Conway Focus Issue 11 Sept 2010

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collaborator scoops Irish chemotherapy Times Innovation Award PredictingConway patient responses to ovarian cancer

Centre of Excellence hosts international workshop these cells also display a compromised work, Dr McCann said “Up to 30% of

Irish biopharmaceutical development Late diagnosis, recurrence and company, Sigmoid Pharma recently scooped chemoresistance all contribute to the overall Innovation of the Year award at the high morbidity and mortality in the inaugural Irish Times All-Island As a European Centre of Excellence, the ovarian cancer patients.

Currently, Innovation Awards.

The life-science SME, Department of Rheumatology St Vincent’s there is by noUCD way to identify in those founded pharmacology graduate, Dr Ivan Coulter, has actively collaborated with women who will benefit most from University Hospital was chosen to host an Conway Professor the firstFellow, linetwo-day therapy ofCormac choice, a international workshop onTaylor March since being granted a Science Foundation paclitaxel-based chemotherapy.

26th & 27th 2010.

Sponsored

by Roche Ireland industry research partnership award

Pharma, in 2004. the Participate workshop gave

May

Research led byaward Conway Fellow, Dr.stellar twenty from centres in The Irishrheumatologists Times recognises the innovative performance ofand Sigmoid Pharma Amanda McCann PhD collaborators Europe and Australia the opportunity to in their of research in St.application James’, Holles Streetand anddevelopment.

Beaumont witness the care of patients with rheumatoid The company has developed two new Hospitals in Dublin has focused ondrug arthritis (RA) at St Vincent’s. technologies, LEDDS™ and SmPill™, which not the deficiency protein 2 13:12 2010.qxd:Layout 1thecopy 07/05/2010 onlymitotic enhancearrest solubility and permeability of (MAD2).

Their published the drug but can recent deliver itfindings to targeted locations the gastrointestinal tract, including the in Cell Cycle gives further insight into colon.this protein is regulated and how brings scientists closer to collaboration identifying is The Sigmoid Pharma-Taylor facilitating the role development a new its potential in a cell’sofresponse to therapeutic approach for the treatment of paclitaxel.

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

This study investigated how MAD2 is

The Participate programme focused on Dr Commenting the Taylor collaboration, regulated inon ovarian cancer focusing on Coulter said, “The collaboration with advanced treatment regimens for RAthe in Taylor the the methylation status of the MAD2 laboratory clearly practical demonstrates theofpotential clinic, including biologic promoter and thethrough effectaspects on MAD2 that can be realised focused infusion therapy carried out in the accredited levels of tumour common application of basichypoxia; research. aThe development suite that economy provides optimal care on forlike-minded RA tumour of a smartmicroenvironment will dependreflecting patients.

In addition to lectures from Conway collaborative partners identifying opportunities deprived oxygen levels that is integral to Fellows, Professors Oliver FitzGerald and and realising basic and applied research chemoresistance. synergies.

This collaboration, initiated through Douglas Veale, delegates heard from clinical anurse SFI research supplement, highlights the specialists about patient education, Commenting on the work, postdoctoral potential that innovative indigenous companies screening and monitoring of biological researcher Maria Prencipe PhD said, working withDr academia can realise.” therapies.

“We found methylation of Page 3 that aberrant Taylor’s collaboration with Sigmoid Pharma has the promoter region was certainly been successful by not theseinvolved metrics with in regulating MAD2 expression.

Using three co-authored publications to date in two of the highest ranking in the CAIX, a marker ofscientific hypoxia,journals we found less field, Gastroenterology and Proceeding of the MAD2 protein expressed under hypoxic National Academy of Sciences, as well as the conditions. We also demonstrated that generation of proprietary innovative products down-regulation of MAD2 isjobs. associated and the creation of high-skilled with up-regulation of p21 in hypoxia, More than 15,000 people in Ireland and suggesting a role for p21 into regulating variety of in order millions of solutions people worldwide areunderstand living with the the MAD2 expression”. structural basistoday. for the difference in biological symptoms IBD Current therapeutic

tract is lined with cells that block the contents ofpatients the gut from into theto intestine.

In an mayleaking not respond the current IBD patient, this barrier is broken and the standard chemotherapy (paclitaxel contents of the gut leak out into surrounding Addressing combination). the international In guests, Ms Mary /platinum order to used areas.

The research team in UCD Conway Duff, of Nursing and it Ms. Kayclass of outcome, crucial aimprove modelDirector of patient IBD and, by applying aisnew Connolly, Assistant Director of Nursing for the drugs known as hydroxylase inhibitors, were that we establish what factors influence able to & almost reverse the Bone Joint completely Unit expressed hope that an individual’s response to their chemotherapy symptoms of theof disease. the experience the multidisciplinary team

and which factors explain why some

from St wouldnew provide a to template “When weVincent’s applied these drugs our IBDfor patients fail to benefit from standard model, the gut was tricked into thinking it delegates to reproduce similar care andthat first-line chemotherapy while others get was being deprived of oxygen. This activated facilities forremission”. the management of RA patients in long-term protective pathways, which in turn prevented their respective countries. the death of the cells that line the This work wastract,” supported

by Professor IRCSET, Irish gastrointestinal explained Taylor.

“Our pre-clinical trialEccles data can now Cancer Society and the Breast inform theResearch next phase Sigmoid Pharma product Health Fund as well as internal development pipeline”.

UCD funding.

In addition to the product that is currently in phase II clinical studies, Sigmoid Pharma is Reference: a LEDDS™-enabled formulation of developing MAD2 down-regulation in hypoxia is independent of the hydroxylase inhibitor promoter hypermethylation. Maria Prencipe, Aloysius dimethyloxaloylglycine (DMOG) to bring about McGoldrick, Antoinette S Perry, Anthony O’Grady, effective, safe and targeted delivery of this Sine Phelan, Barbara McGrogan, Patricia Fitzpatrick, potential therapeutic agent.

Jenny A Watson, Fiona Furlong, Donal J Brennan, Mark Lawler, Elaine Kay and Amanda McCann. Cell Cycle Volume 9, Issue 14 Pages 2928 - 2937 July 15, 2010

Frog peptide structure selected for journal cover

inflammatory bowel disease (IBD) by bringing

together thehave research methodology ofthat the The team An image of with the previously frog peptideshown structure central Taylor group the proprietary lowered levels of MAD2 induce cellular to the work of adrug UCD Conway research team liquid/emulsion delivery system, senescence, where cells are viable but was selected as the by front cover image for the LEDDS®, developed Sigmoid Pharma. not dividing.

Aprilactively 2010 edition of theImportantly, scientific journal, Commenting on the award, Professor Taylor Biochimica Biophysica (BBA);and his said, “We areetdelighted for Acta Dr Coulter Proteins Proteomics. team and & indeed it reflects well on our partnership. A key driver of successful Peptides research in the skin many species of frog scientific in of 2010 is meaningful have anti-bacterial and anti-fungal properties interaction of academia with industry that

options activity.for this chronic debilitating disease are very limited the withfuture surgerydirection often being Regarding of the thisonly viable option. The Sigmoid product, currently This particular XT-7 peptide, isolated from the inskin a phase II clinical study, uniquely enables for of Silurana tropicalis, shows potential oral delivery of a powerful drug without drug development as it has impressive activity causing systemic side-effects.

Conway collaborator scoops Irish Times Innovation Award UCD clinician scientist wins prestigious award

against the growth of bacteria and Candida Under normal conditions, the gastrointestinal albicans. However, this potential as an antias well as the ability to lyse or rupture Postdoctoral research fellow, Dr Donal Womens andacademic Infants University Hospital, results in both outputs the Irish biopharmaceutical development infective agent is restricted by itsand haemolytic May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3 mammalian cells.

This innate immunity application of research toward product company, Sigmoid Pharma scooped Brennan became the first recently Irish recipient works research groupclinical of Professor activity.in the protects it from attack.

These properties of development with indigenous thethe overall Innovation of the Year award at of European Young Researcher Award William Gallagher.

He hascompanies.” been using the Irishare Times All-Island froginaugural skin peptides exciting from the A change the amino acid structure of Dr the at the 2010 Euroscience Open Forum the latesttoinon high-throughput protein Commenting the Taylor collaboration, Innovation The life-science SME, prospect ofAwards. being developed into XT-7 peptide can create an analogue that Coulter said, “The collaboration with the Taylor in Turin,by Italy.

The award recognises screening technology to identify and founded UCDvaluable pharmacology graduate, Dr therapeutically anti-infective and antilaboratory clearly demonstrates the retains anti-infective properties butpotential without the outstanding scientists the early with validate new biomarkers of breast Ivan Coulter, has activelyincollaborated cancer agents. that can be realised through focused complicating haemolytic activity.

The single Conway Fellow, Professor Cormac Taylor stages of their career who have already and ovarian cancer as well as trying to application of basic research.

The development Meta-analysis

by UCD researchers led by studies in humans have shown that non since being granted a Science Foundation amino acidhow substitution (glycine replaced byin demonstrated excellence atHewage national improve is interpreted Conway Fellow, Dr Chandralal andand his of a smart economy willdata depend on like-minded Conway Fellow, Professor Denis Shields has progression wasassay associated with gross Ireland industry research partnership award lysine) improves thegene. therapeutic potential of team carried out there molecular of the European levels. clinical laboratories. collaborative partners identifying opportunities determined that is nomodelling clear evidence deletions in the nef in 2004. and and applied research that defective viral sequences in a XT-7particular peptide and its analogue [G4K]XT-7 in thisrealising naturallybasic occurring peptide.

tract is lined with cells that block the contents of the gut from leaking into the intestine. In an IBD patient, this barrier is broken and the contents of the gut leak out into surrounding areas. The research team in UCD Conway used a model of IBD and, by applying a new class of drugs known as hydroxylase inhibitors, were able to almost completely reverse the of HIV nef of arethe critical in determining the rate symptoms disease. of disease progression. Professor Denis “When we applied these new drugs to our IBD Shields believes searches for modifiers of Cover of April 2010that edition of Biochimica et Biophysica model, the gut wasshould into focus thinking it progression rates now on that other Acta (BBA); Proteins &tricked Proteomics. was deprived of oxygen.

This evaluation activated hostbeing and viral factors.

“Systematic Dr Donal pictured at ESOF 2010prevented in Turin, Italy protective pathways, in bioinformatics turn of large Brennan quantities ofwhich data by the of as theimportant cells that in line the candeath be just refuting gastrointestinal explained Professor hypotheses thattract,” are current in the literature, as Taylor. pre-clinical trial data can now it is in“Our discovering unknown patterns”, he said. inform the next phase Sigmoid Pharma product This researchpipeline”. was funded through Science development Foundation Ireland and University College InDublin. addition to the product that is currently in phase clinical Sigmoid Pharma is tract isIIlined withstudies, cells that the contents (thomas.scharzl@ucd.ie ) block and postdoctoral developing a LEDDS™-enabled of the gut from leaking into the formulation intestine. In of an researchers, Drinhibitor David Gomez the IBD hydroxylase patient, this barrier is broken and the (david.gomez@ucd.ie) and Dr Craig Slattery dimethyloxaloylglycine (DMOG) to bring about contents Reference:of the gut leak out into surrounding effective, targeted of nef thisamino (craig.slattery@ucd.ie ) invite for Meta-analysis to and test the association ofsuggestions HIV-1 areas.

Thesafe research team indelivery UCD Conway used potential therapeutic agent. acid differences and deletions with disease progression. forum schedule. a the model of IBD and, by applying a new class of

Bioinformatic analysis of HIV progression studies

The Irish Times award recognises the stellar

the Brennan, HIV-1 nef agene or certain regions Dr specialist registrar inof thein innovative performance of role Sigmoid Pharma protein play a significant in disease obstetrics & gynaecology at the Coombe their application of research and development. progression.

