 andsynergies. industry will stand-alone delivery of was being deprived of oxygen.

Thisdictate collaboration, initiated through vessels the neuronal cell death in diabetic officials and media.

Director visiondeveloped in the eye not just targeting the the treatment of the disease. showed that residues Journal Virology, 2010 p3644-3653 have anand open access, web-based other systems.with more replacements the disease andofpave theApr way for identifying innovative performance of Sigmoid Pharma in data management protective pathways, which in turn prevented athese SFI arise research supplement, highlights thewithin retinopathy can independently of each advanced modules or inclusion Director, UCD Conway Institute studentships. than expected were not statistically significant. interface that facilitates extraction, querying blood vessels their as isapplication currently the practice. research and new drug forthe itscells successful thetargets death of that linetreatment”. the potential that innovative indigenous Studies in modeloforganisms havedevelopment. shownThe thatNIBRT team are now workingthat to integrate other.

In addition, they identified cone companies and sharing of The HPLC-glycan datadeveloped generated in new drug company has two gastrointestinal tract,” explained Professor working with academia canthat realise.” infection with nef-deficient virus shows an Theneurons, researchers conclude current data GlycoExtractor with the EUROCarbDB photoreceptor those involved in Nearly 2.5 million people worldwide are blind high throughput processes. LEDDS™ and SmPill™, which not The research through technologies, Taylor.was “Ourfunded pre-clinical trial Science data can now provides noa evidence that individual course of infection and someframework to provide comprehensive high- residues colour and used in daylight, most due to diabeticattenuated retinopathy.

Thissolubility secondary Taylor’s collaboration withare Sigmoid Pharma Foundation has the of vision Ireland andphase the Health Research inform the next Sigmoid Pharma product throughput HPLC data analysis platform for Glycosylation isonly theenhance most common and and permeability affected by certainly the highbeen glucose levels. by these metrics with complication ofthe diabetes activates the itgrowth successful drug but can deliver to targeted locations Board. development pipeline”. the storage and annotation of experimental structurally diverse post-translational three co-authored publications to date in two of of new leaky blood in the eye andincluding is in thevessels gastrointestinal tract, the

Worm research reveals cilia disease gene functionAward Conway collaborator scoops Irish Times Innovation Tracking the secretory pathway in cells

Success in EU FP7 call

GlycoExtractor advances glycan data manipulation

Zebrafish model gives insights into diabetic blindness

Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Director’s Message

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

Zebrafish model gives insights into diabetic blindness

UCD CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH

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Conway collaborator Irishembryo Times Innovation Identifying proteins critical scoops to bovine survival Award

Conway collaborator scoops Irish Times Innovation Award collaborator scoops Irish Times Innovation Award Gremlin Conway key to tackling pulmonary hypertension Irish biopharmaceutical development company, Sigmoid Pharma recently scooped UCD researchers havedevelopment identified, for Irish biopharmaceutical the overall Innovation of therecently Year award at company, Sigmoid Pharma scooped the first time, a molecular mechanism the Irish All-Island the inaugural overall Innovation of the Year vascular award at that accounts forTimes the unique Innovation Awards.

The life-science the inaugural Irish Times All-Island SME, remodelling of the pulmonary founded

by Awards.

UCD pharmacology graduate, Innovation The life-science SME, circulation in response to hypoxia orDr Ivan Coulter, haspharmacology actively collaborated with founded by UCD graduate, Dr low levels of oxygen.

Conway Fellow, Cormac Taylor Ivan Coulter, hasProfessor actively collaborated with Conway Fellow, Professor Taylor since being granted a Science The findings, published inCormac theFoundation journal, since being granted a Science Foundation Ireland industry research partnership award Circulation may focus efforts in tackling Ireland research partnership award in 2004.industry pulmonary hypertension, a feature in 2004. of chronic hypoxic diseases The Irish Times awardlung recognises thesuch stellar Thechronic Irish Times award recognises stellarin as obstructive innovative performance ofpulmonary Sigmoidthe Pharma innovative performance of Sigmoid Pharma in disorder (COPD) emphysema their application of and research and development. theircompany application research development. that significantly impactsand on The hasofdeveloped twopatient new drug The company has developed two new which drug not morbidity & LEDDS™ mortality. technologies, and SmPill™, technologies, LEDDS™ and and SmPill™, which not only enhance the solubility permeability of May 2010.qxd:Layout 1 07/05/2010 only enhance thecopy solubility and permeability13:12 of First author and PhD candidate, the drug but can deliver it to targetedEdwina locations the drug but can that deliver it to targeted Cahill explains “diseases suchlocations as in the gastrointestinal tract, including the in the gastrointestinal tract, including the emphysema, chronic bronchitis and colon. colon. of the lungs cause abnormally fibrosis low Sigmoid levels of oxygen in thecollaboration lung. Whenis The The Sigmoid Pharma-Taylor Pharma-Taylor collaboration is the lung isthe starved of oxygen, blood facilitating development of aa new new facilitating the development of pressure inapproach the arteries of treatment the lung of therapeutic for the therapeuticcausing approachdamage for the treatment of increases to blood inflammatory bowel disease (IBD) (IBD) by bringing bringing inflammatory bowel disease by vessels and making it more difficult together the methodology of of the the together the research research methodology for the heart to pump blood. In many Taylor group with the proprietary cases, this can lead to heart failure and liquid/emulsion drug delivery system, premature death”.

LEDDS®, developed by Sigmoid Pharma.

Commenting on the award, Professor Taylor said, “We are delighted for Dr Coulter and his team and indeed it reflects well on our partnership. A A key key driver driver of partnership. of successful successful scientific research research in in 2010 scientific 2010 is is meaningful meaningful Irish biopharmaceutical development interaction of academia academia with industry that interaction of with recently industry that It is not currently possible to predict company, Sigmoid Pharma scooped

results in both academic outputs and the application of research toward clinical product While investigating the factors that results in both academic outputs and the development indigenous companies.” contribute high blood pressure the application oftowith research toward clinical in product arteries, the on UCD team found that, with development indigenous companies.”

