A new look at the solid-liquid interface ... Conway Focus Summer 2014 final.pdf · ElaineQuinn...

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Elaine Quinn Communications & Education Officer UCD Conway Institute of Biomolecular & Biomedical Research University College Dublin Belfield, Dublin 4 Ireland E: [email protected] T: (+353-1) 716 6706 F: (+353-1) 716 6701 W: www.ucd.ie/conway Investing in Your Future september 2007 Issue 1 Research by Conway Fellow, Dr Oliver Blacque has revealed new information about a gene implicated in Joubert syndrome and related cerebellar disorders (JSRDs), characterised by blindness, bone abnormalities, cystic kidneys, developmental delay and loss of muscle tone and control. The findings of this research, funded through a Science Foundation Ireland President of Ireland Young Researcher Award (PIYRA) to Oliver Blacque, were recently published in the Journal of Cell Biology. One of seven genes associated with JSRDs, Arl13b codes for a protein already known to play roles in the formation and/or function of cilia, which are hair-like projections extending from the surface of the cell. However, the precise molecular details of what exactly Arl13b is doing in cilia have remained unclear. Blacque’s team studied the gene in the cilia of tiny worms (Caenorhabditis elegans) while collaborators in the University of Tokyo conducted parallel experiments in cultured human cells. Together, they confirmed that Arl13b proteins uses lipid anchors to associate with the ciliary membrane. Much of the work on the project was carried out by UCD doctoral candidate, Sebiha Cevik. She and her colleagues went on to demonstrate in C. elegans how disrupting the function of worm Arl13b causes the ciliary membrane to bulge and become misshapen as well as affecting the ability of other proteins to properly distribute within the ciliary membrane. They also found that a fully functional Arl13b protein is needed for the normal functioning of a protein transport system in cilia. This intraflagellar transport system (IFT) makes contact with the ciliary membrane. Based on these results, they proposed a new working model for Arl13b, where it functions at the ciliary membrane to regulate important ciliary membrane properties such as shape, transmembrane protein distributions and IFT. Up to only 20 years ago, many believed most cilia to be redundant cellular organelles that have fallen victim to mammalian evolution - a type of cellular appendix. We now know that these cellular antennae present on nearly all of our cells and serve fundamental roles in many motility and sensory functions, including signalling pathways critical to development. It is now not surprising that defects in cilium structure and function are associated with an ever expanding range of human diseases and syndromes, collectively called ciliopathies, which have overlapping clinical features such as polycystic kidneys and livers, retinal degeneration, bone abnormalities, hydrocephalus, as well as complex traits including obesity, diabetes, mental retardation and even cancer. Dr Oliver Blacque hopes that these findings will ultimately lead to a greater understanding not only of JSRDs, but also of closely related ciliopathies such as Meckel Gruber and Bardet-Biedl syndrome, as well as perhaps more common phenotypes associated with cilium dysfunction such as mental retardation and obesity. He notes “That Arl13b associates with ciliary membranes and is required for cilium structure/function in both worms and mammals demonstrates the remarkable evolutionary conservation of how this small G-protein functions.” Reference Joubert syndrome Arl13b functions at ciliary membranes and stabilizes protein transport in Caenorhabditis elegans. Cevik S, Hori Y, Kaplan OI, Kida K, Toivenon T, Foley-Fisher C, Cottell D, Katada T, Kontani K, Blacque OE. J Cell Biol. 2010 Mar 22; 188(6):953-69 May 2010 Issue 10 I am delighted to welcome you to the Conway Focus and look forward to working with you in the coming months! As an institute with an increasingly interdisciplinary research focus and expertise in specialist technology platforms, we are uniquely placed to participate in the education and training of the next generation of research scientists. The newly launched PhD programme in Bioinformatics and Systems Biology recently attracted 80 EU and 120 non-EU applicants for up to 15 studentships. We introduced 4 new advanced core technology modules on a pilot basis this academic year; those covering principles and practical aspects of imaging and applied proteomics began in late March and will run until mid-June with a further two modules in genomics and flow cytometry taking place over week-long periods during the summer months. We hope to determine from this pilot if demand for training from within UCD as well as from external academic centres and industry will dictate stand-alone delivery of these advanced modules or inclusion within larger programmes such as the new MSc in Imaging commencing in September 2010. I hope that a number of new initiatives, including the early-stage researcher forum described in this issue, will not only strengthen the community of Conway researchers and forge new interdisciplinary links but will celebrate and heighten awareness of our research and innovation successes. Professor Walter Kolch Director, UCD Conway Institute Director’s Message Worm research reveals cilia disease gene function UCD CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH Arl13b at ciliary membrane Centre of Excellence hosts international workshop As a European Centre of Excellence, the Department of Rheumatology in St Vincent’s University Hospital was chosen to host an international two-day workshop on March 26th & 27th 2010. Sponsored by Roche Pharma, the Participate workshop gave twenty rheumatologists from centres in Europe and Australia the opportunity to witness the care of patients with rheumatoid arthritis (RA) at St Vincent’s. The Participate programme focused on advanced treatment regimens for RA in the clinic, including practical aspects of biologic therapy carried out in the accredited infusion suite that provides optimal care for RA patients. In addition to lectures from Conway Fellows, Professors Oliver FitzGerald and Douglas Veale, delegates heard from clinical nurse specialists about patient education, screening and monitoring of biological therapies. Addressing the international guests, Ms Mary Duff, Director of Nursing and Ms. Kay Connolly, Assistant Director of Nursing for the Bone & Joint Unit expressed their hope that the experience of the multidisciplinary team from St Vincent’s would provide a template for delegates to reproduce similar care and facilities for the management of RA patients in their respective countries. Launch of Conway postdoctoral & graduate forum A new fortnightly forum for Conway graduate and postdoctoral researchers will be launched in May 2010. This initiative will give early- stage researchers the opportunity to talk about science and issues that concern them in an informal environment with refreshments provided! Content for the forum will be decided by the members but it is envisaged that it will include a mix of technology overviews, informal and formal research seminars, PhD viva rehearsals and career development talks from within and beyond academia. Forum committee members, PhD student Mr Thomas Schwarzl ([email protected] ) and postdoctoral researchers, Dr David Gomez ([email protected]) and Dr Craig Slattery ([email protected] ) invite suggestions for the forum schedule. Frog peptide structure selected for journal cover An image of the frog peptide structure central to the work of a UCD Conway research team was selected as the front cover image for the April 2010 edition of the scientific journal, Biochimica et Biophysica Acta (BBA); Proteins & Proteomics. Peptides in the skin of many species of frog have anti-bacterial and anti-fungal properties as well as the ability to lyse or rupture mammalian cells. This innate immunity protects it from attack. These properties of frog skin peptides are exciting from the prospect of being developed into therapeutically valuable anti-infective and anti- cancer agents. Conway Fellow, Dr Chandralal Hewage and his team carried out molecular modelling of the XT-7 peptide and its analogue [G4K]XT-7 in a variety of solutions in order to understand the structural basis for the difference in biological activity. This particular XT-7 peptide, isolated from the skin of Silurana tropicalis, shows potential for drug development as it has impressive activity against the growth of bacteria and Candida albicans. However, this potential as an anti- infective agent is restricted by its haemolytic activity. A change to the amino acid structure of the XT-7 peptide can create an analogue that retains anti-infective properties but without the complicating haemolytic