The company has developed two new drug HIV-infected can beSmPill™, categorised on not technologies,patients LEDDS™ and which the basis of the of years it takes for of only enhance thenumber solubility and permeability them to progress to AIDS. Some patients the drug but can deliver it to targeted locations maintain stable CD4 lymphocyte counts in the gastrointestinal tract, including theand do not go on to develop AIDS even after more colon. than 10 years of infection.development Irish biopharmaceutical A new fortnightly forum for Conway graduate The Sigmoid Pharma-Taylor collaboration isand Doctoral students Adriana Michielsen company, are Sigmoid Pharma recently scooped Scientists as to winners why longfacilitating the curious development of a these new and postdoctoral researchers will be at launched Edwina Cahill were joint the the overall Innovation ofthe thetreatment Year award term, nonprogressor (LTNP) patients do not therapeutic approach for of at in May 2010.

This initiative will give early6th annual UCD Conway Postgraduate the inaugural Irish All-Island develop AIDS.bowel This Times may reflect differences in inflammatory disease (IBD) bringing th by stage researchers the opportunity to talk about Symposium held on June 18 2010.

Innovation Awards.

The the host, the viral genetics orlife-science environmental together research methodology of SME, the sciencegroup and issues that concern them in an founded by UCD pharmacology graduate, Dr Adriana works the colorectal research factors that could potentially be exploited for Taylor within the proprietary Ivan Coulter, has actively informal environment withcollaborated refreshments the treatment of the disease. liquid/emulsion drug delivery system, group under the supervision of Dr. with Conway Professor Cormac Taylor provided!Fellow, Content forby the forum will be LEDDS®, developed Sigmoid Pharma.

Jacintha in the Education Studies inO’Sullivan model organisms have shown & that since being granted a Science Foundation Research Centre, Staward, Vincent’s University infectionindustry with nef-deficient virus shows an Commenting on the Professor Taylor Ireland research partnership award attenuated course of infection and said, “We are delighted for Dr Coulter and his Hospital.

Her presentation wassome entitled in 2004. team and indeed it reflects well on the ourstellar “The effect of tumour microenvironment The Irish Times award recognises partnership.

A key driverofofSigmoid successful innovative performance Pharma in scientific research 2010 isand meaningful their application of in research development. interaction of academia with industry The company has developed two new that drug

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

This collaboration, initiated through been supplement, based on observational or case adate SFI has research highlights the studies rather than rigorous, systematic potential that innovative indigenous companies scientificwith evaluation.

This by doctoral working academia canwork realise.” candidate Ravindra Pushker set out to Taylor’s collaboration with Sigmoid Pharmaset has determine in a substantially larger sample certainly been successful by thesedisease metrics with if any association exists between three co-authored publications to date progression and particular amino acid in two of the highest ranking scientific journals the differences or deletions within the nefingene. field, Gastroenterology and Proceeding of the results in by both academic outputs and the On a per patient basis, there was no excess decided the members but it is envisaged components on dendritic cell function National Academy of Sciences, as well product as theof application of research toward clinical LTNP with aone or defective nef that itpatients will of include mix ofmore technology generation proprietary innovative products in colorectal cancer”.

Edwina presented development with compared indigenoustocompanies.” sequences when progressors. overviews, informal and formalAutocrine research and the creation ofthe high-skilled jobs. her research on “Novel While the high ofcollaboration, amino acid Dr Commenting onfrequency the Taylor seminars, PhD viva rehearsals and and career Function of the BMP Antagonist More than 15,000 people in Ireland replacement at particular residues isGremlin: indicative Coulter said, “The collaboration with the Taylor development talks from within and beyond millions of people worldwide are living with the a Key Role in Hypoxic Pulmonary of rapid evolvement, permutation testing laboratory clearly demonstrates the potential academia.

Forum committee members, PhDof symptoms IBD today.

Current therapeutic showed thatrealised residues with more replacements Hypertension”.

She works in the group that can be through focused student MrPaul Thomas Schwarzl options for this chronic debilitating disease are than expected were not statistically significant. application of basic research.

The development Professor McLoughlin. very limitedeconomy with surgery often being the only of a smart will depend on like-minded The researchers conclude that current data viable option.partners The Sigmoid product, currently collaborative identifying opportunities provides no that individual residues in a phase II evidence clinical study, uniquely enables and realising basic and applied research oral delivery of a powerful drug without synergies. This collaboration, initiated through causing systemic side-effects. a SFI research supplement, highlights the

ofConway Conwaycollaborator postdoctoral &Symposium graduate forumInnovation Award th scoops Irish Times 6Launch annual Conway Postgraduate

technologies, LEDDS™ and SmPill™, which not only enhance the solubility and permeability of the drug but can deliver it to targeted locations in the gastrointestinal tract, including the colon.

potential that innovative companies Under normal conditions,indigenous the gastrointestinal working with academia can realise.”

Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields.

drugs as hydroxylase inhibitors, were Journalknown of Virology, Apr 2010 p3644-3653 able to almost completely reverse the symptoms of the disease.

“When we applied these new drugs to our IBD model, gut was tricked into thinking that it Adrianathe Michielsen (left) and Edwina Cahill pictured was deprived of oxygen.

This activated withbeing Professor Walter Kolch, Director, UCD Conway protective Institute pathways, which in turn prevented the death of the cells that line the gastrointestinal tract,” explained Professor Taylor. “Our pre-clinical trial data can now inform the next phase Sigmoid Pharma product development pipeline”.

Taylor’s collaboration with Sigmoid Pharma has certainly been successful by these metrics with three co-authored publications to date in two of In addition to the product that is currently in the highest ranking scientific journals in the phase II clinical studies, Sigmoid Pharma is field, Gastroenterology and Proceeding of the developing a LEDDS™-enabled formulation of National Academy of Sciences, as well as the Elaine Quinn the hydroxylase inhibitor generation of proprietary innovative products Communications & Education Officer of HIV nef are critical in determining theabout rate studies in humans have shown jobs. that non dimethyloxaloylglycine (DMOG) to bring and the creation of high-skilled UCD Conway Institute of Biomolecular &Professor Biomedical Research of disease progression.

Denis progression was associated with gross effective, safe and targeted delivery of this More than 15,000 people in Ireland and University College Dublin Shields believes thatagent. searches for modifiers of deletions in the nef gene. potential therapeutic millions of people worldwide are living with the progression rates should nowBelfield, focus onDublin other 4 However, much of theCurrent research in the area to symptoms IBD today. therapeutic Ireland host and viral factors. “Systematic evaluation date hasfor been ondebilitating observational or case options thisbased chronic disease are of large quantities of data by bioinformatics studies rather than rigorous, systematic very limited with surgery often being the only can be just as importantE:inelaine.quinn@ucd.ie refuting scientific evaluation.

This work by doctoral viable option.

The Sigmoid product, currently T: in (+353-1) 716 6706 hypotheses that are current the literature, as candidate set out enables to in a phase Ravindra II clinical Pushker study, uniquely it is in discovering unknown patterns”,716 he said.

F: (+353-1) 6701 determine a substantially larger sample set oral deliveryinof a powerful drug without W:through www.ucd.ie/conway if any association exists between disease This research was funded Science causing systemic side-effects. progression and particular amino acid Foundation Ireland and University College Under normal conditions, the gastrointestinal differences or deletions within the nef gene.

Dublin.

Bioinformatic analysis of HIV progression studies

The Sigmoid Pharma-Taylor collaboration is facilitating the development of a new therapeutic approach forresearchers the treatment Meta-analysis

by UCD ledofby inflammatory bowel diseaseDenis (IBD) Shields by bringing Conway Fellow, Professor has together the that research of the determined theremethodology is no clear evidence Taylor group with the proprietary that particular defective viral sequences in liquid/emulsion drugordelivery the HIV-1 nef gene certainsystem, regions of the Investing in Your Future LEDDS®, developed

by Sigmoid protein play a significant role inPharma. disease progression. on the award, Professor Taylor Commenting

said, “We arepatients delighted forbeDrcategorised Coulter andonhis HIV-infected can team and of indeed it reflects the basis the number of well yearsonit our takes for partnership.

A keyto driver successful them to progress AIDS.ofSome patients scientific research in 2010 is meaningful maintain stable CD4 lymphocyte counts and interaction of to academia thatmore do not go on developwith AIDSindustry even after than 10 years of infection.

Scientists are curious as to why these long-

On a per patient basis, there was no excess of LTNP patients with one or more defective nef

September 2010 Issue May 2010 Issue 101 11 september 2007 Issue

May 2010.qxd:Layout 1 copy

Success in EU FP7 call disease (CKD) and improve patient treatment, Conway researchers led by Dr. Tara McMorrow and Professor Michael Ryan have with particular focus on CKD arising from May 2010.qxd:Layout 1 copy 07/05/2010 13:12 3 diabetes and Page 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 from 15 countries and the project is due to run Disease Diagnosis and Treatment (SysKid) for five years. consortium under the European Union FP7 programme.

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

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

GlycoExtractor advances glycan data manipulation Conway collaborator scoops Irish Times Systems model of signalling control Worm research reveals cilia disease geneInnovation functionAward

Glycomics needs the supporting framework cells, tissues and fluids.

EUROCarbDB, a research infrastructure design study funded by the EU 6th Framework of extensive, well-curated databases and Commercial packages that support HPLC flexible analytical tools. Currently, this field Programme. Prospective users can access the instruments cannot facilitate the extraction of of study lacks the established, GlycoExtractor tool on large quantities of data.

In an effort to alleviate http://glycobase.nibrt.ie:8080/DemoGlycoExtra comprehensive and centralised data this bottleneck within high-throughput tract lined with cells thatit block the function contents results in both academic outputs and the Irish biopharmaceutical development Fail-safe switches have been used in to turn on and off biological decisions.Dr noisyissignals, meaning can still collections, standards and information ctor/mainPage.

Research by Conway Fellow, Dr Oliver the function of worm Arl13b causes the complex traits including obesity, diabetes, glycomic projects, the NIBRT team have of the gut despite from leaking into the intestine. application of research toward clinical product company, Sigmoid Pharma recently scooped mechanics andwithin electronics for years to Marc Birtwistle (SBI), one of the researchproperly major alterations to In itsan reporting protocols that exist Blacque has revealed ciliary membrane to bulge and become ReferenceIBD mental retardation andiseven cancer. adevelopment web-based tool indigenous that interfaces patient, this barrier broken and the companies.” the overall Innovation ofnew the Year awarddeveloped at what devices do information under A web-based interface for high genomics and control proteomics. ers involvedwith in this study explains that GlycoExtractor: components and inexact messages. chromatography about a gene implicated in Joubert misshapen as well as software affecting the ability throughput of contents of the gut leak outdata into surrounding the inaugural Irish Times All-Island processing of HPLC-Glycan different circumstances.

They arewith the Waters the Taylor Dr Natalia V. areas. “rather than taking a ‘one piece at awithin time’ Dr Oliver these findings package to Commenting improve andon automate thecollaboration, export Researchers, Dr Natalia and Dr twodisorders Artemenko, Matthew Campbell, and Pauline The Blacque researchP.hopes team inthat UCD Conway used Innovation Awards.