Commenting with the Taylor collaboration, Dr

reduced oxygen levels in the lung, the Coulter said, “The collaboration with the Taylor Commenting on the Taylor collaboration, body produces elevated quantities ofDr a laboratory clearly demonstrates potential Coulter said, “The collaboration with the Taylor protein called gremlin, whichthe suggests a that between can beclearly realised through focused laboratory demonstrates thegremlin potential link elevated levels of application of basic research.

The development that can be realised through focused and pulmonary hypertension.

application of basic research.

Theon development of a smart economy will depend like-minded

of a smart economy depend like-minded collaborative partners identifying opportunities The research team will focused onon gremlin 1 collaborative partners identifying opportunities and realising basic applied research given its ability toand efficiently block the and realising basic and appliedinitiated research synergies. collaboration, through actions of This the BMP signalling pathway in synergies.

This collaboration,highlights initiated through a SFI research supplement, the pulmonary hypertension. apotential SFI research supplement, highlights the that innovative indigenous companies

potential that innovative indigenous companies workinghypoxic with academia can realise.”

Under conditions, gremlin 1 working with academia can realise.” expression is increased as is its secretion Taylor’s collaboration with Sigmoid It Pharma has from the Page 3vascular endothelium.

Taylor’s collaboration with Sigmoid Pharma has certainly BMP been signalling successful and by these metrics with inhibits contributes certainly been successful by these metrics with three co-authored publications to date in two of to theco-authored development of pulmonary three publications to date in two of the highest ranking scientific journals in the hypertension. the highest ranking scientific journals in the

field, Gastroenterology Gastroenterology and and Proceeding Proceeding of of the the field,

National Academy Academy of Sciences, Sciences, as well well as as the the Conway Fellow, Professor Paul National of as generation of of who proprietary innovative products McLoughlin led the project believes generation proprietary innovative products that, “Given that hypoxia induced and the the creation of high-skilled high-skilled jobs. and creation of jobs. increase in gremlin 1 is selective for the More than than 15,000 people in Ireland Ireland and More 15,000 in and lung, it offers an people attractive potential millionsfor of therapy people worldwide worldwide are living livingits with the the millions of people are with target as antagonising symptoms today.

Currenteffects therapeutic therapeutic action mayIBD have minimal in other debilitating disease disease are are options for this chronic debilitating organs.”

tract is lined with cells that block the contents of theisresearch gut from leaking intoblock the intestine.

In an This was funded primarily tract lined with cells that the contents IBD this barrierResearch is broken and theand through Health Board of thepatient, gut the from leaking into the intestine.

In an contents of the leakIreland. into surrounding Science Foundation IBD patient, thisgut barrier isout broken and the areas. The team in into UCDsurrounding Conway used contents of research the gut leak out aReference model ofresearch IBD and,team by applying new class areas.

The in UCD aConway usedof Cahill, E et al. Gremlin Plays a Key Role in the known asand, hydroxylase inhibitors, wereof adrugs model of IBD by applying a new class Pathogenesis of Pulmonary Hypertension. Circulation able toknown almostasonline completely reverse the13, were drugs hydroxylase inhibitors, (2012) Published before print January 2012, doi: able to almost completely symptoms of the disease. reverse the 10.1161/​ circulationaha.111.038125 symptoms of the disease.

“When we applied these new drugs to our IBD “When newinto drugs to ourthat IBDit model, we theapplied gut wasthese tricked thinking model, the deprived gut was tricked into This thinking that it was being of oxygen. activated was being deprived oxygen.

This prevented activated protective pathways,ofwhich in turn protective pathways, in turn the death of the cellswhich that line the prevented the death of the tract,” cells that line theProfessor gastrointestinal explained gastrointestinal tract,” explained Taylor. “Our pre-clinical trial dataProfessor can now Taylor. “Our pre-clinical trial data can now inform the next phase Sigmoid Pharma product inform the next phase Sigmoid Pharma product development pipeline”. development pipeline”.

In addition to the product that is currently in In addition to the product that is currently in phase clinical studies, studies, Sigmoid Sigmoid Pharma Pharma isis phase IIII clinical developing aa LEDDS™-enabled LEDDS™-enabled formulation formulation of of developing the hydroxylase hydroxylase inhibitor inhibitor the dimethyloxaloylglycine (DMOG) (DMOG) to to bring bring about about dimethyloxaloylglycine Representative image of immunofluorescent effective, safeconfocal and targeted targeted delivery of this this effective, safe and delivery of (FITC) staining of gremlin showing labelling in the potential therapeutic agent. potential therapeutic agent. alveolar wall is suggestive of localisation predominantly in the capillary endothelium.

very limited with surgery often often being being the the only only viable option. The Sigmoid product, product, currently currently in a phase II clinical study, uniquely uniquely enables enables oral delivery of a powerful drug drug without without causing causing systemic systemic side-effects. side-effects.

Predicting toxicity in the drug development Conway collaborator scoops Irish Timespipeline Innovation Award accurately and at anofearly stage the overall Innovation the Year award at whether there are toxicity issues with the inaugural Irish Times All-Island Innovation Awards.

The life-science SME, candidate drugs. This shortcoming of founded by UCD pharmacology graduate, Dr existing toxicology evaluation methods Ivan not Coulter, actively collaboratedinwith can onlyhas create a bottleneck the Conway Fellow, Professor Cormac drug development pipeline butTaylor can since being granted Science Foundation sometimes lead toa the withdrawal of Ireland industry research partnership award drugs from the market.

resultsnormal in bothconditions, academic outputs and the Under the gastrointestinal Underliterature normal conditions, from sources. the gastrointestinal

application of research toward clinical product development with indigenous companies.”

The team developed and optimised a Commenting on the Taylor collaboration, Dr selected reaction monitoringwith assay Coulter said, “The collaboration the(SRM) Taylor in order toclearly quantify the proteins in this laboratory demonstrates the potential putative biomarker panel. focused This revealed that can be realised through aapplication panel highly enriched for The proteins that of basic research. development had been changed significantly a result of a smart economy will depend onas like-minded of toxicant exposure. collaborative partners identifying opportunities

tract is lined with cells that block the contents disease With of the gutand fromarthritis. leaking into thesupport intestine. In an from Agilent weand arethe now IBD patient, thisTechnologies, barrier is broken establishing dedicated to contents of theagut leak out laboratory into surrounding areas.