activity. The single amino acid substitution (glycine replaced by lysine) improves the therapeutic potential of this naturally occurring peptide. Cover of April 2010 edition of Biochimica et Biophysica Acta (BBA); Proteins & Proteomics. A new look at the solid-liquid interface Interesting things happen at interfaces and where solids meet liquids is no exception. Understanding the complex phenomena taking place at the ‘solid- liquid’ interface could give important clues about how to build better medical devices and longer-lasting batteries, but to date it has been difficult to get a handle on how chemical ions in solution behave at this crucial juncture. Until now, that is. A team led by UCD scientists has developed a new tool to build up a clearer picture of what is going on at this interface, and crucially, can do this on the nanoscale. The procedure, published in Nature Communications, stands to enable research in biological and materials science. “The solid-liquid interface is the location of many important physical, biological and chemical processes,” explains researcher Liam Collins, who is completing a Ph.D. in the Nanoscale Function Group. “If you want to understand biosystems, diseases and novel biomaterials or processes in energy systems like batteries, you need to understand what happens at the solid-liquid interface.” What happens on the atomic level at this interface can have an impact at a more visible or macroscopic level - the way the body functions, or how quickly a battery drains, for example - so techniques that can operate on atomic-length scales can improve our fundamental understanding of materials and devices, notes Collins, who works with Conway Fellow, Dr Brian Rodriguez. Existing techniques, such as the atomic force microscope, already allow researchers to get a good ‘view’ of physical structures at the solid-liquid interface but not how ions behave at this interface, he explains: “So we set out to join structural informa- tion with electrochemical function.” To get this multi-modal view, Collins worked with colleagues in UCD, Oak Ridge National Laboratory, USA and Taras Shevchenko Kiev National University, Ukraine to develop a technique called electrochemical force microscopy (EcFM). The benefit of the new technique is that it allows researchers to get a clearer picture of what is going on at this key solid-liquid interface in situ rather than making measurements in air and extrapolating to liquids, explains Collins.The team are now turning their attention to new materials, one being a form of ultra-thin carbon called graphene, which has applications in energy storage. “Probably the immediate improve- ment coming out of this EcFM technique will be a better understanding of energy systems such as double-layer capacitors and lithium ion batteries,” says Collins. “If we can understand the processes on the nanoscale here, it will in turn allow us to improve the efficiency and lifetime of devices.” He also has an eye to a wide range of longer-term applications that could come from better understanding the relationship between structure and function in biologi- cal systems. “That may help us to develop in vivo batteries that harness biofuels, or to understand diseases like Alzheimer’s disease, at a fundamental level.” (In conversation with journalist, Claire O’Connell for UCD Science showcase) Director’s Message Welcome! Under the latest round of the Science Foundation Ireland Investigator Programme, seven research projects led by UCD and one partnered with Teagasc will receive funding. This is the joint highest number of research projects from any one institution to receive funding under this round and five of these projects will be led by Conway Fellows. Congratulations to them and to the many other Fellows who continue to secure funding in an increasingly competitive and challenging environment. I was delighted to welcome UCD President, Professor Andrew Deeks to the Institute at the beginning of May and for Conway Fellows to have the opportunity to highlight their contributions to research excellence, innovation and outstanding scholarship in the University. Congratulations to Conway researchers and alumni who have been actively organising and participating in science engagements activities such as Pint of Science, Soapbox Science, and Engage. Your passion for research and willingness to reach audiences outside of your peers will help to embed science firmly within society. Professor Walter Kolch Director Issue 22, Summer 2014 From a patient perspective, tablets are preferable to injections when it comes to taking medication. The pharmaceutical company, Unigene (NJ, USA) have designed a proprietary tablet formulation of calcitonin, an anti-osteoporosis drug that is usually injected. UCD researchers led by Conway Fellow, Prof David Brayden have revealed the role played by one ingredient in this new tablet, an additive called citric acid, in enabling oral delivery of calcitonin. Normally, calcitonin is broken down in the gut as it is a small protein (peptide) and unable to permeate the gut wall to reach the blood. In collaboration with Novo-Nordisk and Copenhagen University, the team showed that citric acid in the tablet acted only to prevent breakdown and not to increase permeation across the epithelium of the gut. The finding means that there was no permeation enhancer in the calcitonin tablet and that the data achieved in phase III clinical trials by Unigene arose simply from preserving calcitonin intact using agents approved in other products and presenting it to the gut wall in the small intestine region. Prof David Brayden explained, “We worked out that the concentration of the peptide reaching the blood from oral administration was no more than 2%, which is still enough to compete with nasal competitor products for such a potent and exceptional agent. However, in future, less potent peptide products would need enhancers to get higher percentages of peptide to the blood and this has toxicological implications.” Enabling oral drug delivery In Brief Reference Welling SH et al. The role of citric acid in oral peptide and protein formulations: Relationship between calcium chelation and proteolysis inhibition. Eur J Pharm Biopharm. 2014 Apr;86(3):544-51. doi: 10.1016/ j.ejpb.2013.12.017. All living organisms require enzymes that are biological catalysts. These catalysts speed up biological reactions so life is possible. Under biological conditions, it would take about 7,000 years for just half of peptide bonds in a protein to be digested. Fortunately, proteolytic enzymes such as chymotrypsin allow us to digest proteins in hours rather than years. A recent publication from the group led by Conway Fellow, Prof J.P.G Malthouse examines how chymotrypsin can speed up reactions by a factor of one thousand million. The team found that one of the mechanisms chymotrypsin uses is to increase the reactivity of its active site hydroxyl group by ~100,000 times. Reproductive performance of cows affects the efficiency of milk and beef production because of its influence on the calving to first service interval, subsequent calving pattern, length of lactation and culling rate, and culling rates for failure to conceive. A recent publication from Conway Fellow, Prof Mark Crowe updates earlier reviews on the topic of reproductive efficiency in dairy and beef cows and focuses on factors contributing to resumption of ovulation and affecting uterine health in postpartum dairy and beef cows. In Pictures Reference Collins L et al. Probing charge screening dynamics and electrochemical processes at the solid–liquid interface with electrochemical force microscopy. Nature Communications| 5:3871| DOI:10.1038/ ncomms4871. In seasonally calving herds, the aim is to achieve conception by 75 to 85 days, depending on breed, following parturition so that calving-to-calving intervals are maintained at 365 days. Reference Cleary JA, Doherty W, Evans P, Malthouse JP. Hemiacetal stabilization in a chymotrypsin inhibitor complex and the reactivity of the hydroxyl group of the catalytic serine residue of chymotrypsin. Biochim Biophys Acta. 2014 Jun;1844(6):1119-27. doi: 10.1016/ j.bbapap.2014.03.008. Epub 2014 Mar 21. M. A. Crowe, M. G. Diskin and E. J. Williams. Parturition to resumption of ovarian cyclicity: comparative aspects of beef and dairy cows. Animal (2014) Mar 28: 1 -14 Field testing eCDSS (electronic clinical descion support system) for connectivity in rural northern Malawi (l-r) Dr Chris Watson (UCD) and Dr John O’Donoghue (Imperial College London) as part of Managing Type 2 Diabetes in Malawi, Africa (MTIMA) project. Dr Lorna Lopez (Cagney group) partners with her neuron teddy to give “Clues to understanding your brain” as part of Soapbox Science Dublin 2014 Aine Lawlor launches ICORG’s first awareness campaign for International Clinical Trials Day with her assistants in the Institute.