The life-science SME, syndrome and cerebellar other proteins to collaboration properly distribute based onArtemenko the related premise that codes Coulter said, “The with the Taylor M. Rudd Journal of Proteome Research, 2010, 9 (4), approach to understanding how these Commenting on the significance ofppclass the of will ultimately lead to a greater Matthew Campbell frombycharacterised the National Institute ofbone data to various file membrane. formats for subsequent a model of IBD and, by applying a new founded UCD pharmacology graduate, Dr (JSRDs), by blindness, the ciliary must be present for a signal to be laboratory clearly demonstrates the potential 2037–2041 The modularsignal architecture of the tool of Bioprocessing Research understanding only of JSRDs, butwere also complex transduction systems work research, Professor Kholodenko said, “We drugs known as not hydroxylase inhibitors, Ivan Coulter, & actively(NIBRT) collaborated analysis. with abnormalities, cystic kidneys, turned ‘on’.has IfTraining only one or neitheralso code that the canmanipulation be realised through led by Conway Conway Fellow, Professor Pauline Cormac Rudd Taylor facilitates of datafocused from able tohave almost completely reverse the as model Fellow, Professor They also to found that a fully functional of closely related ciliopathies such together create biological function, we now a validated mathematical developmental delay and loss of muscle application of basic research.

The development is present, the signal is ‘off’. have developedsince an open other data management systems. symptoms of theand disease. beingaccess, grantedweb-based a Science Foundation Arl13b protein is needed the Meckel Gruber consider the system afor whole.

Central to that represents theBardet-Biedl behaviour ofsyndrome, this of a smart economy willasdepend onnormal like-minded tone and control.

The findings of this interface that facilitates extraction, querying Ireland industry research partnership award functioning of a protein transport system in as well as perhaps more common The NIBRT team are now working to integrate “When we applied these new drugs to our IBD collaborative partners identifying opportunities the systems biology approach is casting cellular signalling system”. funded through aFellow, Science and sharing of research, HPLC-glycan data generated in in 2004.

New research

by Conway Professor GlycoExtractor with EUROCarbDB cilia.

Thisthe intraflagellar transport system phenotypes model, the gutassociated was trickedwith intocilium thinking that it and basic and applied research our realising biological understanding into a mathhigh throughput processes.

Foundation Ireland President ofthe Ireland Boris Kholodenko and collaborators in The Irish Times award recognises stellar framework synergies. to provide a comprehensive highwas being deprived of mental oxygen.

This activated This collaboration, initiated through (IFT) makes contact with the ciliary dysfunction such as retardation and The research was funded through a Science ematical formalism that allows us to use Young Researcher Award (PIYRA) to throughput Oliver innovative performance of Sigmoid Pharma in RIKEN, Japan has shown that evolution Glycosylation is the most common and HPLC data analysis for protective which in turn prevented amembrane.

SFI research supplement, highlights the Based onplatform these results, they obesity. pathways, Foundation Ireland Centre of Science and computers and maths to understand how their application of research and development.

Blacque, were recently published in the the storagepotential and annotation experimental structurally diverse post-translational the death of the cells that line the that innovative indigenous companies has provided a biological version of these proposed a newof working model for Arl13b, disease (CKD) improve patient treatment, models to identify processes involved award in earlyand Conway researchers led byhas Tara The company developed Engineering and Technology theand system ofwith CellDr. Biology. modification ofJournal proteins.

More than half oftwo all new drug data. The integration of works.” next generation gastrointestinal tract,” explained Professor working with academia can realise.”

He notes and “That Arl13b associates with ciliary switches similar fail-safe CKD progression investigate novel McMorrow and Professor Michael Ryan havemechanisms withnot particular focus on CKD arising from membrane where it functions at the ciliary technologies, LEDDS™ and SmPill™, which bioinformatic tools will further the gene products have been shown to be RIKEN. Taylor.

“Our pre-clinical trial data can now membranes and is required for that control cellular reactions within our strategies for preventing and slowing thecilium diabetes and hypertension.

The multiTaylor’s collaboration with Sigmoid Pharma has successfully secured €485,500 in funding as only enhance the solubility and permeability of One of seven genes associated with JSRDs, to regulate important ciliary membrane development of focus unifiedinapproaches for is on glycosylated. With many specific glycans or inform the next phase Sigmoid Pharma Reference The this publication structure/function both studies worms andproduct progression of the disease. in These will certainly successful by these metrics with own cells. findings research disciplinary research consortium has 25 part of an overall award tocan the the drug butThe deliver itof totheir targeted locations Arl13b codes for aSystems protein already known to large properties such as shape, transmembrane handling scalebeen glycomics data initiatives glycoforms showing potential as cancer development pipeline”.

Ligand-specific c-Fosand expression emerges from the understanding how breast cancer cells be integrated with clinical epidemiological mammals demonstrates the remarkable three co-authored publications to date in two of partners (16 universities, 9 industry partners) in the gastrointestinal tract, including the Biology towards Novel Chronic Kidney wereisroles published inand/or Cell. function biomarkers, there an increasing need to with applications biomarker discovery play in the recently formation proteinindistributions and IFT. spatiotemporal control of ErbB network dynamics. studies across the consortium using systems listen toand two In addition to the product that is currently in the highest ranking scientific journals theNIBRT colon.and Treatment evolutionary conservation of how this from 15 countries thedifferent project issignals due tousing runinthis Diseasehigh Diagnosis (SysKid) researchers Dr Campbell and Natalia develop throughput, highly and Nakakuki T, Matthew Birtwistle MR, Saeki Y,Dr Yumoto N, small Ide K, of cilia, which are sensitive hair-like projections biology methodologies in order Sigmoid to develop new is This research was partially supported by phase II clinical studies, Pharma field, Gastroenterology and Proceeding of the ArtemenkoNagashima who developed GlycoExtractor for five years. systems biology approach.

One signal consortium underthat thedetail European Union FP7 Up to only 20 years ago, many believed G-protein functions.” robust strategies the glycome of T, Brusch L, Ogunnaike BA, OkadaThe cells infrom our bodies continually listen The Sigmoid Pharma-Taylor collaboration is extending the surface of the cell. diagnostic strategies LEDDS™-enabled and treatment options to developing formulation National Academy ofto Sciences, as well as the programme.

HatakeyamaaM, Kholodenko BN. Cell, 2010 Mayof causescilia these cells grow, whereas the most to including be redundant cellular facilitating the development of a new team, postdoctoral for signalsthe in precise their local environment and However, molecular detailsThe of UCD Conway prevent CKD development.

Email Reference the hydroxylase inhibitor generation of proprietary innovative products organelles thatthese have fallen victim to other causes cells differentiate.

28;141(5):884-96 therapeutic approach fordoing the treatment ofresearchers Dr. the Craig Slattery and Dr.to Natalia Syskid (www.SysKid.eu) was established toin ciliafor Joubert syndrome for Arl13b functions ciliary tara.mcmorrow@ucd.ie details of aat PhD dimethyloxaloylglycine (DMOG) to bring about creation of high-skilled jobs. then make appropriate decisions proper and what exactly Arl13b is have inflammatoryofbowel disease (IBD) by bringing evolution a type of cellular position effective, These activate or inactive membranes andand stabilizes protein transport in Martin, will mammalian utilise signals cell culture and-animal currentlysafe available. further our understanding chronic kidney targeted delivery of this remained unclear. body functionality.

For instance, during More than 15,000 people in Ireland and together the research methodology of the Caenorhabditis elegans.

Cevik S, Hori Y, Kaplan OI, appendix.

Wesignalling now know that thesewhich cellular subsequent potential, potential therapeutic agent. pregnancy and after childbirth, a woman’s millions of people worldwide are living with the Kida K, Toivenon T, Foley-Fisher C, Cottell D, Katada T, Taylor group withstudied the proprietary Blacque’s team the gene in the cilia antennae present or on nearlyhave all ofbeen our cells when perturbed symptoms IBD today.faulty Current therapeutic body releases hormones that make certain Kontani K, Blacque OE. J Cell Biol. 2010 Mar 22; liquid/emulsion drug delivery system, of tiny worms (Caenorhabditis elegans) and serve fundamental roles in many implicated in the progression of disease numerous options for this chronic debilitating are 188(6):953-69 LEDDS®, developed bythe Sigmoid Pharma. breast cells develop to on the research, Dr Kennedy to die asand a result of the raised including Commenting New research while led bycollaborators Conway Fellow Drcapability in the University ofmost likely very motility sensory functions, types of in cancer. limited with surgery often being the only produce milk; a process termed glucose levels seen diabetes.

Breandán Kennedy indicates that treatment said, “By establishing a robust model for early Commenting on theparallel award,experiments Professor Taylor Tokyo conducted in signalling pathways critical to development. viable option.

The Sigmoid product, currently of diabetic blindness should look at for Dr Coulter and his and late stage diabetic retinopathy, we would differentiation. said, “We are delighted a phase IIalso clinical study, uniquely enables cultured human cells. Together, they Dr Kennedyin and his team found that new blood This work solves the puzzle of how EUROCarbDB, protecting the neurons responsible for07/05/2010 colour Glycomics needs the supporting framework cells, tissues and fluids. a research infrastructure design to better understand the progression of team and indeed it reflects well on our vessels It is now that defects May 2010.qxd:Layout 1 copy 13:12 Page 3not oral delivery ofsurprising a powerful drug withoutin hope and the neuronal cell death in diabetic confirmed that Arl13b proteins uses lipid vision in the eye and not just targeting the cells have unique responses to of extensive, well-curated and study funded by pave the EU Framework the disease and the6th way for identifying partnership.

Adatabases key driver processes of successful cilium structure and function aresignals associated causing systemic side-effects.

Such cellular listening are colretinopathy can arise independently of each Commercial packages that support HPLC anchors to associate with the ciliary blood vessels as istools. currently the flexible analytical Currently, thisisfield Programme.

Prospective users can treatment”. access the scientific research in practice.

2010 meaningfulother. In addition, drug targets for its successful even when using theextraction same chemical with an ever expanding range ofofhuman new they identified that cone instrumentsUnder cannot facilitate the lectively called signal transduction, and membrane.

GlycoExtractor toolprocesses on of study lacks the established, normal conditions, the gastrointestinal interaction withblind industry that disease (CKD) and improve patient treatment, models to identify involved in early Conway ledof byacademia Dr. Taraare reactions to generate them.

It reveals how photoreceptor neurons, those involved in Nearly 2.5researchers million people worldwide diseases and syndromes, collectively called large quantities of data.

In an effort to alleviate The research was funded through Science a and major challenge in current biomedical comprehensive centralised data http://glycobase.nibrt.ie:8080/DemoGlycoExtra progression and investigate novel McMorrow andretinopathy.

Professor Michael have with particular focus on CKD arising from colour and used in daylight, are most due to diabetic This secondary cells rely on precise control of both clinical theCKD this bottleneck within high-throughput Much of and the on Ryan the project was carried ciliopathies, which have overlapping Foundation Ireland and the Health Research collections, standards information ctor/mainPage. research isactivates towork understand theaslanguage of vision strategies for preventing and slowing the diabetes and hypertension.

The multisuccessfully of secured €485,500 inthe funding affected by the high glucose levels. complication diabetes growth glycomic projects, the NIBRT team have timing and location of these chemical reout by UCD doctoral candidate, Sebiha features such as polycystic kidneys and Board. reporting protocols that exist within Reference this award listening inthe terms reacprogression of the disease. These studies will disciplinary research consortium has 25 part of leaky an overall Systems of new blood vesselstointhe eye of andthe is chemical developed aactions web-based tool that interfaces to create unique cellular Awith web-based for high GlycoExtractor: genomics and Cevik. proteomics.