The research team in UCDvalidation Conway used undertake these SRM-based astudies.” model of IBD and, by applying a new class of drugs known as hydroxylase inhibitors, were able to almost completely reverse the Reference of the disease. symptoms Collins, BC et al; Development of a pharmaceutical hepatotoxicity biomarker panel using a discovery “When we applied these new drugs to ourtoIBD of HIV the nef are was critical in determining thethat rateit targeted proteomics approach.

Molecular & Cellular model, gut tricked into thinking of HIV nef are critical in determining the rate of disease progression.

Professor Proteomics doi: 10.1074/mcp.M111.016493 was being (2012) deprived of oxygen.

This Denis activated of disease progression.

Professor Denis of Shields believes thatwhich searches for modifiers protective pathways, in turn prevented Shields that searches for modifiers the deathbelieves of the cells that line progression rates should nowthe focus on otherof progression should now focus on other gastrointestinal tract,” explained Professor host and viralrates factors.

“Systematic evaluation Taylor.

“Our pre-clinical trialbydata canevaluation now host and viral factors.

“Systematic of large quantities of data bioinformatics inform next phase Pharma product of large quantities of Sigmoid datainby bioinformatics can bethe just as important refuting development pipeline”. can be just as important in refuting hypotheses that are current in the literature, as

Bioinformatic analysis Bioinformatic analysis of of HIV HIV progression progression studies studies in 2004.

Meta-analysis

by UCD researchers led by Meta-analysis by UCD researchers led by

The IrishFellow, Times award recognises the stellar Conway Professor Denis Shields has UCD researchers have reported in Conway Fellow, Professor Denis Shields innovative performance ofno Sigmoid Pharmahas in determined that there is clear evidence Molecular & Cellular Proteomics on a their application of research development. determined thatdefective there is viral no and clear evidence that particular sequences in proof-of-principle study that may The company developed new benefit drug that particular defective viraltwo sequences in the HIV-1 nef has gene or industry certain regions of the the pharmaceutical in thewhich future technologies, LEDDS™ and SmPill™, not the HIV-1 nefagene or certain regions of the protein play significant role in disease by providing a roadmap for large scale only enhance the solubility and permeabilitypreof protein play a significant role in disease progression. clinical biomarker verification the drugtoxicology but can deliver it to targeted locations progression. studies. in the gastrointestinal tract, theon HIV-infected patients can beincluding categorised colon. the basis of the number it takes on for HIV-infected patients canofbeyears categorised

The study involved theofmolecular profiling them to progress to AIDS. Some The Sigmoid Pharma-Taylor collaboration is the basis of the number years itpatients takes for of models that hadlymphocyte been exposed to facilitating the development of a new maintain stable CD4 counts them to progress to AIDS. Some patientsand known toxic insults in AIDS an to derive therapeutic for theeffort treatment ofand do not go onapproach to develop even after more maintain stable CD4 lymphocyte counts the signatures. inflammatory disease (IBD) by bringing thanassociated 10 years bowel of biomarker infection. do not go on to develop AIDS even after more together the research methodology of the than 10group years of infection.

Scientists arecandidate curious as biomarkers to why theseof longTaylor with the proprietary Forty-eight liquid/emulsion drug delivery system, term, nonprogressor (LTNP) patients liver toxicity were from longado not Scientists are curiousassembled as to why these LEDDS®, developed

by Sigmoid develop AIDS. This may reflect differences in discovery screen ofPharma. liverdo not term, non- proteomics progressor (LTNP) patients theahost, viralon genetics or environmental in hepatotoxicant treated rat model Commenting the award, Professor Taylor develop AIDS. This may reflect differences in factors thatarecould potentially exploited using label free liquid chromatography said, “We for Drbe Coulter and for his the host, viral delighted genetics or environmental the treatment of the disease. mass spectrometry (LC-MS); a previous team and indeed it reflects well on our factors that could potentially be sample exploitedand for transcriptomics partnership. A keystudy driver of of the successful Studies inresearch model organisms shown that the treatment of the scientific indisease.

2010 ishave meaningful infection with nef-deficient shows an interaction of academia withvirus industry that Studies in model attenuated courseorganisms of infectionhave andshown some that infection with nef-deficient virus shows an attenuated course of infection and some

studies in humans haveapplied shownresearch that non and realising basic and studies in humans have shown that non progression was associated with synergies.

This collaboration, initiated through Dr Ben Collins, first authorwith andgross Agilent progression was associated gross deletions in the nef gene. a SFI research supplement, highlights the UCD Newman Fellow, explains, “The deletionsthat in the nef gene. potential innovative indigenous and companies idea was to use However, much oftranscriptomics the research in the area to working with academia can realise.”

proteomics and combine the data However, much oftothe in the area to date has been based onresearch observational or case to provide earlier markers of toxicity.

Taylor’s with Sigmoid Pharma has date hascollaboration been based on observational or case studies rather than rigorous, systematic certainly been by these Although thissuccessful study focused on one with studies rather than rigorous, systematic scientific evaluation.

This work by metrics doctoral three co-authored publications to is date in two of hepatotoxic compound, there sufficient candidate Ravindra Pushker set by outdoctoral to scientific evaluation.

This work the highestin ranking scientific used journals in the flexibility the approach to allow determine in a substantially larger sample set candidate Ravindra Pushker set out to field, Gastroenterology and Proceeding medium toinhigh throughput fordisease largeof the ifdetermine any association exists between a substantially larger sample set National Academy of Sciences, as well as the scale verification studies amino involving large progression particular acid if any association exists between disease generation ofand proprietary innovative products numbers of well-defined toxicants and differences orand deletions within the nef gene. and the creation of high-skilled jobs. progression particular amino acid ultimately for more sensitive toxicology differences or deletions within the gene.of More thanpatient 15,000 people in Ireland and On a per basis, there was nonef excess evaluation for drugs under early millions of people worldwide are defective living withnef the development.”

LTNP patients with one or more On a per patient basis, there was no excess of symptoms today.

Current sequences IBD when compared totherapeutic progressors.