Transcript of A new look at the solid-liquid interface ... Conway Focus Summer 2014 final.pdf · ElaineQuinn...

Elaine QuinnCommunications & Education Officer

UCD Conway Institute of Biomolecular & Biomedical ResearchUniversity College Dublin

Belfield, Dublin 4Ireland

E: [email protected]: (+353-1) 716 6706F: (+353-1) 716 6701

W: www.ucd.ie/conway

Investing in Your Future

septem

ber2

007

Issue1

Research by Conway Fellow, Dr OliverBlacque has revealed new informationabout a gene implicated in Joubertsyndrome and related cerebellar disorders(JSRDs), characterised by blindness, boneabnormalities, cystic kidneys,developmental delay and loss of muscletone and control. The findings of thisresearch, funded through a ScienceFoundation Ireland President of IrelandYoung Researcher Award (PIYRA) to OliverBlacque, were recently published in theJournal of Cell Biology.

One of seven genes associated with JSRDs,Arl13b codes for a protein already known toplay roles in the formation and/or functionof cilia, which are hair-like projectionsextending from the surface of the cell.However, the precise molecular details ofwhat exactly Arl13b is doing in cilia haveremained unclear.

Blacque’s team studied the gene in the ciliaof tiny worms (Caenorhabditis elegans)while collaborators in the University ofTokyo conducted parallel experiments incultured human cells. Together, theyconfirmed that Arl13b proteins uses lipidanchors to associate with the ciliarymembrane.

Much of the work on the project was carriedout by UCD doctoral candidate, SebihaCevik. She and her colleagues went on todemonstrate in C. elegans how disrupting

the function of worm Arl13b causes theciliary membrane to bulge and becomemisshapen as well as affecting the ability ofother proteins to properly distribute withinthe ciliary membrane.

They also found that a fully functionalArl13b protein is needed for the normalfunctioning of a protein transport system incilia. This intraflagellar transport system(IFT) makes contact with the ciliarymembrane. Based on these results, theyproposed a new working model for Arl13b,where it functions at the ciliary membraneto regulate important ciliary membraneproperties such as shape, transmembraneprotein distributions and IFT.

Up to only 20 years ago, many believedmost cilia to be redundant cellularorganelles that have fallen victim tomammalian evolution - a type of cellularappendix. We now know that these cellularantennae present on nearly all of our cellsand serve fundamental roles in manymotility and sensory functions, includingsignalling pathways critical to development.

It is now not surprising that defects incilium structure and function are associatedwith an ever expanding range of humandiseases and syndromes, collectively calledciliopathies, which have overlapping clinicalfeatures such as polycystic kidneys andlivers, retinal degeneration, boneabnormalities, hydrocephalus, as well as

complex traits including obesity, diabetes,mental retardation and even cancer.

Dr Oliver Blacque hopes that these findingswill ultimately lead to a greaterunderstanding not only of JSRDs, but alsoof closely related ciliopathies such asMeckel Gruber and Bardet-Biedl syndrome,as well as perhaps more commonphenotypes associated with ciliumdysfunction such as mental retardation andobesity.

He notes “That Arl13b associates with ciliarymembranes and is required for ciliumstructure/function in both worms andmammals demonstrates the remarkableevolutionary conservation of how this smallG-protein functions.”

ReferenceJoubert syndrome Arl13b functions at ciliarymembranes and stabilizes protein transport inCaenorhabditis elegans. Cevik S, Hori Y, Kaplan OI,Kida K, Toivenon T, Foley-Fisher C, Cottell D, Katada T,Kontani K, Blacque OE. J Cell Biol. 2010 Mar 22;188(6):953-69

May2010Issue10

I am delighted to welcome you to theConway Focus and look forward to workingwith you in the coming months!

As an institute with an increasinglyinterdisciplinary research focus andexpertise in specialist technology platforms,we are uniquely placed to participate in theeducation and training of the nextgeneration of research scientists. The newlylaunched PhD programme in Bioinformaticsand Systems Biology recently attracted 80EU and 120 non-EU applicants for up to 15studentships.

We introduced 4 new advanced coretechnology modules on a pilot basis thisacademic year; those covering principlesand practical aspects of imaging and appliedproteomics began in late March and will rununtil mid-June with a further two modules ingenomics and flow cytometry taking placeover week-long periods during the summermonths.

We hope to determine from this pilot ifdemand for training from within UCD as wellas from external academic centres andindustry will dictate stand-alone delivery ofthese advanced modules or inclusion within

larger programmes such as the new MSc inImaging commencing in September 2010.

I hope that a number of new initiatives,including the early-stage researcher forumdescribed in this issue, will not onlystrengthen the community of Conwayresearchers and forge new interdisciplinarylinks but will celebrate and heightenawareness of our research and innovationsuccesses.

Professor Walter KolchDirector, UCD Conway Institute

Director’s Message

Worm research reveals cilia disease gene function

UCD CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH

Arl13b at ciliary membrane

Centre of Excellence hosts international workshop

As a European Centre of Excellence, theDepartment of Rheumatology in St Vincent’sUniversity Hospital was chosen to host aninternational two-day workshop on March26th & 27th 2010. Sponsored by RochePharma, the Participate workshop gavetwenty rheumatologists from centres inEurope and Australia the opportunity towitness the care of patients with rheumatoidarthritis (RA) at St Vincent’s.