SheChronic and her colleagues to research livers, degeneration, bone responses The teamretinal made their observations be integrated clinicalinterface occurring within the cell.went onpartners Graphical depiction ofand the epidemiological complex cellular (16 universities, 9 industry partners) Biology towards Novel Kidney responsible fortions the death of photoreceptors, with the Waters chromatography software throughput processing of HPLC-Glycan data using a novel zebrafish model of diabetes, demonstrate in C. elegans how disrupting abnormalities, hydrocephalus, as well as out of seemingly identical chemical reacArl13b at ciliary membrane studies across the consortium using systems biochemical signalling network human from 15 countries and the project is due to run Disease Diagnosis and Treatment (SysKid) the neurons that send visual messages to Reference: package to improve and automate the export Researchers, Dr Natalia Artemenko and Drour Natalia V. Artemenko, Matthew P. Campbell,within and Pauline which resembles the early stages of diabetic biology inResearch, order to2010, develop new breast epithelial cells involving an intricately tion networks.

M. Rudd methodologies Journal Proteome brain. for five to years. consortium under the Union FP7 director Professor Kholodenko, deputy of Matthew Campbell fromEuropean the National Institute of data various file formats for subsequent Predominant coneofphotoreceptor dysfunction in9a(4), pp retinopathy in humans. It is an exciting 2037–2041 diagnostic strategies options toloops” arranged cascade of treatment “coherent feedforward hyperglycaemic model of and non-proliferative diabetic of Bioprocessing Research & Training (NIBRT) analysis. The modular architecture of the tool programme.

Systems Biology Ireland (SBI), is applying development for the group who now hope to Until now, it was unclear if the changes to The UCD Conway including characterised by the pictured “AND gates”, and prevent CKD development.

Email retinopathy.

Yolanda Alvarez, Jenneth Chen, Alison alsoof facilitates the team, manipulation ofpostdoctoral data from led by ConwayaFellow, Professor Pauline Rudd systems biology approach The researchers also that further extend and establish a the vessels and neurons occurred independently ofthe feedback, characterised lines ending researchers Dr.their Craig Slattery andfound Dr. Natalia Syskid (www.SysKid.eu) was established to to for details of by aBreandan PhD Meta-analysis by UCD researchers ledtask by of HIV nef are critical in determining the rate studies inresearch humans have shown that non tara.mcmorrow@ucd.ie Reynolds,negative Nore Waghorne, John J. O’Connor, have developed an open access, web-based other data management systems. listening system isand incredibly model late stagecell diabetic disease. one other and which of neuron is Shields Kennedy. with Disease Models &T”Mechanisms (2010) understanding the mechanism cells use a “sideways rather than an arrow.Denis Martin, will utilise culture animal currently available. further our understanding ofretinal chronic kidney Conwaytype Fellow, Professor Denis has of of disease progression.

Professor progression was associated withrobust gross to position interface that facilitates extraction, querying The NIBRT team are in now that there is no clear Shields believes that searches for modifiers of deletions theworking nef gene.to integrate and sharing of determined HPLC-glycan data generated in evidence GlycoExtractor with the EUROCarbDB that particular defective viral sequences in progression rates should now focus on other high throughput processes. larger programmes such as the new MSc in We introduced 4 new advanced core Ithe amHIV-1 delighted to welcome you to the However, much of the research in the area to to provide a comprehensive highnef gene or certain regions offramework the host and viral factors. “Systematic evaluation date has been based on case modules onobservational a pilotforbasis or this Conway Focus and look forward to working Imaging commencing in by September 2010. throughput technology HPLC data analysis platform Glycosylation is the most common and role protein play a significant in disease of large quantities of data bioinformatics studies rather systematic the storage academic and annotation of rigorous, experimental structurally diverse post-translational year;than those covering principles progression. can be just as important in refuting with you in the coming months! scientific evaluation.

This work by doctoral data. The integration of next generation modification of proteins. More than half of all that are current in initiatives, the literature, as and practical aspects of imaging and Ihypotheses hopelined that awith number of new HIV-infected patients can be categorisedbioinformatic on candidate Ravindra Pushker set the out totheapplied tract cells that block the contents results in both academic outputs andnecessary Irish biopharmaceutical Welcome! of the fluids.

Institute and securing Ireland and IDA client companies.

We gene products have been shown to bedevelopment tools will further the it is is in adiscovering unknown patterns”, he said. cells, tissues and EUROCarbDB, research infrastructure design Glycomics needs the supporting framework proteomics began in late March and will run the basis of the number of years it takes for determine in a substantially larger sample set As an institute with an increasingly including the early-stage researcher forum of theacknowledge gut from leaking into the intestine. an application research achieving toward product company, Pharma recently scooped glycosylated. manySigmoid specific glycans or development of unified approaches for clinical funding tooffacilitate the also the commitment ofInthe study funded by the EU 6th Framework of extensive, With well-curated databases and until mid-June with a further two modules in them to progress to AIDS. Some patients if any association exists between disease This research was funded through Science IBD patient, in this barrier broken the development withsupport indigenous companies.” the overall Innovation of the Yearand awardhandling at Commercial packages that glycoforms showing potential as large scale glycomics dataHPLC initiatives interdisciplinary research focus described this issue,iscan will not and onlythe Programme.

Prospective users access flexible analytical tools.

Currently, this field The publication ofcancer this issue coincides ambitions of our research projects.

European Commission to research and maintain stable CD4 lymphocyte counts and progression and particular amino acid Foundation Ireland and University College genomics and flow cytometry contents of the gut leak out into surrounding the inaugural Irish Times All-Island instruments cannot facilitate the extractiontaking of place with applications in biomarker discovery biomarkers, there is an increasing need to thof Conway GlycoExtractor tool the on community of study lacks thenot established, expertise specialist technology platforms, strengthen Commenting on the Taylor collaboration, DrNIBRT with preparations to innovation through thein7and EU Framework do go in on to develop AIDS eventhe after more quantities differences thethe nefsummer gene.

Dublin. researchers Dr Matthew Campbell Dr Conway Natalia areas.

The research team UCD used Innovation Awards.

Thecelebrate life-science SME, large of data.orIndeletions an effortwithin to alleviate develop high throughput, highly sensitive and over week-long periods during http://glycobase.nibrt.ie:8080/DemoGlycoExtra comprehensive and centralised data th Coulter said, “The collaboration with the Taylor This research was partially supported by we are placed participate inthis the than 10uniquely years of pharmacology infection.

ArtemenkoaProgramme who developed GlycoExtractor researchers and forge new interdisciplinary 10 anniversary of the to UCD Conway We welcome the recent announcement (FP7) and hope to secure theof model of IBD and, by applying a new class founded

by UCD graduate, Drbottleneck within high-throughput robust strategies that detail the glycome of On a per patient basis, there was nopotential excess ctor/mainPage. of months. collections, standards and information laboratory clearly demonstrates the drugs known hydroxylase inhibitors, were Ivan Coulter, has actively with glycomic projects, the NIBRT team Festival ofare Research &ofInnovation of continued investment in Irish research opportunities within this work with education and training the links but willascelebrate andto heighten Scientists curious as tocollaborated whynext thesewith longLTNP patients with one orhave more defective nef reporting protocols that exist within that can be realised through focused Reference able to almost reverse the Conway Fellow, Professor Cormac Taylor developed aby web-based toolcompared that with interfaces retrospective of outstanding research the Government, the money research groups across Europe. term, nonprogressor (LTNP) patients not sequences when progressors. generation of research scientists.

Thedo newly A web-based interface for high genomics and a proteomics. awareness ofcompletely our research and innovation application basic research. development We hope toof determine fromtoThe this pilot if GlycoExtractor: symptoms disease. data since being granted a Science Foundation with the Waters chromatography software Reference: processingofofthe HPLC-Glycan throughput develop AIDS. This may reflect differences in While the high frequency of amino acid achievements and a showcase of current channelled through the main funding of a smart economy will depend on like-minded launched PhD programme in Bioinformatics successes.

Meta-analysis to test the association of HIV-1 nef amino demand for training from within UCD as well Ireland research partnership award Researchers, Dr Artemenko and Dr package to improve andatautomate the exportis indicative Natalia V. Artemenko, Matthew P. Campbell, and Pauline theNatalia host,industry viral genetics or while environmental replacement particular residues weProteome applied these drugs to our IBD collaborative partners identifying opportunities research projects.

Even pausing to bodies including Science Foundation Ireland Professor Walter Kolchnew acid differences and deletions with disease progression.

M. Rudd “When Journal of Research, 2010, 9 (4), pp and Systems Biology recently 80 in 2004. data to various file formats for subsequent Matthew Campbell from National Institute as from external academic centres and factors thatthe could potentially be attracted exploitedoffor of rapid evolvement, permutation testing Ravindrathe Pushker, Jean-Marc Denis C. Shields. model, gut was trickedJacquē, into thinking that it and realising basic and applied researchin 2037–2041 reflect onTimes the past decade, wefor are firmly (SFI), thethat Programme for Research Director of Bioprocessing & Training (NIBRT) analysis.

The modular architecture ofmore the tool Professor Walter Kolch EU and non-EU applicants to 15 The Irish120 recognises theup stellar theResearch treatment ofaward the disease. showed residues with replacements Journal of Virology, Apr 2010 p3644-3653 industry will dictate stand-alone delivery of was being deprived of oxygen. This activated synergies. This collaboration, initiated through led by Conwayinnovative Fellow, Professor Pauline Rudd direction alsoinfacilitates the manipulation ofstatistically data from Enterprise focused on the future strategic Third Level Institutions (PRTLI), performance of Sigmoid Pharma than expected were not significant. advanced modules or inclusion Director, UCD Conway Institute studentships. protective pathways, which in turn prevented athese supplement, highlights thewithin Commenting on the research, Dr Kennedy most toSFI dieresearch as a result of the raised New research led Conway Fellow Dr have shownother Studies in model that likely data management systems. have developedtheir an by open access, web-based application oforganisms research and development. theestablishing death of theacells thatmodel line thefor early potential that innovative indigenous companies glucose levels seen in diabetes.

Breandánthat Kennedy indicates that treatment said, “By robust infection with nef-deficient virus shows an The researchers conclude that current data interface facilitates extraction, querying The company has developed two new drug explained academia can realise.” residues The NIBRT working team arewith now working toindividual integrate of diabetic should look at and lategastrointestinal stage diabetic tract,” retinopathy, we Professor would provides no evidence that attenuated course ofgenerated infection and and sharingblindness oftechnologies, HPLC-glycan data in some LEDDS™ and SmPill™, which not Dr Kennedy andwith his the team found that new blood Taylor.

“Our pre-clinical trial data can now GlycoExtractor EUROCarbDB protecting the neurons responsible for colour hope to better understand the progression of high throughput processes.

Taylor’s collaboration with Sigmoid Pharma has only enhance the solubility and permeability of andtothe vessels neuronal cell death in diabetic inform the next phase Sigmoid Pharma framework provide a comprehensive highvision in the eye and not just targeting the the disease and pave the way for identifying product certainly been successful by these metrics with thethe drug butcommon can deliver it to targeted locations retinopathy can arise independently of each development pipeline”.

Glycosylation is most and throughput HPLC data analysis platform for blood vessels as is currently the practice. three co-authored publications to date in twonew of drug targets for its successful treatment”. in thepost-translational gastrointestinal tract, including thethe other.

In addition, they identified that cone structurally diverse storage and annotation of experimental In addition to the product that is currently in the highest ranking scientific journals in the colon. photoreceptor neurons, those involved in Nearly 2.5 million people worldwide are blind data. The integration of next generation modification of proteins. More than half of all The research was funded through Science phase II clinical studies, Sigmoid Pharma is field, Gastroenterology and Proceeding of the colour vision and daylight, due toproducts diabetic have retinopathy.