LTNP patients with one or more defective nef

options forhigh thisand chronic debilitating disease are While leader the frequency of amino author, acid Team corresponding sequences compared to progressors. very limited when with surgery often being the only replacement at particular residues is indicative Professor Steve Pennington adds, “We While option. the highThe frequency amino acid viable Sigmoidofproduct, currently of rapid evolvement, permutation testing are now working to extend this approach in a phase II clinical study,residues uniquelyisenables replacement at particular indicative showed that residues with drug more replacements to more readily accessible sample types oral delivery of a powerful without of rapid evolvement, permutation testing such as systemic bloodwere and are applying itsignificant. in other than expected not statistically causing side-effects. showedto that residuesdiagnostics with more replacements studies develop for chronic The conclude thatcardiovascular current data thanresearchers expected were statistically significant.

Under normal conditions, the gastrointestinal conditions such as not cancer,

is in discovering patterns”, heinsaid. areunknown current literature, as Inithypotheses addition tothat the product thatin isthe currently phase clinical studies, Sigmoid Pharmaheissaid. it is inII discovering unknown patterns”, This research was funded through Science developing a LEDDS™-enabled formulation of Foundation Ireland and University This research was funded throughCollege Science the hydroxylase inhibitor Dublin. dimethyloxaloylglycine to bring about Foundation Ireland and(DMOG) University College effective, Dublin. safe and targeted delivery of this potential therapeutic agent.

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

Meta-analysis to test the association HIV-1C.nef amino Ravindra Pushker, Jean-Marc Jacquē,ofDenis Shields.

Professor Pennington with Dr Ben acid differences andApr deletions with disease progression.

Journal ofSteve Virology, 2010pictured p3644-3653 Collins, UCD NewmanJacquē, Fellow Denis (now based at the RavindraAgilent Pushker, Jean-Marc C. Shields.

Journal of AprSystems 2010 p3644-3653 Institute ofVirology, Molecular Biology, ETH Zurich).

provides no evidence that individual residues The researchers conclude that current data provides no evidence that individual residues

Bioinformatic analysis of HIV progression studies

Irish biopharmaceutical development UCD researchers led by Conway Fellow, company, Sigmoid Pharma recently for scooped Professor Mark Crowe describe, the the overall Innovation the Year award at first time, the proteinoflandscape of the the inaugural Irish Times uterine environment in All-Island any domesticated Innovation Awards.

The life-science SME, species before implantation.

results in both academic and the be a promising source ofoutputs biomarkers of application of research toward clinical product uterine function.

Success in EU FP7 call development with indigenous companies.”

Success in EU FP7 call Describing the Dr Giuliano Elia, UCD Commenting onstudy, the Taylor collaboration, Dr

Conway Proteomics Core Director said, Coulter said, “The collaboration with the Taylor foundedresearchers

by UCD pharmacology graduate, Dr “Using label-free liquid chromatographydisease (CKD) anddemonstrates improve patient treatment, Conway led by Dr. Tara laboratory clearly the potential Ivan Coulter, has actively collaborated with With more than 30% of reproductive failure tandem mass spectrometry, we McMorrow and Professor Michael have with particular focus on CKD arising from May 2010.qxd:Layout 1 copy 07/05/2010 13:12 disease Page 3 realised that can be through focused (CKD) and improve patient treatment, Conway researchers led by Dr. TaraRyan Fellow, Professor Taylor inConway mammals arising due toCormac the loss of an performed shotgun proteomics of the diabetes andof hypertension.

The multiapplication basic research.

The development successfully secured €485,500 inRyan funding as McMorrow and Professor Michael have with particular focus on CKD arising from since being granted a Science Foundation embryo in the preimplantation period, bovine histotroph proteome aton two25key of a smart will depend disciplinary research consortium haslike-minded of an award to thethe Systems diabetes andeconomy hypertension. successfully secured €485,500 in funding as Ireland industry research partnership award itpart is vital tooverall understand how uterine preimplantation stages ofThe themultiestrous cycle collaborative partners identifying opportunities partners (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney disciplinary research consortium has 25 part of an overall award to Systems in 2004. environment functions tothe support the inand high fertility cattle.

We examined the realising basic and applied research from 15 (16 countries and the project ispartners) due todays run Diseasetowards Diagnosis and Treatment (SysKid)of partners universities, 9 industry Biology Novel Chronic Kidney embryo early establishment proteomic changes occurring between The Irishduring Times the award recognises the stellar synergies.

This collaboration, initiated five from 1513years. countries andspecific the project is duethrough to run consortium under the Union FP7 in Disease Diagnosis andEuropean Treatment (SysKid) pregnancy.

7for and to identify proteins likely innovative performance of Sigmoid Pharma a SFI supplement, highlights the for fiveresearch years. to consortium underofthe European FP7 programme. to contribute embryo survival.” their application research andUnion development. potential innovative indigenous companies The UCD that Conway team, including postdoctoral programme.

As the sole supply of vitamins, minerals, The company has developed two new drug working withDr. academia can realise.”

The UCD Conway team,Slattery including postdoctoral researchers Craig and Dr. Natalia Syskid (www.SysKid.eu) was established to enzymes and LEDDS™ other nutrients for thewhich not Functional analysis of 34 differentially technologies, and SmPill™, researchers Dr. Craig Slattery and Dr. Natalia Syskid was to Martin, utilise cell culture and animal further(www.SysKid.eu) our understanding of established chronic kidney developing conceptus before implantation, expressed proteins revealed distinct Taylor’s will collaboration with Sigmoid Pharma has only enhance the solubility and permeability of will utilise cell culture and animal further our understanding secretions) of chronic kidney the is critical Martin, biological rolessuccessful believed by to these be involved certainly been metrics with the histotroph drug but can(uterine deliver it to targeted locations for survival of the early embryo and may inthree early pregnancy.

These included co-authored publications to date in two of in the gastrointestinal tract, including the 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 high-skilled jobs. cells, tissues andoffluids.

Glycomics needs the supporting framework inflammatory bowel (IBD) by bringing cells, tissues and fluids.