The Participate programme focused onadvanced treatment regimens for RA in theclinic, including practical aspects of biologictherapy carried out in the accredited infusionsuite that provides optimal care for RApatients. In addition to lectures from ConwayFellows, Professors Oliver FitzGerald andDouglas Veale, delegates heard from clinicalnurse specialists about patient education,screening and monitoring of biologicaltherapies.

Addressing the international guests, Ms MaryDuff, Director of Nursing and Ms. KayConnolly, Assistant Director of Nursing for theBone & Joint Unit expressed their hope thatthe experience of the multidisciplinary teamfrom St Vincent’s would provide a template fordelegates to reproduce similar care andfacilities for the management of RA patients intheir respective countries.

Launch of Conway postdoctoral & graduate forum

A new fortnightly forum for Conway graduateand postdoctoral researchers will be launchedin May 2010. This initiative will give early-stage researchers the opportunity to talk aboutscience and issues that concern them in aninformal environment with refreshmentsprovided! Content for the forum will be

decided by the members but it is envisagedthat it will include a mix of technologyoverviews, informal and formal researchseminars, PhD viva rehearsals and careerdevelopment talks from within and beyondacademia. Forum committee members, PhDstudent Mr Thomas Schwarzl

([email protected] ) and postdoctoralresearchers, Dr David Gomez([email protected]) and Dr Craig Slattery([email protected] ) invite suggestions forthe forum schedule.

Frog peptide structure selected for journal cover

An image of the frog peptide structure centralto the work of a UCD Conway research teamwas selected as the front cover image for theApril 2010 edition of the scientific journal,Biochimica et Biophysica Acta (BBA);Proteins & Proteomics.

Peptides in the skin of many species of froghave anti-bacterial and anti-fungal propertiesas well as the ability to lyse or rupturemammalian cells. This innate immunityprotects it from attack. These properties offrog skin peptides are exciting from theprospect of being developed intotherapeutically valuable anti-infective and anti-cancer agents.

Conway Fellow, Dr Chandralal Hewage and histeam carried out molecular modelling of theXT-7 peptide and its analogue [G4K]XT-7 in a

variety of solutions in order to understand thestructural basis for the difference in biologicalactivity.

This particular XT-7 peptide, isolated from theskin of Silurana tropicalis, shows potential fordrug development as it has impressive activityagainst the growth of bacteria and Candidaalbicans. However, this potential as an anti-infective agent is restricted by its haemolyticactivity.

A change to the amino acid structure of theXT-7 peptide can create an analogue thatretains anti-infective properties but without thecomplicating haemolytic activity. The singleamino acid substitution (glycine replaced bylysine) improves the therapeutic potential ofthis naturally occurring peptide.

Cover of April 2010 edition of Biochimica et BiophysicaActa (BBA); Proteins & Proteomics.

May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 1

Irish biopharmaceutical developmentcompany, Sigmoid Pharma recently scoopedthe overall Innovation of the Year award atthe inaugural Irish Times All-IslandInnovation Awards. The life-science SME,founded by UCD pharmacology graduate, DrIvan Coulter, has actively collaborated withConway Fellow, Professor Cormac Taylorsince being granted a Science FoundationIreland industry research partnership awardin 2004.

The Irish Times award recognises the stellarinnovative performance of Sigmoid Pharma intheir application of research and development.The company has developed two new drugtechnologies, LEDDS™ and SmPill™, which notonly enhance the solubility and permeability ofthe drug but can deliver it to targeted locationsin the gastrointestinal tract, including thecolon.

The Sigmoid Pharma-Taylor collaboration isfacilitating the development of a newtherapeutic approach for the treatment ofinflammatory bowel disease (IBD) by bringingtogether the research methodology of theTaylor group with the proprietaryliquid/emulsion drug delivery system,LEDDS®, developed by Sigmoid Pharma.

Commenting on the award, Professor Taylorsaid, “We are delighted for Dr Coulter and histeam and indeed it reflects well on ourpartnership. A key driver of successfulscientific research in 2010 is meaningfulinteraction of academia with industry that

results in both academic outputs and theapplication of research toward clinical productdevelopment with indigenous companies.”

Commenting on the Taylor collaboration, DrCoulter said, “The collaboration with the Taylorlaboratory clearly demonstrates the potentialthat can be realised through focusedapplication of basic research. The developmentof a smart economy will depend on like-mindedcollaborative partners identifying opportunitiesand realising basic and applied researchsynergies. This collaboration, initiated througha SFI research supplement, highlights thepotential that innovative indigenous companiesworking with academia can realise.”

Taylor’s collaboration with Sigmoid Pharma hascertainly been successful by these metrics withthree co-authored publications to date in two ofthe highest ranking scientific journals in thefield, Gastroenterology and Proceeding of theNational Academy of Sciences, as well as thegeneration of proprietary innovative productsand the creation of high-skilled jobs.

More than 15,000 people in Ireland andmillions of people worldwide are living with thesymptoms IBD today. Current therapeuticoptions for this chronic debilitating disease arevery limited with surgery often being the onlyviable option. The Sigmoid product, currentlyin a phase II clinical study, uniquely enablesoral delivery of a powerful drug withoutcausing systemic side-effects.

Under normal conditions, the gastrointestinal

tract is lined with cells that block the contentsof the gut from leaking into the intestine. In anIBD patient, this barrier is broken and thecontents of the gut leak out into surroundingareas. The research team in UCD Conway useda model of IBD and, by applying a new class ofdrugs known as hydroxylase inhibitors, wereable to almost completely reverse thesymptoms of the disease.

“When we applied these new drugs to our IBDmodel, the gut was tricked into thinking that itwas being deprived of oxygen. This activatedprotective pathways, which in turn preventedthe death of the cells that line thegastrointestinal tract,” explained ProfessorTaylor. “Our pre-clinical trial data can nowinform the next phase Sigmoid Pharma productdevelopment pipeline”.

In addition to the product that is currently inphase II clinical studies, Sigmoid Pharma isdeveloping a LEDDS™-enabled formulation ofthe hydroxylase inhibitordimethyloxaloylglycine (DMOG) to bring abouteffective, safe and targeted delivery of thispotential therapeutic agent.

Conway collaborator scoops Irish Times Innovation Award

Conway researchers led by Dr. TaraMcMorrow and Professor Michael Ryan havesuccessfully secured €485,500 in funding aspart of an overall award to the SystemsBiology towards Novel Chronic KidneyDisease Diagnosis and Treatment (SysKid)consortium under the European Union FP7programme.