This secondary gene been shown to be collaborationbioinformatic toolsused will in further the are most Foundation Ireland and the Health Research The Sigmoid Pharma-Taylor is

Success in EU FP7 call

Zebrafish model gives insights into diabetic blindness GlycoExtractor advances glycan data manipulation Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Director’s Message

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

Zebrafish model gives insights into diabetic blindness

UCD CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH

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collaborator scoopsinIrish Times PotentialConway key regulator identified battle to Innovation target IBDAward

Conway collaborator scoops Irish Times Innovation Award Conway collaborator scoops Irish Times Innovation Award SFI award for membrane trafficking research

Irish biopharmaceutical development company, Sigmoid Pharma recently scooped Irishoverall biopharmaceutical the Innovation ofdevelopment the Year award at Conway Fellow, Professor Jeremy company, Sigmoid Pharma recently the inaugural Times All-Island Simpson hasIrish been awarded a scooped the overall Innovation the Year award Innovation Awards.

TheofIreland life-science SME,at Science Foundation Principal the inaugural Irish Times All-Island founded

by UCD pharmacology graduate, Investigator programme grant worthDr Innovation Awards.

The life-science SME, Ivan Coulter, has actively with €1.58M to uncover thecollaborated molecular founded Fellow,

by UCD Professor pharmacology graduate, Dr Conway Cormac Taylor machinery involved in transporting Ivan Coulter, has actively collaborated with since being granted a Science Foundation particles safelyProfessor throughCormac the cell, and Conwayindustry Fellow, Taylor Ireland research partnership award exploit thisgranted knowledge as aFoundation possible since being a Science in 2004. drug delivery Ireland industrypathway. research partnership award The Irish Times award recognises the stellar in 2004. innovative performance oftrafficking Sigmoid Pharma in The areaTimes of membrane The Irish award recognises the has stellar their application of research andsince development. innovative performance of Sigmoid Pharma intrigued Professor Simpson doingin The company hasofdeveloped twodevelopment. new drug theirdoctoral application research and his research on protein toxins technologies, LEDDS™ and SmPill™, which The company has developed two new drug not and their passage through cells in the only enhance the solubility permeability of technologies, LEDDS™ and and SmPill™, which not University Warwick. worked in of the butof can it He toand targeted locations onlydrug enhance the deliver solubility permeability the toxin research laboratory led by in gastrointestinal tract, the thethe drug but can deliver it toincluding targeted locations colon.

Professor Lynne Roberts thethegene in the gastrointestinal tract, where including colon. for Ricin, the castor bean protein listed The Sigmoid Pharma-Taylor collaboration is among thethetop 5 deadliestof substances, facilitating development a new The Sigmoid Pharma-Taylor collaboration is was cloned. facilitating the development a new of therapeutic approach for theoftreatment therapeutic approach for the (IBD) treatment of inflammatory bowel disease by bringing inflammatory bowel disease (IBD)inby together the research methodology ofbringing the The big unanswered question together the research of other the Taylor group with the proprietary relation to Ricin, andmethodology a number of Taylor group with thedelivery proprietary liquid/emulsion drug system, toxins such as drug E. coli 0157 Shiga-like liquid/emulsion delivery system, LEDDS®, developed by Sigmoid Pharma. and Cholera toxin, by is how theyPharma. are so LEDDS®, developed May 2010.qxd:Layout 1 copy Sigmoid 07/05/2010 13:12 effective at entering and Professor killing cells.

Commenting on the award, Taylor Commenting on the award, Professor Taylor said, “We are for Dr Coulter and his According todelighted Jeremy Simpson, if we said, “We are delighted for Dr Coulter and his team and indeed reflects well on our understood howitit pathways team and indeed reflects wellbetween on our partnership.

A key driver ofare successful cellular compartments controlled, partnership.

A key driver of successful scientific research in 2010 is meaningful scientific research in 2010be is used meaningful this information could to help interaction of with industry industry that that interaction of academia academia design drugs that canwith be better targeted

to various sub-compartments of the cell.

As part of this research project, Simpson will initially add fluorescent labels to non-toxic subunits of Ricin, Shiga and

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

Shiga-like toxins that are known applicationinoftrafficking. research toward clinical product involved On a genomeCommenting with on the Taylor collaboration, development indigenous companies.”Dr wide scale, willcollaboration then down-regulate Coulter said,he “The with the Taylor Commenting the Taylor collaboration, Dron each geneclearly toonsee how this willthe impact laboratory demonstrates potential Coulter “The collaboration with Taylor that canasaid, be realised through focused where toxin travels to within thethecell. laboratory demonstrates thedevelopment potential applicationclearly of basic research. The that can beeconomy realised through focused of a smart will depend on like-minded This systematic exercise should provide a application ofpartners basic research.

The opportunities development collaborative identifying list of candidate genes involved in getting of a smart economy will depend on like-minded and realising basic and applied research via toxins to thepartners endoplasmic reticulum collaborative identifying opportunities synergies. pathway This collaboration, initiated through the rather than being and Golgi realising basic and applied research a SFI research supplement, highlights the destroyed in the lysosomalinitiated pathway. synergies. This collaboration, through that innovative indigenous companies Using bioinformatic and proteomic tools, apotential SFI research supplement, highlights the working with academia can realise.” potential innovative indigenous companies the teamthat should be able to drill down working with academia canSigmoid realise.” and understand the with molecules involved Taylor’s collaboration Pharma has

in morecollaboration detail and potentially the certainly been successful thesereveal metrics with Taylor’s withby Sigmoid Pharma has master regulators of the process. three co-authored publications to date in of certainly been successful by these metricstwo with the highest rankingpublications scientific journals three co-authored to date in in the two of

In collaboration Professor Kenneth field, Gastroenterology and Proceeding the highest rankingwith scientific journals inof thethe National Academy of hope Sciences, asable well to as Dawson, the team be field, Gastroenterology and to Proceeding of the National of Sciences, as well as the generation of proprietary products use this Academy information to innovative functionalise generation of proprietary innovative products and the creation of high-skilled jobs. nanoparticles, move them into the Golgi and the creation of high-skilled pathway and provide a noveljobs. model for More than 15,000 people in Ireland and drug delivery.

More than in Ireland andwith the millions of 15,000 people people worldwide are living millions of people worldwide living with the symptoms IBD today.

Currentare therapeutic

Commenting theCurrent award, Jeremy symptoms today. therapeutic options for IBD thison chronic debilitating disease are Simpson said, “While the technological options for this chronic debilitating disease are very limited Page 3 with surgery often being the only very with surgery often the only challenges this project arebeing enormous, viablelimited option.in The Sigmoid product, currently viable option.

The Sigmoid currently the benefits of product, improved drug in a potential phase II clinical study, uniquely enables in a phase clinical study, uniquely enables design andII delivery far outweigh them”. oral delivery of a powerful drug without oral delivery of a powerful drug without causing systemic side-effects. causing systemic side-effects.

UCD College of Life Sciences have Under normal conditions, the gastrointestinal recognised potentialthe benefits of the Under normalthe conditions, gastrointestinal

tract is lined with cells that block the contents of the gut from leaking into the intestine. In an tract is linedfacility withbarrier cells block IBD patient, this is broken andcontents the screening to that meet notthe only the of the gut leaking the intestine. contents the research gut leakinto out into surrounding needs ofoffrom this but also thoseInofan IBD patient, this barrier is in broken and the used areas.

The research team UCD Conway UCD researchers campus-wide. contents of IBD the gut out into surrounding a model of and,leak by applying a new class of areas.

The research team in UCD Conwaywere used drugs known asScreening hydroxylase inhibitors, The UCD Cell Centre willclass of aable model of IBD completely and, by applying a new to almost reverse the form known part ofasthe suite of Conway drugs hydroxylase inhibitors,core were symptoms of the disease. technologies and will include able to almost completely reverse liquid the handling imaging equipment “When we robotics, applied these new drugs to our IBD symptoms of the disease. and analysis asinto wellthinking as the that it model, the gut software was tricked “When we applied these newcore drugs to our IBD expertise of a dedicated facility was being deprived of oxygen. This activated model, the gut was tricked into thinking that it manager. protective pathways, which in turn prevented was being deprived of oxygen. This activated the death of the cellswhich that line the prevented protective pathways, in turn gastrointestinal explained the death of the tract,” cells that line theProfessor Taylor. “Our pre-clinical trial dataProfessor can now gastrointestinal tract,” explained inform “Our the next phase Sigmoid product Taylor. pre-clinical trial dataPharma can now development pipeline”. inform the next phase Sigmoid Pharma product development pipeline”.

In addition to the product that is currently in phase II clinical Pharma in is In addition to thestudies, productSigmoid that is currently developing a LEDDS™-enabled phase II clinical studies, Sigmoidformulation Pharma is of developing a LEDDS™-enabled formulation of the hydroxylase inhibitor the hydroxylase inhibitor(DMOG) to bring about dimethyloxaloylglycine dimethyloxaloylglycine (DMOG) to bring about effective, safe and targeted delivery of this effective, and targeted potential safe therapeutic agent.delivery of this potential therapeutic agent.

Fluorescently-labelled Shiga-like toxin (red) is trafficked to the endoplasmic reticulum and nuclear envelope (inset), but avoids the degradative endosomal-lysosomal compartments (green)

high throughput imaging technology associated with this project by providing an additional €180K in supporting funding to meet infrastructural and resource requirements. This will allow Professor Simpson to establish a cell

Bioinformatic analysis of HIV progression studies

Meta-analysis by UCD researchers led by Conway Fellow, Professor Denis Shields has determined that there is no clear evidence that particular particular defective defective viral that viral sequences sequences in in the HIV-1 HIV-1 nef nef gene gene or certain regions of the the or certain regions of the Professor Kolch, Director of Irish biopharmaceutical development protein playWalter significant role in protein play aa significant role in disease disease company, Sigmoid Pharma recently scooped Systems Biology Ireland and Conway progression. progression. the overall Innovation of the Year award at Fellow, Professor William Gallagher HIV-infected patients can be categorised on the inaugural Irish Times All-Island will lead two cancer projects HIV-infected patients canresearch be categorised on the basis ofAwards. the number of years takes for Innovation The life-science SME, worth million under theititlatest the basis€18 of the number of years takes for them to progress to AIDS. Somegraduate, patients Dr founded

by UCD pharmacology round the EUto 7th Framework them toof progress AIDS. Some patients maintain stable CD4 lymphocyte counts with and Ivan Coulter, has actively collaborated maintain stablefor CD4 lymphocyte counts and Programme Research (FP7). do not goFellow, on to develop AIDS even after more Conway Professor Cormac Taylor do notbeing go on toofdevelop AIDS even after more than 10 yearsgranted infection. since a Science Foundation than 10 years of infection.

The firstindustry projectresearch led by Professor Kolch Ireland partnership award Scientists are curious as to why these was awarded €12 million by the EUlongto in 2004.

Scientists are curious as to why these longterm, nonprogressor (LTNP) that patients do not explore genetic mutations lead The Irish Times award the stellar term, nonprogressor (LTNP) patients do not develop AIDS. This mayrecognises reflect differences in to the development cancer cells. innovative performance of Sigmoid Pharmainin develop This mayof reflect differences the host,AIDS. viral genetics or environmental This project will use aorsystems biology their application ofpotentially research and development. the host, viral genetics environmental factors that could be exploited for approach focus on understanding The company hasthe developed two new drugfor factors thatto could potentially be exploited the treatment of disease. childhood cancers. technologies, LEDDS™ and SmPill™, which not the treatment of the disease.

Studies in model have shown thatof only enhance the organisms solubility and permeability infection with nef-deficient shows anthat Studies model organisms have shown the druginbut can deliver it tovirus targeted locations attenuated course of infection and some infection with nef-deficient shows in the gastrointestinal tract,virus including thean attenuated course of infection and some colon.

studies in humans have shown shown that that non non progression was associated with with gross gross deletions in the nef gene.

of of HIV HIV nef nef are are critical critical in in determining determining the the rate rate of of disease disease progression. progression. Professor Professor Denis Denis Shields Shields believes believes that that searches searches for for modifiers modifiers of of progression progression rates rates should should now now focus focus on on other other host viral factors.