Glycomics needs the disease supporting framework oftogether extensive, well-curated databases and More than 15,000 people Ireland HPLC and the well-curated research methodology the of extensive, databasesofand Commercial packages thatinsupport flexible analytical tools.

Currently, this field Commercial packages that support HPLCwith the millionsProfessor of people worldwide are extraction living Taylor group withdiagnosing the proprietary flexible analytical tools.

Currently, this TB field instruments cannot facilitate the Fellow, Sean Callanan outlined Problems with bovine results in both academic outputs and the ofof Irish biopharmaceutical development instruments cannot facilitate thetherapeutic extraction of study lacksthe the established, symptoms IBD today.

Current liquid/emulsion drug delivery system, of study lacks established, aapplication method of safely manipulating large quantities ofdata. data.

Inan aneffort effort toblood alleviate in cattle infected with the common of research toward clinical product company, Sigmoid Pharma recently scooped large quantities of In todisease alleviate comprehensive and centralised data options in forthe thisbrain chronic debilitating are LEDDS®, developed

by Sigmoid Pharma. comprehensive and centralised data vessels to reduce cerebral livestock disease, liver fluke, may this bottleneck within high-throughput development with indigenous companies.” the overall Innovation of the Year award at this within high-throughput collections,standards standardsand andinformation information verybottleneck limited with surgery often being the only collections, oedema. be contributing to the spread of glycomic projects, the NIBRT team have the inaugural Irish All-Island Commenting on theTimes award, Professor glycomic projects, the NIBRTproduct, team have reporting protocols that exist within Taylor viable option.

The currently reporting protocols that exist within Commenting on theSigmoid Taylor collaboration, Dr bovine TB, according to Dr new research developedaaweb-based web-based tool thatinterfaces interfaces Innovation Awards.

The for life-science SME, said, “We are delighted Coulter and his developed tool that genomics and proteomics. in a phase II “The clinical study, uniquely enables genomics and proteomics.

Coulter said, collaboration with the published in Nature Communications By allowing periodic opening of tightTaylor with the Waters chromatography software founded UCD pharmacology graduate, Dr team andbyindeed it reflects well on our with the Waters chromatography software oral delivery of a demonstrates powerful drugcells without laboratory clearly the potential involving Conway Fellow, Professor junction channels between lining package to improve andautomate automate the export Researchers, Natalia Artemenko andDr Dr Ivan Coulter, has actively with partnership.

ADr key driver ofcollaborated successful Researchers, Dr Natalia Artemenko and package to improve and the export causing systemic side-effects. that can be realised through focused Grace Mulcahy. the blood vessels in the brain, the Conway Fellow, Professor Taylor scientificCampbell research in 2010 is meaningful datatotovarious variousfile fileformats formatsfor forsubsequent subsequent Matthew Campbell from theCormac National Institute Matthew from the National Institute ofofdata application of basic research.

The development blood in the brain Under vessels normal conditions, thebecome gastrointestinal since beingof granted a Science Foundation interaction academia with industry that of Bioprocessing Research Training (NIBRT) analysis.

Themodular modular architecture thetool tool of Bioprocessing Research &&Training (NIBRT) analysis.

The architecture ofofthe of a smart economy will depend on like-minded marginally and reversibly permeable to A study of 3,000 dairy herds in England Ireland industry research partnership award led also ledby byConway ConwayFellow, Fellow,Professor ProfessorPauline PaulineRudd Rudd alsofacilitates facilitatesthe themanipulation manipulationofofdata datafrom from collaborative partners tiny molecules.

Thisidentifying allows theopportunities fluid in and Wales found that liver fluke infection in 2004. have developed other data systems. have developedan anopen openaccess, access,web-based web-based other datamanagement management systems. and realising basic and applied research the brain, largely comprising water, to reducesthat thefacilitates sensitivity of skin tests used interface extraction, querying interface that facilitates extraction, querying Thediagnose Irish Times awardTB recognises the stellar synergies. initiated through efficiently drain back into the blood. to bovine (BTB).

The team are now working totointegrate TheNIBRT NIBRTThis teamcollaboration, are now working integrate and sharing of data and sharingperformance of1HPLC-glycan HPLC-glycan datagenerated generated innovative Sigmoid Pharmain in May 2010.qxd:Layout copy of07/05/2010 13:12 Page 3 aGlycoExtractor SFI research supplement, highlights the GlycoExtractor with the EUROCarbDB with the EUROCarbDB high theirthroughput application processes. of research and development. high throughput processes. potential innovative indigenous companies The teamthat also observed cognitive framework to aacomprehensive highConsequently, cattle infected with both framework toprovide provide comprehensive highThe company has developed twoTara drug disease (CKD) and improve patient treatment, Conway researchers led Dr. working with academia can models realise.” improvement indata murine of focal Glycosylation is the most common and throughput HPLC analysis platform for liver fluke and BTB mayby not benew identified Glycosylation is the most common and throughput HPLC data analysis platform for technologies, LEDDS™ and SmPill™, which not McMorrow and Professor Michael Ryan have with particular focus on CKD arising from cerebral oedema after administering short the and annotation ofofexperimental structurally by existingdiverse bovinepost-translational TB surveillance thestorage storage and annotation experimental structurally diverse post-translational Taylor’s collaboration with Sigmoid Pharma has only enhance the solubility and permeability of diabetes and hypertension.

The multisuccessfully secured €485,500 in funding as interfering RNA directed against claudindata.

The integration ofofnext generation modification of proteins.

More than half ofofall schemes and may continue transmitting data.

The integration next generation modification of proteins.

More than half all certainly been successful by these metrics with Meta-analysis by UCD researchers led by studies in humans have shown that non the drug but can deliver it to targeted locations disciplinary research consortium has 25 part an overall award to the their Systems 5.

BTBof ifproducts they are moved from bioinformatic tools will further the gene products have been shown to befarm of gene have been shown toShields bethe has bioinformatic toolsassociated will further thedate three co-authored publications to in two of Conway Fellow, Professor Denis progression was with gross in the gastrointestinal tract, including partners (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney origin. glycosylated. With many specific glycans or development of unified approaches for glycosylated.