Syskid (www.SysKid.eu) was established tofurther our understanding of chronic kidney

disease (CKD) and improve patient treatment,with particular focus on CKD arising fromdiabetes and hypertension. The multi-disciplinary research consortium has 25partners (16 universities, 9 industry partners)from 15 countries and the project is due to runfor five years.

The UCD Conway team, including postdoctoralresearchers Dr. Craig Slattery and Dr. NataliaMartin, will utilise cell culture and animal

models to identify processes involved in earlyCKD progression and investigate novelstrategies for preventing and slowing theprogression of the disease. These studies willbe integrated with clinical and epidemiologicalstudies across the consortium using systemsbiology methodologies in order to develop newdiagnostic strategies and treatment options toprevent CKD development. [email protected] for details of a PhDposition currently available.

Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Meta-analysis by UCD researchers led byConway Fellow, Professor Denis Shields hasdetermined that there is no clear evidencethat particular defective viral sequences inthe HIV-1 nef gene or certain regions of theprotein play a significant role in diseaseprogression.

HIV-infected patients can be categorised onthe basis of the number of years it takes forthem to progress to AIDS. Some patientsmaintain stable CD4 lymphocyte counts anddo not go on to develop AIDS even after morethan 10 years of infection.

Scientists are curious as to why these long-term, non- progressor (LTNP) patients do notdevelop AIDS. This may reflect differences inthe host, viral genetics or environmentalfactors that could potentially be exploited forthe treatment of the disease.

Studies in model organisms have shown thatinfection with nef-deficient virus shows anattenuated course of infection and some

studies in humans have shown that nonprogression was associated with grossdeletions in the nef gene.

However, much of the research in the area todate has been based on observational or casestudies rather than rigorous, systematicscientific evaluation. This work by doctoralcandidate Ravindra Pushker set out todetermine in a substantially larger sample setif any association exists between diseaseprogression and particular amino aciddifferences or deletions within the nef gene.

On a per patient basis, there was no excess ofLTNP patients with one or more defective nefsequences when compared to progressors.While the high frequency of amino acidreplacement at particular residues is indicativeof rapid evolvement, permutation testingshowed that residues with more replacementsthan expected were not statistically significant.

The researchers conclude that current dataprovides no evidence that individual residues

of HIV nef are critical in determining the rateof disease progression. Professor DenisShields believes that searches for modifiers ofprogression rates should now focus on otherhost and viral factors. “Systematic evaluationof large quantities of data by bioinformaticscan be just as important in refutinghypotheses that are current in the literature, asit is in discovering unknown patterns”, he said.

This research was funded through ScienceFoundation Ireland and University CollegeDublin.

Reference:Meta-analysis to test the association of HIV-1 nef aminoacid differences and deletions with disease progression.Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields.Journal of Virology, Apr 2010 p3644-3653

GlycoExtractor advances glycan data manipulation

Glycomics needs the supporting frameworkof extensive, well-curated databases andflexible analytical tools. Currently, this fieldof study lacks the established,comprehensive and centralised datacollections, standards and informationreporting protocols that exist withingenomics and proteomics.

Researchers, Dr Natalia Artemenko and DrMatthew Campbell from the National Instituteof Bioprocessing Research & Training (NIBRT)led by Conway Fellow, Professor Pauline Ruddhave developed an open access, web-basedinterface that facilitates extraction, queryingand sharing of HPLC-glycan data generated inhigh throughput processes.

Glycosylation is the most common andstructurally diverse post-translationalmodification of proteins. More than half of allgene products have been shown to beglycosylated. With many specific glycans orglycoforms showing potential as cancerbiomarkers, there is an increasing need todevelop high throughput, highly sensitive androbust strategies that detail the glycome of

cells, tissues and fluids.

Commercial packages that support HPLCinstruments cannot facilitate the extraction oflarge quantities of data. In an effort to alleviatethis bottleneck within high-throughputglycomic projects, the NIBRT team havedeveloped a web-based tool that interfaceswith the Waters chromatography softwarepackage to improve and automate the exportof data to various file formats for subsequentanalysis. The modular architecture of the toolalso facilitates the manipulation of data fromother data management systems.

The NIBRT team are now working to integrateGlycoExtractor with the EUROCarbDBframework to provide a comprehensive high-throughput HPLC data analysis platform forthe storage and annotation of experimentaldata. The integration of next generationbioinformatic tools will further thedevelopment of unified approaches forhandling large scale glycomics data initiativeswith applications in biomarker discovery

This research was partially supported by

EUROCarbDB, a research infrastructure designstudy funded by the EU 6th FrameworkProgramme. Prospective users can access theGlycoExtractor tool onhttp://glycobase.nibrt.ie:8080/DemoGlycoExtractor/mainPage.ReferenceGlycoExtractor: A web-based interface for highthroughput processing of HPLC-Glycan dataNatalia V. Artemenko, Matthew P. Campbell, and PaulineM. Rudd Journal of Proteome Research, 2010, 9 (4), pp2037–2041

NIBRT researchers Dr Matthew Campbell and Dr NataliaArtemenko who developed GlycoExtractor

Zebrafish model gives insights into diabetic blindness

New research led by Conway Fellow DrBreandán Kennedy indicates that treatmentof diabetic blindness should look atprotecting the neurons responsible for colourvision in the eye and not just targeting theblood vessels as is currently the practice.

Nearly 2.5 million people worldwide are blinddue to diabetic retinopathy. This secondarycomplication of diabetes activates the growthof new leaky blood vessels in the eye and isresponsible for the death of photoreceptors,the neurons that send visual messages to ourbrain.

Until now, it was unclear if the changes tovessels and neurons occurred independently ofone other and which type of retinal neuron is

most likely to die as a result of the raisedglucose levels seen in diabetes.

Dr Kennedy and his team found that new bloodvessels and the neuronal cell death in diabeticretinopathy can arise independently of eachother. In addition, they identified that conephotoreceptor neurons, those involved incolour vision and used in daylight, are mostaffected by the high glucose levels.

The research team made their observationsusing a novel zebrafish model of diabetes,which resembles the early stages of diabeticretinopathy in humans. It is an excitingdevelopment for the group who now hope tofurther extend their research and establish amodel of late stage diabetic disease.

Commenting on the research, Dr Kennedysaid, “By establishing a robust model for earlyand late stage diabetic retinopathy, we wouldhope to better understand the progression ofthe disease and pave the way for identifyingnew drug targets for its successful treatment”.

The research was funded through ScienceFoundation Ireland and the Health ResearchBoard.