“Systematic evaluation hostisand and factors.

“Systematic €531K forviral his part ofthat theblock project that tract lined with cells theevaluation contents of large quantities of data by bioinformatics of large quantities of data by bioinformatics will use a systems biology approach toan of the gut from leaking into the intestine.

In can be just as important in refuting canpatient, be just asfunction important in refuting IBD barrier is broken and the inas dissect ciliathis and itsthe disruption hypotheses that are current in literature, hypotheses that current in the as contents of the gutare leak outCilia into surrounding human genetic disease. areliterature, hair-like itit is discovering unknown patterns”, he said. is in inThe discovering unknown patterns”, said. areas. research UCD Conwayheused projections on theteam cell insurface. research through Science aThis model of IBDwas and,funded by applying a new class of This research was funded through Science Foundation and University College drugs knownIreland as hydroxylase inhibitors, were Foundation Ireland and University College Dublin. able to almost completely reverse the Dublin. symptoms of the disease.

Conway success collaborator scoops Irish Times Innovation Award EU FP7 funding for Conway

The Sigmoid Pharma-Taylor collaboration is facilitating the development of a new therapeutic approach for the treatment of inflammatory bowel disease (IBD) by bringing together the research methodology of the

However, However, much much of of the the research research in in the the area area to to date based observational or Professor Gallagher will lead the results in been both academic outputs andsecond the date has has been based on on observational or case case studies than rigorous, application of research towardsystematic clinical product project, awarded million, to look at studies rather rather than€6 rigorous, systematic scientific evaluation.

This by development with indigenous companies.” possible for work difficult-to-treat scientifictreatments evaluation.

This work by doctoral doctoral candidate Ravindra Pushker set out types of breast cancer.

The research candidate Ravindra Pushker set out to to Dr Commenting on the Taylor collaboration, determine in the a substantially larger sample set will explore role of kinases, the determine in“The a substantially larger sample set Coulter said, collaboration with thekey Taylor if any association exists between disease regulators of cell function, in these types if any association exists between disease laboratory clearly demonstrates theacid potential progression and particular amino progression and particular amino acid of breast inthrough order to develop that can becancer realised focused differences or deletions within the nef gene. differencesofortargets deletions within the nef gene. application basic research.

The development therapeutic that may inhibit the Ona asmart peractivation patient basis, there was excess of of economy will depend like-minded rate of of kinases inonno cancer On a per patient basis, there wasdefective no excess LTNP patients with one or more nefof collaborative partners identifying opportunities sufferers.

LTNP patients with oneapplied or more defective nef sequences when compared to progressors. and realising basic and research sequences when compared to progressors.

While theahigh frequency of amino acid synergies.

This collaboration, initiated through Syscilia, collaborative research project While the high frequency of aminoisacid atsupplement, particular residues indicative areplacement SFI research highlights the involving Conway Fellow, Dr Oliver replacement particular residues iscompanies indicative of rapid evolvement, permutation testing potential that at innovative indigenous Blacque, wasresidues awarded €11realise.” million under of rapid with evolvement, testing showed that with replacements working academiapermutation can more this programme. receive showed that residues with morewill replacements than expected wereDr notBlacque statistically significant.

Taylor’s collaboration with Sigmoid Pharma has than expected were not statistically significant.

The researchers concludeby that current datawith certainly been successful these metrics provides no evidence that individual three co-authored publications dateresidues in two of The researchers conclude that to current data the highestnoranking scientific journalsresidues in the provides evidence that individual field, Gastroenterology and Proceeding of the National Academy of Sciences, as well as the generation of proprietary innovative products and the creation of high-skilled jobs.

More than 15,000 people in Ireland and

“When we applied these new drugs to our IBD model, the gut was tricked into thinking that it Reference: was being deprived of oxygen. This activated Reference: to test the association of HIV-1 nef amino Meta-analysis protective pathways, which in turn prevented acid differencestoand with disease progression.

Meta-analysis testdeletions the association of HIV-1 nef amino the of theand cells thatJacquē, line disease theDenisprogression.

Ravindra Pushker, Jean-Marc C. Shields. aciddeath differences deletions with gastrointestinal explained Professor Journal Virology,tract,” Apr 2010 p3644-3653 RavindraofPushker, Jean-Marc Jacquē, Denis C. Shields.

Journal“Our of Virology, Apr 2010 p3644-3653 Taylor. pre-clinical trial data can now inform the next phase Sigmoid Pharma product development pipeline”.

In addition to the product that is currently in phase II clinical studies, Sigmoid Pharma is developing a LEDDS™-enabled formulation of the hydroxylase inhibitor dimethyloxaloylglycine (DMOG) to bring about effective, safe and targeted delivery of this potential therapeutic agent.

The intestinal barrier works byand the results in both academic outputs Irish biopharmaceutical development Research into inflammatory bowel application of aresearch toward clinical product company,(IBD) Sigmoid recently scooped maintaining delicate balance between disease ledPharma

by Conway Fellow, the overall Innovation of the Year at development with indigenous the proliferation and deathcompanies.” of epithelial Professor Cormac Taylor withaward national the inaugural Irish Times All-Island has cells at the surface of thecollaboration, barrier. If the and international collaborators Commenting on the Taylor Dr Innovation Awards. The life-science SME, balances tips“The so that more cells identified a key regulator involved in Coulter said, collaboration withdie thethan Taylor founded by UCD pharmacology graduate, Dr grow, as isclearly the case in IBD, the maintaining the functional integrity of laboratory demonstrates thebarrier potential Ivan Coulter, has actively collaborated with disease (CKD) and improve patient treatment, Conway researchers led

by Dr. Tara is nocan longer intact and cannot function that be realised through focused the gut lining.

The findings, published Conway Fellow, Professor Cormac Taylor properly.

McMorrowinand Professor Michael provide Ryan have with particular focusresearch. on CKD The arising from application of basic development recently Gastroenterology, since being granted a Science Foundation disease (CKD) and improve patient Conway researchers led by Dr.important Tara May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3economy of a smart will depend ontreatment, like-minded diabetes and hypertension.

The multiinformation that may be successfully secured €485,500 in funding as Ireland industry research partnership award McMorrow and Professor Michael Ryan have with particular focus on CKD arising from collaborative partners identifying opportunities This latest research has shown that disciplinary research consortium has 25 part of an overall awardtherapeutic to the Systems in developing a new in 2004. and realising basic applied research diabetes and hypertension.

The multisuccessfully secured €485,500 in funding as in the absence of and an oxygen-sensing partners (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney approach to the treatment of the The Irish Times award recognises the stellar synergies.

This collaboration, initiated through disciplinary research consortium has part of anDiagnosis overall award to the Systems enzyme, prolyl hydroxylase 1 (PHD1), from 15 countries and the project is 25 due to run Disease and of Treatment (SysKid)in disease. innovative performance Sigmoid Pharma a SFI research supplement, highlights the partners (16 universities, 9 industry partners) Biology towards Novel Chronic Kidney epithelial cell death is reduced and the for five years. consortium under European Union FP7 their application of the research and development. potential that innovative from 15 countries theindigenous project is companies due to run Disease Diagnosis and Treatment (SysKid) intestinal barrierand function is enhanced.

The underlying or two environmental programme.

The company hasgenetic developed new drug working with academia can realise.”postdoctoral Thefive UCD Conway team, including for years. consortium under the European Union FP7 Therefore, PHD1 may be a useful target causes of inflammatory disease technologies, LEDDS™ andbowel SmPill™, which not programme. researchers Dr. Craiginhibition Slattery and Dr. Nataliahas Syskid (www.SysKid.eu) established Taylor’s with Sigmoid Pharma for pharmacologic inpostdoctoral IBD. only enhance theunknown. solubilitywas and permeability remain largely However, theto of The UCDcollaboration Conway team, including Martin, will utilise cell culture and animal further our understanding of chronic kidney certainly been successful by these metrics the drug but can deliver it to targeted locations major (www.SysKid.eu) problem associated with this to researchers Dr. Craig Slattery and Dr. Nataliawith Syskid was established threeteam co-authored publications to date inortwo of in the gastrointestinal including the The that by delaying chronic condition is tract, thatofthe lining of the Martin, will propose utilise cell culture and animal further our understanding chronic kidney the highest ranking scientific journals in the colon. suppressing epithelial cell death, the gut becomes leaky, allowing material field,lining Gastroenterology and Proceeding of the gut would be given time to heal from the lumen of the intestine to The Sigmoid Pharma-Taylor collaboration is National Academy of Sciences, as well as the and the integrity of the intestinal barrier pass through this barrier and trigger an facilitating the development of a new generation of proprietary innovative products could be restored. inflammatory response. therapeutic approach for the treatment of and the creation of high-skilled jobs.

Success in EU FP7 call Success in EU FP7 call

tract is lined with block the contents Commenting oncells the that research, Professor of the gut from leaking into thebowel intestine. In an Taylor said “Inflammatory IBD patient, barrier isinbroken andnew the disease is athis condition need of contents of the gut leak out into surrounding and improved therapeutic options.

Our areas.

The research team inthat UCDtargeting Conway used current results indicate the a model of IBD and, by applying a new class of PHD1 enzyme may represent one such drugs known as hydroxylase inhibitors, were models to identify processes involved in early approach.” able to almost completely reverse the CKD progression and investigate novel symptoms of the disease. models toFoundation identify processes inthe early strategies for preventing andinvolved slowing Science Ireland and the CKD progression and investigate novel “When weResearch applied these newThese drugs to our IBD progression of the disease. studies will German Foundation funded this strategies and slowing thethat it model, thefor gutpreventing was clinical tricked into thinking be integrated with and epidemiological research progression of the These studies will was being deprived of oxygen.

This activated studies across thedisease. consortium using systems be integrated with clinical protective pathways, which in epidemiological turn biology methodologies inand order to prevented develop new studies across consortium using options systemsto the death ofstrategies thethe cells that the diagnostic and line treatment Reference biology methodologies inprotects order to develop gastrointestinal tract,” explained Professor Loss of prolyl hydroxylase-1 against colitisnew prevent CKD development.

Email diagnostic strategies andcell treatment options Taylor.

“Our pre-clinical trial data can through reduced epithelial apoptosis and tara.mcmorrow@ucd.ie for details of now a PhDto increasedthe barrier function.

Murtaza M. Tambuwala, prevent CKD development.

Email inform next phase Sigmoid Pharma product position currently available.

Eoin P. Cummins, Colin R. Lenihan, Judithof Kiss, tara.mcmorrow@ucd.ie for details a PhD development pipeline”.

Markus Stauch, Carsten C. Scholz, Peter Fraisl, position currently available.

Felix Lasitschka, Martin Mollenhauer, P. In addition to the product that isSean currently in Saunders, Patrick H.studies, Maxwell,Sigmoid Peter Carmeliet, phase II clinical Pharma is Padraic G. Fallon, Martin Schneider, Cormac T. developing a LEDDS™-enabled formulation of Taylor. Gastroenterology - 02 July 2010 (10.1053/ the hydroxylase inhibitor j.gastro.2010.06.068) dimethyloxaloylglycine (DMOG) to bring about effective, safe and targeted infrastructure delivery of thisdesign EUROCarbDB, a research potential therapeutic agent. study funded by the EU 6th Frameworkdesign EUROCarbDB, a research infrastructure Programme.