Withthere many specific glycans or development of unified approaches forin the the highest scientific journals determined that no clear evidence deletions inranking the nef gene. from 15 countries and the project is due to run Disease Diagnosis and is Treatment (SysKid) colon.

These observations may have glycoforms showing potential as cancer handling large scale glycomics data initiatives field, and Proceeding of the that particular defective viralas sequences for fiveGastroenterology years. glycoforms showing cancerFP7in handling large scale glycomics data initiatives consortium under thepotential European Union consequences for early intervention in biomarkers, there is an increasing need to with applications in biomarker discovery In the same issue, a collaborative However, much of the research in the area The Pharma-Taylor collaboration is programme.

National ofbiomarker Sciences, as well as theto the Sigmoid HIV-1 nef gene regions the biomarkers, there is or an certain increasing need of toand withUCD applications in discovery cases ofAcademy traumatic brain injury, or indeed The Conway team, including postdoctoral develop high throughput, highly sensitive research study that included Conway date has been based on observational or case facilitating the development of a new generation of was proprietary innovative products protein high play throughput, a significanthighly role in diseaseand This research partially supported by develop sensitive any neurological condition where cerebral researchers Dr.was Craig Slattery and Dr. Natalia Syskid (www.SysKid.eu) established robust strategies that detail glycome studies rather than rigorous, systematic therapeutic approach for was thethe treatment ofofto This research supported and the creation of partially high-skilled jobs. by progression. robust strategies that detail the glycome of Martin, willevaluation. utilise cell culture andbyanimal further our understanding of (IBD) chronic scientific This work doctoral inflammatory bowel disease bykidney bringing More than 15,000 people in Ireland HIV-infected patients methodology can be categorised candidate Ravindra Pushker set outand to together the research of the on millions of people worldwide larger are living with set the the basis of the of years it takes for determine in a substantially sample Taylor group withnumber the proprietary symptoms IBD today.

Current therapeutic them to progress to delivery AIDS. Some patients if any association exists between disease liquid/emulsion drug system, options for this chronic debilitating disease are maintain stable CD4 by lymphocyte counts and progression and particular amino acid LEDDS®, developed Sigmoid Pharma. very limited with surgery within often being thegene. only do not go on to develop AIDS even after more differences or deletions the nef Commenting award, Professor Taylor viable option. The Sigmoid product, currently than 10 yearsonofthe infection. cells, tissues and fluids.

Glycomics needs the supporting framework On a per patient basis, there was no excess most likely to die as a result of the raised New research led by Conway Fellow Dr said, “We are delighted for Dr Coulter and his in a phase II clinical study, uniquely enables of of extensive, Scientists arewell-curated curious as todatabases why LTNP patients orsupport more defective glucose levels diabetes.

Breandán indicates that treatment most likely to die asinone athat result of without the raised nef New research ledit by Conway Fellow Drlongteam and Kennedy indeed reflects well onthese ourand Commercial packages HPLC oral delivery ofseen awith powerful drug flexible analytical tools.(LTNP) Currently, this do field term, nonprogressor patients not sequences when compared to progressors. of diabetic blindness should look at partnership.

A key driver of successful glucose levels seen in diabetes.

Breandán Kennedy indicates that treatment results insystemic both academic outputs and the of Irish biopharmaceutical development instruments cannot facilitate the extraction causing side-effects. of study lacks the established, Dr Kennedy and his team found that new blood Research from Conway Dr “We analysed samples follicular develop AIDS. This may reflect differences in While the high frequency ofthe amino acid protecting the neurons responsible colour scientific research incentralised 2010 isFellows, meaningful large quantities of data. toward Inof an effort to alleviate application of research clinical product company, Sigmoid recently of diabetic blindness should look atforscooped comprehensive and Pharma data vessels and the neuronal cell death in diabetic Dr Kennedy and his team found that new blood Lorraine Brennan and Dr Fionnuala fluid surrounding the immature ovum or Under normal conditions, the gastrointestinal the host, viral genetics or environmental replacement at particular residues is indicative this bottleneckwith within high-throughput vision in thethe eye and not just targeting the interaction of academia with industry that development indigenous companies.” the overall Innovation of the Year award at protecting neurons responsible for colour collections, standards and information retinopathy can arise independently of McAuliffe outlines aexist new way to thefor egg before itthewas retrieved for IVF,” says vessels and neuronal cellteam death in each diabetic glycomic projects, the NIBRT have factors potentially be exploited of rapid evolvement, permutation testing blood vessels as is currently the practice. the inaugural Irish Times All-Island vision inthat the could eye and not just targeting reporting protocols that within other.

In addition, they identified cone Commenting on the Taylor Dr measure the potential success rate Dr Brennan.

“There were clear metabolic developed a web-based toolcollaboration, that that interfaces retinopathy can arise independently of each the treatment of disease. showed that residues with more replacements Innovation Awards.

The life-science SME, genomics and proteomics. blood vessels as the is currently the practice. photoreceptor neurons, those involved inTaylor Nearly 2.5 million people worldwide are blind Coulter said, “The collaboration with the with the Waters chromatography software of an embryo before it is transferred differences between the follicular fluids other.

In addition, they identified that cone than expected were not statistically significant. founded by UCD pharmacology graduate, Dr Studies in million model organisms have that colour vision and used inautomate daylight, are most due to into diabetic This secondary package to clearly improve and export Researchers, Drretinopathy.

Natalia Artemenko and laboratory demonstrates thethe potential back the womb during inshown vitro from women who successfully achieved photoreceptor neurons, those involved in Nearly 2.5 people worldwide areDrblind Ivan Coulter, has actively collaborated with of data toby fileglucose formats for subsequent Matthew from the National infectionCampbell with nef-deficient virus shows an The researchers conclude that current data affected the high levels. complication of(IVF). diabetes activates theInstitute growth that can bevarious realised through focused fertilisation pregnancy asand a result ofdaylight, IVF to the colour vision used in arefluids most due to diabetic retinopathy.

This secondary Conway Fellow, Professor Cormac Taylor of Bioprocessing Research & (NIBRT) analysis.

The modular architecture of the tool provides no evidence that individual residues of infection ofattenuated new leaky course blood vessels in Training theand eyesome and is application of basic research.