Reference:

Predominant cone photoreceptor dysfunction in ahyperglycaemic model of non-proliferative diabeticretinopathy. Yolanda Alvarez, Jenneth Chen, AlisonReynolds, Nore Waghorne, John J. O’Connor, BreandanKennedy. Disease Models & Mechanisms (2010)

May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3

A new look at the solid-liquid interface Interesting things happen at interfaces and where solids meet liquids is no exception. Understanding the complex phenomena taking place at the ‘solid-liquid’ interface could give important clues about how to build better medical devices and longer-lasting batteries, but to date it has been difficult to get a handle on how chemical ions in solution behave at this crucial juncture. Until now, that is.

A team led by UCD scientists has developed a new tool to build up a clearer picture of what is going on at this interface, and crucially, can do this on the nanoscale. The procedure, published in Nature Communications, stands to enable research in biological and materials science.

“The solid-liquid interface is the location of many important physical, biological and chemical processes,” explains researcher Liam Collins, who is completing a Ph.D. in the Nanoscale Function Group. “If you want to understand biosystems, diseases and novel biomaterials or processes in energy systems like batteries, you need to understand what happens at the solid-liquid interface.”

What happens on the atomic level at this interface can have an impact at a more visible or macroscopic level - the way the body functions, or how quickly a battery drains, for example - so techniques that can operate on atomic-length scales can improve our fundamental understanding of materials and devices, notes Collins, who works with Conway Fellow, Dr Brian Rodriguez.

Existing techniques, such as the atomic force microscope, already allow researchers to get a good ‘view’ of physical structures at the solid-liquid interface but not how ions behave at this interface, he explains: “So we set out to join structural informa-tion with electrochemical function.”

To get this multi-modal view, Collins worked with colleagues in UCD, Oak Ridge National Laboratory, USA and Taras Shevchenko Kiev National University, Ukraine to develop a technique called electrochemical force microscopy (EcFM).

The benefit of the new technique is that it allows researchers to get a clearer picture of what is going on at this key solid-liquid interface in situ rather than making

measurements in air and extrapolating toliquids, explains Collins.The team are now turning their attention to new materials, one being a form of ultra-thin carbon called graphene, which has applications in energy storage. “Probably the immediate improve-ment coming out of this EcFM technique will be a better understanding of energy systems such as double-layer capacitors and lithium ion batteries,” says Collins. “If we can understand the processes on the nanoscale here, it will in turn allow us to improve the efficiency and lifetime of devices.”

He also has an eye to a wide range of longer-term applications that could come from better understanding the relationship between structure and function in biologi-cal systems. “That may help us to develop in vivo batteries that harness biofuels, or to understand diseases like Alzheimer’s disease, at a fundamental level.”

(In conversation with journalist, Claire O’Connell for UCD Science showcase)

Irish biopharmaceutical developmentcompany, Sigmoid Pharma recently scoopedthe overall Innovation of the Year award atthe inaugural Irish Times All-IslandInnovation Awards. The life-science SME,founded by UCD pharmacology graduate, DrIvan Coulter, has actively collaborated withConway Fellow, Professor Cormac Taylorsince being granted a Science FoundationIreland industry research partnership awardin 2004.

The Irish Times award recognises the stellarinnovative performance of Sigmoid Pharma intheir application of research and development.The company has developed two new drugtechnologies, LEDDS™ and SmPill™, which notonly enhance the solubility and permeability ofthe drug but can deliver it to targeted locationsin the gastrointestinal tract, including thecolon.

The Sigmoid Pharma-Taylor collaboration isfacilitating the development of a newtherapeutic approach for the treatment ofinflammatory bowel disease (IBD) by bringingtogether the research methodology of theTaylor group with the proprietaryliquid/emulsion drug delivery system,LEDDS®, developed by Sigmoid Pharma.

Commenting on the award, Professor Taylorsaid, “We are delighted for Dr Coulter and histeam and indeed it reflects well on ourpartnership. A key driver of successfulscientific research in 2010 is meaningfulinteraction of academia with industry that

results in both academic outputs and theapplication of research toward clinical productdevelopment with indigenous companies.”

Commenting on the Taylor collaboration, DrCoulter said, “The collaboration with the Taylorlaboratory clearly demonstrates the potentialthat can be realised through focusedapplication of basic research. The developmentof a smart economy will depend on like-mindedcollaborative partners identifying opportunitiesand realising basic and applied researchsynergies. This collaboration, initiated througha SFI research supplement, highlights thepotential that innovative indigenous companiesworking with academia can realise.”

Taylor’s collaboration with Sigmoid Pharma hascertainly been successful by these metrics withthree co-authored publications to date in two ofthe highest ranking scientific journals in thefield, Gastroenterology and Proceeding of theNational Academy of Sciences, as well as thegeneration of proprietary innovative productsand the creation of high-skilled jobs.

More than 15,000 people in Ireland andmillions of people worldwide are living with thesymptoms IBD today. Current therapeuticoptions for this chronic debilitating disease arevery limited with surgery often being the onlyviable option. The Sigmoid product, currentlyin a phase II clinical study, uniquely enablesoral delivery of a powerful drug withoutcausing systemic side-effects.

Under normal conditions, the gastrointestinal

tract is lined with cells that block the contentsof the gut from leaking into the intestine. In anIBD patient, this barrier is broken and thecontents of the gut leak out into surroundingareas. The research team in UCD Conway useda model of IBD and, by applying a new class ofdrugs known as hydroxylase inhibitors, wereable to almost completely reverse thesymptoms of the disease.

“When we applied these new drugs to our IBDmodel, the gut was tricked into thinking that itwas being deprived of oxygen. This activatedprotective pathways, which in turn preventedthe death of the cells that line thegastrointestinal tract,” explained ProfessorTaylor. “Our pre-clinical trial data can nowinform the next phase Sigmoid Pharma productdevelopment pipeline”.

In addition to the product that is currently inphase II clinical studies, Sigmoid Pharma isdeveloping a LEDDS™-enabled formulation ofthe hydroxylase inhibitordimethyloxaloylglycine (DMOG) to bring abouteffective, safe and targeted delivery of thispotential therapeutic agent.

Conway collaborator scoops Irish Times Innovation Award

Conway researchers led by Dr. TaraMcMorrow and Professor Michael Ryan havesuccessfully secured €485,500 in funding aspart of an overall award to the SystemsBiology towards Novel Chronic KidneyDisease Diagnosis and Treatment (SysKid)consortium under the European Union FP7programme.

Syskid (www.SysKid.eu) was established tofurther our understanding of chronic kidney

disease (CKD) and improve patient treatment,with particular focus on CKD arising fromdiabetes and hypertension. The multi-disciplinary research consortium has 25partners (16 universities, 9 industry partners)from 15 countries and the project is due to runfor five years.