Prospective can access the study funded by the EU 6thusers Framework GlycoExtractor tool on users can access the Programme.

Prospective memory formation and suggest that tract is lined with cells http://glycobase.nibrt.ie:8080/DemoGlycoExtra GlycoExtractor tool on that block the contents targeting Aβ dimers alleviate theIn an of the gut from leaking may into the intestine. http://glycobase.nibrt.ie:8080/DemoGlycoExtra ctor/mainPage. memory loss AD. and the IBD patient, thistypical barrier of is broken ctor/mainPage.

Reference contents of theA gut leak out into surrounding web-based interface for high GlycoExtractor: Reference The MRC have awarded Walsh areas.

The processing research team inthe UCDfor Conway used of HPLC-Glycan data throughput GlycoExtractor: A web-based interface high group €550,000 for follow-up research onclass a of athroughput modelV.of IBD and,of by applying a new Natalia Artemenko, Matthew P. Campbell, and Pauline processing HPLC-Glycan data Natalia V. Artemenko, Matthew Campbell, and Pauline larger scale that shouldP.Research, allow for further M. Rudd Journal Proteome 2010, 9were (4), pp drugs known asofhydroxylase inhibitors, M. Rudd Journal Proteome Research, 2010, 9 (4),ofpp 2037–2041 validation ofofcompletely Aβ dimers as mediators able to almost reverse the 2037–2041 disease. Parallel studies (funded by NIH, symptoms of the disease.

GlycoExtractor advances glycan data manipulation GlycoExtractor advances glycan data manipulation inflammatory bowel disease (IBD) by bringing cells, than tissues and fluids.

Glycomics the methodology supporting framework More 15,000 people in Ireland and together theneeds research of the Conway collaborator scoops Irish Times Innovation Award of extensive, well-curated databases andβ-protein millions of people worldwide are living within the Alzheimer’s disease Soluble implicated Glycomics needs the supporting framework cells, tissues and fluids.

Taylor group with theamyloid proprietary

Commercial packages that support HPLC flexible analytical tools.

Currently, symptoms IBD today. Current therapeutic of extensive, well-curated databases andfield liquid/emulsion drug delivery system,this instrumentspackages cannot facilitate the extraction of Commercial support HPLC of study lacks the established, options for this chronicthat debilitating disease are flexible analytical tools.

Currently, this field LEDDS®, developed by Sigmoid Pharma. correlate well with disease status, which large quantities of data.

In an effort to alleviate instruments cannot facilitate the extraction of Alzheimer’s disease (AD) is the most results in both academic outputs and the Irish biopharmaceutical development very limited with surgery often being the only comprehensive centralised data of study lacks theand established, this bottleneck within large quantities of data.

In effort to alleviate raises the question: ifhigh-throughput Aβan causes AD, Commenting onand the Pharma award, Taylor common human dementia and application of The research toward clinical product company, Sigmoid recently scooped viable option.

Sigmoid product, currently comprehensive centralised data confers collections, standards and Professor information this within high-throughput glycomic the NIBRT team have “Weburden are delighted for Dr Year Coulter and at his why doesprojects, the amount ofuniquely Aβcompanies.” in the form development with indigenous the overall Innovation of the award asaid, huge onthat patients, caregivers in a bottleneck phase II clinical study, enables collections, standards and information reporting protocols exist within glycomic projects, the not NIBRT team have team and protocols indeed it reflects well onpathways our of amyloid relate to the developed a plaques web-based tool that interfaces the inaugural Times All-Island and society.

The molecular oral delivery of athe powerful drug without reporting that exist within genomics andIrish proteomics.

Commenting on Taylor collaboration, Dr developed web-based tool that interfaces severity ofa dementia? partnership.

A proteomics. key driver ofwell successful with thesystemic Waters chromatography software Innovation Awards.

The SME, causing side-effects. leading to AD are notlife-science understood, genomics and Coulter said, “The collaboration with the Taylor with the Waters chromatography software scientific research in 2010 is meaningful founded

by UCD pharmacology graduate, Dr package to improve and automate the export Researchers, Dr Natalia and Dr but substantial dataArtemenko indicate that the laboratory clearly demonstrates the potential Under conditions, the gastrointestinal Researchers, Natalia Artemenko andInstitute Drwith package to improve andformats automate the export interaction ofDr academia with industry that Studies recently published infor Brain Ivan Coulter, has actively of datanormal to various file subsequent Matthew Campbell from thecollaborated National amyloid β-protein (Aβ) plays a central May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3 that canto be realised focused Matthew Campbell from the & National Institute of data various filethrough formats for subsequent by the group of Conway Fellow, Conway Fellow, Professor Cormac Taylor of Bioprocessing Research Training (NIBRT) analysis.

The modular architecture of the tool role. application ofmodular basic research.

The development of Bioprocessing Research & Training (NIBRT) analysis.

The architecture the tool Professor Dominic Walsh, looked at from the since granted a Professor Science Foundation led by being Conway Fellow, Pauline Rudd also facilitates the manipulation ofofdata of a facilitates smart economy will biochemically dependofondata like-minded led bydeveloped Conway Fellow, Professor Pauline Rudd also the manipulation from relationship between Ireland industry research partnership award have an open access, web-based other data management systems. collaborative partners opportunities It proposed an that a defect to have developed open access,leading web-based other dataforms management systems. distinct of Aβ identifying and the presence of in is 2004. interface that facilitates extraction, querying and realising basicare and applied research over-production or decreased interface that facilitates extraction, clearance querying The NIBRT team now working to integrate AD-type dementia in 43 brains obtained and of HPLC-glycan data generated The sharing Irish Times award recognises the stellarin The NIBRT team are now working to integrate synergies.

This collaboration, initiated and through causes Aβ of to HPLC-glycan accumulatedata andgenerated ultimately and sharing in GlycoExtractor with the EUROCarbDB from the MRC Cognitive Function innovative of Sigmoid high throughput processes.

GlycoExtractor with the EUROCarbDB aframework SFI research supplement, highlights thehighlead to theperformance cognitive deficits thatPharma in high throughput processes.

Ageing Study. to provide a comprehensive their application of research and development. framework to provide a comprehensive highpotential that innovative indigenous companies characterise AD. The can form Glycosylation thedeveloped mostprotein common and throughput HPLC dataanalysis analysis platform for The company has two new drug Glycosylation isis the most common and throughput HPLC data platform for working with academia can realise.” large insoluble aggregates called amyloid Analysis revealed that the level of SDSthe storage and annotation of experimental structurally diverse post-translational Meta-analysis by UCD researchers led by studies in humans have shown that non technologies, LEDDS™ and SmPill™, which not structurally diverse post-translational the storage and annotation of experimental plaques.

Since plaques are pathologic Conway Fellow, Professor Denis Shields has progression was associated with gross stable Aβ dimers strongly correlates data.The The integration ofnext next generation modification ofthe proteins.

More than halfofofall allof Taylor’s collaboration Sigmoid Pharma has only enhance solubility and permeability modification of proteins.

More than half data. integration ofwith generation hallmarks of AD, it had been assumed with thebeen presence of further AD-type determined that there is no clear evidence deletions in the nefwill gene. gene products have been shown to be bioinformatic tools will further thedementia. certainly successful by these metrics with the drug but can deliver it to targeted locations bioinformatic tools the gene products have been shown to be that they alsodefective caused the disease.

These exciting findings buildtoondate earlier that viral sequences in three co-authored publications glycosylated.

Withmany many specific glycans or development unified approaches forin two of in theparticular gastrointestinal tract, including theor glycosylated.

With specific glycans development ofofunified approaches for However, much of the research in the area to publications from the Walsh group the HIV-1 nef gene or certain regions the highest ranking journals in the glycoforms showing potential as cancerof the handling large scalescientific glycomics data initiatives colon. glycoforms showing potential as cancer handling large scale glycomics data initiatives date has been based on observational or case However, the quantity and temporal protein play a significant role in disease that SDS-stable Aβ dimers can impair field, Gastroenterology and Proceeding of the biomarkers, there anincreasing increasing need withapplications applications biomarkersystematic discovery biomarkers, there isisan need toto with ininbiomarker discovery studies rather than rigorous, progression of amyloid plaques do not The Sigmoid Pharma-Taylor collaboration is progression. neuronal functions necessaryasfor National Academy of Sciences, well as the develophigh highthroughput, throughput,highly highlysensitive sensitiveand and develop scientific evaluation.

This work by doctoral facilitating the development of a new Thisresearch research waspartially partially supported by This supported by generation of was proprietary innovative products robust strategies thatdetail detail the glycomeofof robust strategies that glycome HIV-infected patients can bethe categorised candidate Ravindra Pushker set out to therapeutic approach for the treatment ofon and the creation of high-skilled jobs. the basis of the number of years it takes for determine in a substantially larger sample set inflammatory bowel disease (IBD) by bringing them to progress to AIDS. Some patients if anythan association exists between disease More 15,000 people in Ireland and together the research methodology of the maintain stable CD4 progression and particular acid with the millions of people worldwideamino are living Taylor group with thelymphocyte proprietary counts and The signalling pathway that Fbxw7-dependent results in both academic outputs Irish biopharmaceutical development do not go on to drug develop AIDS evenoriginates after more differences or deletions within theand nefthe gene. symptoms IBD today.degradation.

Current therapeutic liquid/emulsion delivery system, from transforming growth factorapplication of research toward clinical product company, Sigmoid Pharma recently scooped than 10 years of infection. options for this chronic debilitating disease are LEDDS®, developed by Sigmoid Pharma. disease andbasis, improve treatment, Conway researchers ledofby Tara On a per therepatient wasofno excess of beta (TGFβ) controls important TGIF1 is(CKD) apatient negative regulator TGFβ development with indigenous the overall Innovation theDr. Year award at very limited with surgery oftencompanies.” being the only McMorrow and Professor Michael Ryan have with particular focus on CKD arising from Scientists are curious as to why these longLTNP patients with one or more defective nef Commenting on theTimes award, Professor Taylor the inaugural Irish cellular processes suchAll-Island as growth, signalling andThe theSigmoid Ericsson groupcurrently now viable option. product, most likely die as aTaylor ofofprogressors. the raised New led Conway Dr Commenting on the collaboration, Dr term,research non-are progressor (LTNP) patients do not sequences when compared to diabetes andto The multisuccessfully secured €485,500 in funding as most likely tohypertension. die asinactivation aresult result theof raised New research ledby byThe Conway Fellow Dr said, “We delighted for Dr Fellow Coulter and his Innovation Awards. life-science SME, differentiation and apoptosis.

A wide demonstrate that in a phase II clinical study, uniquely enables glucose levels seen inin diabetes.

Breandán Kennedy indicates that treatment Coulter said, “The collaboration with the Taylor develop AIDS. This may reflect differences in While the high frequency of amino acid disciplinary research consortium has 25 part of an overall award to the Systems team and indeed it reflects well on our glucose levels seen diabetes.

Breandán Kennedy indicates that treatment foundedofbyhuman UCD pharmacology graduate, Dr range disorders, including Fbxw7 results the accumulation of oral delivery of ainpowerful drug without of diabetic blindness should look at laboratory demonstrates theispotential the host, viral genetics or replacement at particular residues indicative partners (16clearly universities, 9found industry partners) Biology towards Novel Chronic Kidney partnership.

Ahas key driver ofenvironmental successful Ivan Coulter, actively collaborated of diabetic blindness should look at with Dr Kennedy and his team thatTGFβnew blood causing systemic side-effects. vascular disease and cancer, display TGIF1 within cells and reduced protecting the neurons responsible for colour that can be realised through focused Dr Kennedy and his team found that new factors that could potentially be exploited for of rapid evolvement, permutation testing from 15and countries and thecell project isindue toblood run Disease Treatment (SysKid) scientific research inand 2010 isCormac meaningful Conway Diagnosis Fellow, Professor Taylor protecting the neurons responsible for colour vessels the neuronal death diabetic dysfunctional TGFβ signalling. dependant signalling.