The development from thebywomen who did not.” affected the high glucose complication of diabetes activates the growth since being granted aProfessor Science Foundation The research team made theirlevels. observations also facilitates the manipulation ofondata from led

by Conway Pauline Rudd responsible for Fellow, the adeath of photoreceptors, of a smart economy will depend like-minded The fluid within woman’s ovaries Ireland industry research partnership award of new leaky blood vessels in theweb-based eye and is using data a novel zebrafish model of diabetes, have developed open access, other management systems. the neurons thatan send visual to our collaborative identifying opportunities Theaccurate researchpartners teamvalidated made theirmethod observations that surrounds the egg ormessages oocyte holds An and of in 2004. responsible the death of photoreceptors, interface thatfor facilitates extraction, querying which resembles the early stages of diabetic brain. and realising basic and applied research The NIBRT team are now working to integrate metabolic information that can improve embryo assessment and selection for using a novel zebrafish model of diabetes, and sharing of HPLC-glycan data generated in the neurons thatby send messages to Meta-analysis UCDvisual researchers led byour studies in humans haveItshown that non retinopathy in humans. is an exciting The Irish Times recognises the stellar GlycoExtractor theearly EUROCarbDB synergies.

Thiswith collaboration, initiated through predictions on award which embryo isShields more transfer might allow implementation of which resembles the stages of hope diabetic high throughput Conway Professor Denis progression was associated with gross development for the group who now to Until now,Fellow, itperformance was processes. unclear if the changes to has brain. innovative of Sigmoid Pharma in framework toin provide a comprehensive higharetinopathy SFI research supplement, highlights the likely to lead to pregnancy. single embryo transfer as the standard humans.

It is an exciting determined that there is no clear evidence deletions in the nef gene. further extend their research and establish vessels and neurons occurred independently of their application of research and development.

Glycosylation is the most common and throughput HPLC data analysis platform fora potential that innovative indigenous companies development for thediabetic group disease. who now hope to Until now,and it was unclear ifviral the changes to is thatother particular defective sequences model of lateand stage one which type of retinal neuron structurally diverse post-translational the storage annotation experimental The company has developed two new drugin working with academia canof realise.”

However, much of the research the area to further their research andin establish a vessels and neurons independently of the HIV-1 nef gene oroccurred certain regions of data.

Theextend integration of next generation modification of proteins.

More than half ofthe allnot technologies, LEDDS™ and SmPill™, which date has been based on observational or case model of late stage diabetic disease. one other and which type of retinal neuron is gene products have been shown to be bioinformatic tools will further the protein play a significant role in disease Taylor’s collaboration with Sigmoid Pharma has only enhance the solubility and permeability of studies rather than rigorous, systematic glycosylated. many specific glycans or development unified approaches for progression. certainly beenofsuccessful by these metrics with the drug but With can deliver it to targeted locations scientificlarge evaluation.

This workdata by doctoral glycoforms showing potential as cancer handling scalepublications glycomics initiatives three co-authored to date in two of in the gastrointestinal tract, including the HIV-infectedthere patients be categorised candidate Ravindra Pushker set out to with applications in biomarker discovery biomarkers, is ancan increasing need toon the highest ranking scientific journals in the colon.

tract is lined with cells that block the contents remodelling of the uterine environment of the gut from leaking into the intestine. In an for implantation; nutrient metabolism; IBD patient, this barrier is broken&and the embryo growth, development contents of the gut leak outof into surrounding protection; maintenance uterine health areas.

The research teammodulation. in UCD Conway used and maternal immune

amodels modelto ofidentify IBD and, by applying a newinclass processes involved earlyof known as hydroxylase inhibitors, were Adrugs Science Foundation Ireland strategic CKD progression and investigate novel models to identify processes involved in early able to almost completely reverse the this research centre (SRC) award funded strategies for preventing and slowing CKD progression investigate novel the symptoms of theand disease. research. progression the disease. studies strategies for of preventing and These slowing the will be integrated clinical and epidemiological “When we applied these new drugs to ourwill IBD progression of with the disease.

These studies studies across theclinical consortium using systems model, the gut was tricked into thinking that it be integrated with and epidemiological Reference was being deprived ofcharacterisation oxygen.

This biology methodologies in order to develop new studies the consortium using systems Mullen, Macross et al.

Proteomic ofactivated histotroph during themethodologies preimplantation phase ofinthe cyclenew into protective pathways, turn prevented diagnostic strategies which and treatment options biology in order toestrous develop cattle.

Journal Proteome Research (2012) 11, 3004-to the death ofofthe cellsand that line the options diagnostic strategies treatment prevent CKD development.

Email 3018 doi/10.1021/pr300144q gastrointestinal tract,” explained Professor prevent CKD development. tara.mcmorrow@ucd.ie forEmail details of a PhD Taylor. pre-clinical trial data can tara.mcmorrow@ucd.ie for details of a now PhD position“Our currently available. inform the next phase Sigmoid Pharma product position currently available. development pipeline”.

In addition to the product that is currently in GlycoExtractor advances advances glycan glycan data data manipulation manipulation phase II clinical studies, Sigmoid Pharma is GlycoExtractor developing a LEDDS™-enabled formulation of the hydroxylase inhibitor Conway collaborator scoops Irishto Times Innovation Award dimethyloxaloylglycine (DMOG) to bring design about EUROCarbDB, a research infrastructure Nature Communications; from bovines brains EUROCarbDB, a research infrastructure design

Success in EU FP7 call

effective, safe by andthe targeted of this study funded EU 6thdelivery Framework study funded by the EU 6th Framework potential therapeutic agent.

Programme.

Prospective users can access the Programme.

Prospective users can access the oedema is with the hallmark pathology. tract is lined cells the contents GlycoExtractor tool onthat block GlycoExtractor tool on ofReference the gut from leaking into the intestine. In an http://glycobase.nibrt.ie:8080/DemoGlycoExtra http://glycobase.nibrt.ie:8080/DemoGlycoExtra IBD patient, this barrier is broken and the Claridge, J et al.

Fasciola hepatica is associated with ctor/mainPage. ctor/mainPage. contents gutbovine leak tuberculosis out into surrounding the failureof to the detect in dairy cattle.