The UCD Conway team, including postdoctoralresearchers Dr. Craig Slattery and Dr. NataliaMartin, will utilise cell culture and animal

models to identify processes involved in earlyCKD progression and investigate novelstrategies for preventing and slowing theprogression of the disease. These studies willbe integrated with clinical and epidemiologicalstudies across the consortium using systemsbiology methodologies in order to develop newdiagnostic strategies and treatment options toprevent CKD development. [email protected] for details of a PhDposition currently available.

Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Meta-analysis by UCD researchers led byConway Fellow, Professor Denis Shields hasdetermined that there is no clear evidencethat particular defective viral sequences inthe HIV-1 nef gene or certain regions of theprotein play a significant role in diseaseprogression.

HIV-infected patients can be categorised onthe basis of the number of years it takes forthem to progress to AIDS. Some patientsmaintain stable CD4 lymphocyte counts anddo not go on to develop AIDS even after morethan 10 years of infection.

Scientists are curious as to why these long-term, non- progressor (LTNP) patients do notdevelop AIDS. This may reflect differences inthe host, viral genetics or environmentalfactors that could potentially be exploited forthe treatment of the disease.

Studies in model organisms have shown thatinfection with nef-deficient virus shows anattenuated course of infection and some

studies in humans have shown that nonprogression was associated with grossdeletions in the nef gene.

However, much of the research in the area todate has been based on observational or casestudies rather than rigorous, systematicscientific evaluation. This work by doctoralcandidate Ravindra Pushker set out todetermine in a substantially larger sample setif any association exists between diseaseprogression and particular amino aciddifferences or deletions within the nef gene.

On a per patient basis, there was no excess ofLTNP patients with one or more defective nefsequences when compared to progressors.While the high frequency of amino acidreplacement at particular residues is indicativeof rapid evolvement, permutation testingshowed that residues with more replacementsthan expected were not statistically significant.

The researchers conclude that current dataprovides no evidence that individual residues

of HIV nef are critical in determining the rateof disease progression. Professor DenisShields believes that searches for modifiers ofprogression rates should now focus on otherhost and viral factors. “Systematic evaluationof large quantities of data by bioinformaticscan be just as important in refutinghypotheses that are current in the literature, asit is in discovering unknown patterns”, he said.

This research was funded through ScienceFoundation Ireland and University CollegeDublin.

Reference:Meta-analysis to test the association of HIV-1 nef aminoacid differences and deletions with disease progression.Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields.Journal of Virology, Apr 2010 p3644-3653

GlycoExtractor advances glycan data manipulation

Glycomics needs the supporting frameworkof extensive, well-curated databases andflexible analytical tools. Currently, this fieldof study lacks the established,comprehensive and centralised datacollections, standards and informationreporting protocols that exist withingenomics and proteomics.

Researchers, Dr Natalia Artemenko and DrMatthew Campbell from the National Instituteof Bioprocessing Research & Training (NIBRT)led by Conway Fellow, Professor Pauline Ruddhave developed an open access, web-basedinterface that facilitates extraction, queryingand sharing of HPLC-glycan data generated inhigh throughput processes.

Glycosylation is the most common andstructurally diverse post-translationalmodification of proteins. More than half of allgene products have been shown to beglycosylated. With many specific glycans orglycoforms showing potential as cancerbiomarkers, there is an increasing need todevelop high throughput, highly sensitive androbust strategies that detail the glycome of

cells, tissues and fluids.

Commercial packages that support HPLCinstruments cannot facilitate the extraction oflarge quantities of data. In an effort to alleviatethis bottleneck within high-throughputglycomic projects, the NIBRT team havedeveloped a web-based tool that interfaceswith the Waters chromatography softwarepackage to improve and automate the exportof data to various file formats for subsequentanalysis. The modular architecture of the toolalso facilitates the manipulation of data fromother data management systems.

The NIBRT team are now working to integrateGlycoExtractor with the EUROCarbDBframework to provide a comprehensive high-throughput HPLC data analysis platform forthe storage and annotation of experimentaldata. The integration of next generationbioinformatic tools will further thedevelopment of unified approaches forhandling large scale glycomics data initiativeswith applications in biomarker discovery

This research was partially supported by

EUROCarbDB, a research infrastructure designstudy funded by the EU 6th FrameworkProgramme. Prospective users can access theGlycoExtractor tool onhttp://glycobase.nibrt.ie:8080/DemoGlycoExtractor/mainPage.ReferenceGlycoExtractor: A web-based interface for highthroughput processing of HPLC-Glycan dataNatalia V. Artemenko, Matthew P. Campbell, and PaulineM. Rudd Journal of Proteome Research, 2010, 9 (4), pp2037–2041

NIBRT researchers Dr Matthew Campbell and Dr NataliaArtemenko who developed GlycoExtractor

Zebrafish model gives insights into diabetic blindness

New research led by Conway Fellow DrBreandán Kennedy indicates that treatmentof diabetic blindness should look atprotecting the neurons responsible for colourvision in the eye and not just targeting theblood vessels as is currently the practice.

Nearly 2.5 million people worldwide are blinddue to diabetic retinopathy. This secondarycomplication of diabetes activates the growthof new leaky blood vessels in the eye and isresponsible for the death of photoreceptors,the neurons that send visual messages to ourbrain.

Until now, it was unclear if the changes tovessels and neurons occurred independently ofone other and which type of retinal neuron is

most likely to die as a result of the raisedglucose levels seen in diabetes.

Dr Kennedy and his team found that new bloodvessels and the neuronal cell death in diabeticretinopathy can arise independently of eachother. In addition, they identified that conephotoreceptor neurons, those involved incolour vision and used in daylight, are mostaffected by the high glucose levels.

The research team made their observationsusing a novel zebrafish model of diabetes,which resembles the early stages of diabeticretinopathy in humans. It is an excitingdevelopment for the group who now hope tofurther extend their research and establish amodel of late stage diabetic disease.

Commenting on the research, Dr Kennedysaid, “By establishing a robust model for earlyand late stage diabetic retinopathy, we wouldhope to better understand the progression ofthe disease and pave the way for identifyingnew drug targets for its successful treatment”.

The research was funded through ScienceFoundation Ireland and the Health ResearchBoard.

Reference:

Predominant cone photoreceptor dysfunction in ahyperglycaemic model of non-proliferative diabeticretinopathy. Yolanda Alvarez, Jenneth Chen, AlisonReynolds, Nore Waghorne, John J. O’Connor, BreandanKennedy. Disease Models & Mechanisms (2010)

May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3

Director’s MessageWelcome!

Under the latest round of the Science Foundation Ireland Investigator Programme, seven research projects led by UCD and one partnered with Teagasc will receive funding. This is the joint highest number of research projects from any one institution to receive funding under this round and five of these projects will be led by Conway Fellows. Congratulations to them and to the many other Fellows

who continue to secure funding in an increasingly competitive and challenging environment.