Inthe addition, they vision in theof eye and not justindustry targeting the application of basic research.

The development vessels and the neuronal cell death in diabetic the treatment of the disease. showed that residues with more replacements Under normal conditions, gastrointestinal for five years. interaction academia with that consortium under the European Union FP7 since being granted a Science Foundation vision in the eye and not just targeting the retinopathy can arise independently of each demonstrate that TGFβ signalling is blood vessels as research is currently the practice. of a smart economy will depend on like-minded than expected statistically significant. retinopathy canwere arisenot independently of each programme.

Ireland industry partnership award blood as organisms is currently the shown practice. other.

In addition, theycells identified cone Studiesvessels in led model have Research by Conway Fellow and that disturbed inpartners cancer withthat mutations The UCD team, including postdoctoral collaborative opportunities other.

In Conway addition, theyidentifying identified that cone in 2004. photoreceptor neurons, those involved in Nearly 2.5 million people worldwide are blind infection with nef-deficient virus shows anto The researchers conclude thatand current data and realising basic and applied research researchers Dr. Craig Slattery Dr. Natalia Syskid (www.SysKid.eu) was established SFI Stokes Professor, Dr Johan Ericsson in the Fbxw7 gene. photoreceptor neurons, those involved in Nearly 2.5 million people worldwide are blind colour vision and used in daylight, are most due to diabetic retinopathy.

Thisand secondary provides no evidence that individual residues attenuated course of infection some The Irish Times award recognises the stellar synergies.

This collaboration, initiated through Martin, will utilise cell culture and animal further our understanding ofThis chronic kidney has identified the tumour suppressor colour vision and used in daylight, are most due to diabetic retinopathy. secondary affected by the high glucose levels. complication of diabetes of activates thePharma growthin innovative performance Sigmoid aaffected SFI research the Fbxw7 as a blood novel regulator of eye TGFβ Dr Maria a senior byBengoechea-Alonso, thesupplement, high glucosehighlights levels. complication of diabetes activates theand growth of newapplication leaky inand the is their of vessels research development. potential that team innovative indigenous companies The research made their observations signalling.

The findings, published in postdoctoral researcher in the group, of new leaky blood vessels in the eye and is responsible forhas the developed death of photoreceptors, The company two new drug working with“When academia can realise.”

The research team made their using a novel zebrafish model ofobservations diabetes, Oncogene, describe the explained, TGIF1 accumulates responsible for the death ofmechanism photoreceptors, the neurons that send visual messages toby ournot technologies, LEDDS™ and SmPill™, which using a novel zebrafish model of of diabetes, which resembles the early stages diabetic which Fbxw7 regulates this important in cells,collaboration it recruits other proteins to the that send visual messages to ourof Taylor’s with Sigmoid Pharma has brain. onlyneurons enhance the solubility and permeability whichdown resembles the early stages of non diabetic retinopathy inthe humans.

Itshown is an exciting Meta-analysis by UCD researchers led by studies in humans have that signalling cascade.Fbxw7 acts by marking shut transcription of TGFβbrain. certainly been successful by these metrics with the drug but can deliver it to targeted locations retinopathy in It iswho an exciting development forhumans. the group now hope to Until now, it was unclear if the changes to has Conway Fellow, Professor Shields progression was associated with gross target proteins for destruction.

In the three co-authored publications to date in two dependent target genes”.Recent work in of in the gastrointestinal tract, Denis including further extend their and establish vessels andneeds occurred independently development for theresearch group who now hope Until now, itneurons was there unclear ifnothe changes to of Glycomics thethe supporting framework cells, tissues and fluids. determined that isauthors clear evidence deletions inranking the nef gene. the highest scientific journals in the their manuscript, identify the Ericsson laboratory has described aato colon. model of late stage diabetic disease. one other and which type of retinal neuron is further extend their research and establish a vessels and neurons occurred independently of extensive, well-curated databases and in of that particular defective viral sequences field, Gastroenterology and Proceeding of the transforming growth factor-beta induced number ofmuch new targets, Commercial packages that support HPLC However, ofFbxw7 the research in including the area to The Sigmoid isis model ofAcademy late stage diabetic disease. one other and which of collaboration retinal neuron flexible analytical tools.

Currently, thisoffield the HIV-1 nefPharma-Taylor gene oratype certain regions the National offacilitate Sciences, as well as the factor 1 (TGIF1) as new target for SREBP1 and C/EBPβ, both of which are instruments cannot the extraction of date has been based on observational or case facilitating theathe development of ainnew of study play lacks established, protein significant role disease generation of proprietary products large quantities of data.

Ininnovative an effort to alleviate studies rather than rigorous, systematic therapeutic approach for the treatment comprehensive and centralised data of progression. and the creationwithin of high-skilled jobs. this bottleneck high-throughput scientific evaluation.

This work by doctoral inflammatorystandards bowel disease (IBD) by bringing collections, and information glycomic the NIBRT team HIV-infected patients can be categorised candidate Ravindra Pushker set outhave to More thanprojects, 15,000 people in Ireland and together the research methodology reporting protocols that exist withinof theon developed web-based tool that the basis of the number of years it takes for determine a substantially larger sample millions ofain people worldwide are interfaces living withset the Taylor group with the proprietary genomics and proteomics. with theassociation Waters chromatography software them to progress to AIDS. Some patients if any exists between disease symptoms IBD today.

Current therapeutic

EU, SFI and HRB) aimed at developing

“When we applied thesemolecules, new drugs towhich our IBD antibodies and small model, was tricked into thinking that it bind tothe Aβgut dimers and neutralise their was being deprived of oxygen.

This activated activity, are ongoing. protective pathways, which in turn prevented Reference the death of the cells that line the The presence of sodium dodecyl sulphate-stable gastrointestinal tract,” explained ProfessorAb of HIVis nef are associated critical in with determining the rate dimers strongly Alzheimer-type Taylor.

“Our pre-clinical trial data now dementia.

Jessica M. Mc Donald, Georgecan M. Savva, of disease progression.

Professor Denis inform the next phase Sigmoid Pharma product Carol Brayne, Alfred that T. Welzel, Gill Forster, Ganesh M.of Shields believes searches for modifiers development pipeline”.

Shankar, Dennis J. Selkoe, Paul G. Ince and Dominic progression rates should now focus on other M. Walsh on behalf of the Medical Research Council host andFunction viral factors.

“Systematic evaluation In addition to the product is Brain currently Cognitive and Ageingthat Study.

2010: in of large quantities of data by bioinformatics phase II clinical studies, Sigmoid Pharma is 133; 1328–1341 can be justaas important inCampbell refuting developing LEDDS™-enabled formulation of NIBRT researchers DrMatthew MatthewCampbell andDrDrNatalia Natalia NIBRT researchers Dr and Artemenko whodeveloped developed GlycoExtractor hypotheses that are current in the literature, as Artemenko who GlycoExtractor the hydroxylase inhibitor it is in discovering unknown patterns”, said. dimethyloxaloylglycine (DMOG) to bring he about effective, safe and targeted delivery of this This research was funded through Science potential therapeutic agent.

Foundation Ireland and University College involved in with the production of fat cells. tract is lined cells that block the contents Dublin.

Interestingly, anotherinto group of scientists of the gut from leaking the intestine.

In an models to demonstrated identify processes involved recently that TGIF1 isearly also IBD patient, this barrier is broken and in the CKD progression and investigate novel contents ofinthe gut leak out into surrounding involved adipogenesis.

Taken together, Commenting on the research, DrDrKennedy strategies for preventing and slowing the used Commenting on the research, Kennedy areas.

The research team in UCD these results may point to anConway important Reference: said, “By establishing a robust model early progression of the disease.

These studies will arole model of IBD and, by applying aHIV-1 newfor class of said, “By establishing acell robust for early for Fbxw7 inthe fat differentiation Meta-analysis to test association ofmodel nef amino be integrated with clinical andinhibitors, epidemiological and late stage diabetic retinopathy, we would drugs known as hydroxylase acid and deletionsretinopathy, with of disease progression. anddifferences late stage diabetic we were would and opens the possibility Fbxw7 studies across the consortium using systems hope to better understand the progression of Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields. able to to reverse the hope bettercompletely understand the to progression of being aalmost novel target forp3644-3653 obesity drugs. biology methodologies in order develop new Journal of Virology, Apr 2010 the disease the way for identifying symptoms ofand thepave disease. the disease and pave the way for identifying Professor Ericsson now proposes to useto diagnostic strategies treatment options new drug targets for and its successful treatment”. new drug targets for itsnew successful treatment”. advanced transcriptomic techniques “When we these drugs to ourto IBD prevent CKDapplied development.

Email The research was funded through Science model, theall gut was tricked into thinking that it identify the genes regulated by TGIF1 tara.mcmorrow@ucd.ie for details of a PhD The research was funded Science Foundation Ireland and the through Health was being deprived of oxygen. activated position currently available. during the differentiation ofThis fatResearch cells.

Foundation Ireland and theinHealth Research Board. protective pathways, which turn “By identifying these genes, weprevented hope to Board. the death of theunderstanding cells that line the enhance our of adipocyte gastrointestinal explained Professor differentiationtract,” and the roles of Fbxw7 and Reference: Taylor.

“Our pre-clinical trial data can now TGIF1 in this process”.

Reference: Predominant dysfunction in aproduct inform the cone next photoreceptor phase Sigmoid Pharma of HIV nef are critical in determining the hyperglycaemic model of non-proliferative diabetic Predominant cone photoreceptor dysfunction in arate development pipeline”.

Reference of diseaseYolanda progression.

Professor retinopathy.

Alvarez, Jenneth Chen, Denis Alison hyperglycaemic model of non-proliferative diabetic Tumor suppressor Fbxw7 regulates TGFβ signaling EUROCarbDB, a research infrastructure design Reynolds, Nore John J. O’Connor, Breandan Shields believes searches modifiers retinopathy.

Yolanda Alvarez, Jenneth Chen, Alison In addition toWaghorne, the product that isfor in of by targeting TGIF1 forthat degradation.

M Tcurrently BengoecheaKennedy.

Disease Models & Mechanisms (2010) study funded by the EU 6th Framework Reynolds, Nore Waghorne, John J. O’Connor, Breandan progression rates should now focus on other phase II clinical studies, Sigmoid Pharma is Alonso, J Ericsson. Oncogene (12 July 2010) Programme. users formulation can (2010) access the Kennedy.

Models &“Systematic Mechanisms host andDisease viral factors. evaluation doi:10.1038/onc.2010.278 developing a Prospective LEDDS™-enabled of GlycoExtractor tool ondata by bioinformatics of large quantities of the hydroxylase inhibitor http://glycobase.nibrt.ie:8080/DemoGlycoExtra can be just as important in refuting dimethyloxaloylglycine (DMOG) to bring about ctor/mainPage. hypotheses currentdelivery in the literature, effective, safethat andare targeted of this as it is in discovering Reference potential therapeuticunknown agent. patterns”, he said.

Bioinformatic analysis of HIV progression studies

Conwayofcollaborator scoopsidentified Irish Times Innovation Award New regulator TGFβ signalling Success in EU FP7 call

Zebrafish Zebrafish model model gives gives insights insights into into diabetic diabetic blindness blindness

Bioinformatic analysis of HIV progression studies GlycoExtractor advances glycan data manipulation

GlycoExtractor: A web-based interface for high This research was offunded through processing HPLC-Glycan dataScience throughput