Reference Reference NatureThe Communications 22 May 10.1038/ areas. research team in 2012 UCDdoi: Conway web-based interface for high used GlycoExtractor: AAweb-based interface for high GlycoExtractor: ncomms1840 athroughput model ofprocessing IBD and,ofof by applying data adata new class of processing HPLC-Glycan throughput HPLC-Glycan drugs known as hydroxylase inhibitors, were NataliaV. V.Artemenko, Artemenko, MatthewP.P.Campbell, Campbell, andPauline Pauline Matthew and Natalia Campbell, M et al. suppression of claudin-5 M.Rudd Rudd Journal ofTargeted Proteome Research, 2010, (4),pppp M. Journal of Proteome Research, 9 9(4), able to almost completely reverse2010, the decreases and improves cognitive 2037–2041cerebral 2037–2041 symptoms of theoedema disease. outcome following traumatic brain injury. Nature

Communications 22 May 2012 doi:drugs 10.1038/ncomms1852 “When we applied these new to our IBD model, the gut was tricked into thinking that it was being deprived of oxygen. This activated protective pathways, which in turn prevented the death of the cells that line the models to identify processes involved in early gastrointestinal tract,” explained Professor CKD progression and investigate Taylor.

“Our pre-clinical trial data novel can now strategies preventing and slowing theproduct inform thefor next phase Sigmoid Pharma of HIV nef of are critical in determining the will rate progression the disease.

These studies development pipeline”. beofintegrated with clinical and epidemiological disease progression.

Professor Denis studies across theproduct consortium systems InShields addition to the that using isfor currently in of believes that searches modifiers biology inSigmoid order develop phase IImethodologies clinical studies, Pharma isnew progression rates should now to focus on other diagnostic and“Systematic treatment options to developing a LEDDS™-enabled formulation of host and strategies viral factors. evaluation NIBRT Dr Matthew Dr Natalia H&E researchers stained showingCampbell aEmail region and of cerebrum prevent CKD section development. the inhibitor NIBRT researchers Dr Matthew Campbell and Dr Natalia of hydroxylase large quantities ofGlycoExtractor data bylevel bioinformatics Artemenko who developed revealing cerebral damage to the of the tara.mcmorrow@ucd.ie for details of a PhD Artemenko whoas developed dimethyloxaloylglycine (DMOG) to UCD bring about can be currently just important in Cloak, refuting hippocampus.

Courtesy ofGlycoExtractor Brian position available. effective, safethat and are targeted delivery this hypotheses current in the of literature, as potential therapeutic unknown agent. patterns”, he said. it is in discovering

Bioinformatic analysis of HIV progression studies

This research was funded through Science Zebrafish gives blindness GlycoExtractor glycaninto datadiabetic manipulation Foundation Ireland and University College Zebrafish model modeladvances gives insights insights into diabetic blindness

collaborator scoops Irish Innovation Award New testConway can better predict successful IVFTimes embryos Dublin.

EUROCarbDB, infrastructure design Commenting ona research the research, Dr Kennedy study funded by 6th Framework Commenting onthe theEU research, Dr Kennedy said, “By establishing a robust model for early Programme. Prospective users can access the tract is“By lined with cells retinopathy, that blockmodel the and late stage diabetic wecontents would said, establishing a robust for early GlycoExtractor tool on Reference: while procedure maintaining a high of thelate gut fromunderstand leaking into theprogression intestine.

Inofan hope to better the and stage diabetic retinopathy, we would http://glycobase.nibrt.ie:8080/DemoGlycoExtra Meta-analysis to test the association of HIV-1 nef amino pregnancy rate and minimising multiple IBD patient, this barrier isway broken and the of the and pave the identifying hope to better understand thefor progression aciddisease differences and deletions with disease progression. ctor/mainPage.

pregnancies. contents of the out intofor surrounding Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields. new drug targets forleak itsthe successful treatment”. the disease andgut pave way identifying Reference JournalThe of Virology, Aprteam 2010 p3644-3653 areas. research in UCDforConway used A web-based interface high GlycoExtractor: new drug targets for its successful treatment”. research was funded throughdata throughput ofby HPLC-Glycan aThe model ofprocessing IBD and, applying a Science new class of Natalia V. Artemenko, Matthew P. Campbell, and Pauline Foundation Ireland and the Health Research drugs known hydroxylase inhibitors, Reference The research was funded through Science M. Rudd Journalas of Proteome Research, 2010, 9 were (4), pp Wallace M et al.

An investigation into the relationship Board. able to almost completely reverse the 2037–2041 Foundation Ireland and the Health Research between the metabolic profile of follicular fluid, oocyte symptoms Board. of the disease.

Bioinformatic analysis of HIV progression studies

developmental potential and implantation outcome.

Fertility and 5, 1078-1084.e8 Reference: “When we Sterility applied97;these new drugsMay to 2012 our IBD model, the cone gut was tricked into thinking Predominant photoreceptor dysfunction in athat it of HIV nef are critical in determining the rate Reference: hyperglycaemic model ofofnon-proliferative was being deprived oxygen. Thisdiabetic activated of diseaseYolanda progression.

Professor Denis Predominant cone photoreceptor in a retinopathy.

Alvarez, Jenneth Chen,prevented Alison protective pathways, which indysfunction turn Shields believes that searches for modifiers hyperglycaemic model non-proliferative Reynolds, Waghorne, Johnline J. O’Connor, Breandanof the deathNore of the cellsofthat the diabetic progression rates should now focus on other retinopathy.

Yolanda Alvarez, Jenneth Chen, Alison Kennedy.

Disease Models & Mechanisms (2010) gastrointestinal tract,” explained Professor Reynolds, John J. O’Connor, Breandan host and Nore viralWaghorne, factors. “Systematic evaluation Taylor.

“Our pre-clinical trial data can now Kennedy.

Models & Mechanisms (2010) of large Disease quantities of data by bioinformatics inform the next phase Sigmoid Pharma product can be just as important in refuting development pipeline”. hypotheses that are current in the literature, as is in discovering unknown heinsaid.

Init addition to the product thatpatterns”, is currently