I was delighted to welcome UCD President, Professor Andrew Deeks to the Institute at the beginning of May and for Conway Fellows to have the opportunity to highlight their contributions to research excellence, innovation and outstanding scholarship in the University.

Congratulations to Conway researchers and alumni who have been actively organising and participating in science engagements activities such as Pint of Science, Soapbox Science, and Engage. Your passion for research and willingness to reach audiences outside of your peers will help to embed science firmly within society.

Professor Walter Kolch Director

Issu

e 22

, Sum

mer

201

4

Irish biopharmaceutical developmentcompany, Sigmoid Pharma recently scoopedthe overall Innovation of the Year award atthe inaugural Irish Times All-IslandInnovation Awards. The life-science SME,founded by UCD pharmacology graduate, DrIvan Coulter, has actively collaborated withConway Fellow, Professor Cormac Taylorsince being granted a Science FoundationIreland industry research partnership awardin 2004.

The Irish Times award recognises the stellarinnovative performance of Sigmoid Pharma intheir application of research and development.The company has developed two new drugtechnologies, LEDDS™ and SmPill™, which notonly enhance the solubility and permeability ofthe drug but can deliver it to targeted locationsin the gastrointestinal tract, including thecolon.

The Sigmoid Pharma-Taylor collaboration isfacilitating the development of a newtherapeutic approach for the treatment ofinflammatory bowel disease (IBD) by bringingtogether the research methodology of theTaylor group with the proprietaryliquid/emulsion drug delivery system,LEDDS®, developed by Sigmoid Pharma.

Commenting on the award, Professor Taylorsaid, “We are delighted for Dr Coulter and histeam and indeed it reflects well on ourpartnership. A key driver of successfulscientific research in 2010 is meaningfulinteraction of academia with industry that

results in both academic outputs and theapplication of research toward clinical productdevelopment with indigenous companies.”

Commenting on the Taylor collaboration, DrCoulter said, “The collaboration with the Taylorlaboratory clearly demonstrates the potentialthat can be realised through focusedapplication of basic research. The developmentof a smart economy will depend on like-mindedcollaborative partners identifying opportunitiesand realising basic and applied researchsynergies. This collaboration, initiated througha SFI research supplement, highlights thepotential that innovative indigenous companiesworking with academia can realise.”

Taylor’s collaboration with Sigmoid Pharma hascertainly been successful by these metrics withthree co-authored publications to date in two ofthe highest ranking scientific journals in thefield, Gastroenterology and Proceeding of theNational Academy of Sciences, as well as thegeneration of proprietary innovative productsand the creation of high-skilled jobs.

More than 15,000 people in Ireland andmillions of people worldwide are living with thesymptoms IBD today. Current therapeuticoptions for this chronic debilitating disease arevery limited with surgery often being the onlyviable option. The Sigmoid product, currentlyin a phase II clinical study, uniquely enablesoral delivery of a powerful drug withoutcausing systemic side-effects.

Under normal conditions, the gastrointestinal

tract is lined with cells that block the contentsof the gut from leaking into the intestine. In anIBD patient, this barrier is broken and thecontents of the gut leak out into surroundingareas. The research team in UCD Conway useda model of IBD and, by applying a new class ofdrugs known as hydroxylase inhibitors, wereable to almost completely reverse thesymptoms of the disease.

“When we applied these new drugs to our IBDmodel, the gut was tricked into thinking that itwas being deprived of oxygen. This activatedprotective pathways, which in turn preventedthe death of the cells that line thegastrointestinal tract,” explained ProfessorTaylor. “Our pre-clinical trial data can nowinform the next phase Sigmoid Pharma productdevelopment pipeline”.

In addition to the product that is currently inphase II clinical studies, Sigmoid Pharma isdeveloping a LEDDS™-enabled formulation ofthe hydroxylase inhibitordimethyloxaloylglycine (DMOG) to bring abouteffective, safe and targeted delivery of thispotential therapeutic agent.

Conway collaborator scoops Irish Times Innovation Award

Conway researchers led by Dr. TaraMcMorrow and Professor Michael Ryan havesuccessfully secured €485,500 in funding aspart of an overall award to the SystemsBiology towards Novel Chronic KidneyDisease Diagnosis and Treatment (SysKid)consortium under the European Union FP7programme.

Syskid (www.SysKid.eu) was established tofurther our understanding of chronic kidney

disease (CKD) and improve patient treatment,with particular focus on CKD arising fromdiabetes and hypertension. The multi-disciplinary research consortium has 25partners (16 universities, 9 industry partners)from 15 countries and the project is due to runfor five years.

The UCD Conway team, including postdoctoralresearchers Dr. Craig Slattery and Dr. NataliaMartin, will utilise cell culture and animal

models to identify processes involved in earlyCKD progression and investigate novelstrategies for preventing and slowing theprogression of the disease. These studies willbe integrated with clinical and epidemiologicalstudies across the consortium using systemsbiology methodologies in order to develop newdiagnostic strategies and treatment options toprevent CKD development. [email protected] for details of a PhDposition currently available.

Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Meta-analysis by UCD researchers led byConway Fellow, Professor Denis Shields hasdetermined that there is no clear evidencethat particular defective viral sequences inthe HIV-1 nef gene or certain regions of theprotein play a significant role in diseaseprogression.

HIV-infected patients can be categorised onthe basis of the number of years it takes forthem to progress to AIDS. Some patientsmaintain stable CD4 lymphocyte counts anddo not go on to develop AIDS even after morethan 10 years of infection.

Scientists are curious as to why these long-term, non- progressor (LTNP) patients do notdevelop AIDS. This may reflect differences inthe host, viral genetics or environmentalfactors that could potentially be exploited forthe treatment of the disease.

Studies in model organisms have shown thatinfection with nef-deficient virus shows anattenuated course of infection and some

studies in humans have shown that nonprogression was associated with grossdeletions in the nef gene.

However, much of the research in the area todate has been based on observational or casestudies rather than rigorous, systematicscientific evaluation. This work by doctoralcandidate Ravindra Pushker set out todetermine in a substantially larger sample setif any association exists between diseaseprogression and particular amino aciddifferences or deletions within the nef gene.

On a per patient basis, there was no excess ofLTNP patients with one or more defective nefsequences when compared to progressors.While the high frequency of amino acidreplacement at particular residues is indicativeof rapid evolvement, permutation testingshowed that residues with more replacementsthan expected were not statistically significant.

The researchers conclude that current dataprovides no evidence that individual residues

of HIV nef are critical in determining the rateof disease progression. Professor DenisShields believes that searches for modifiers ofprogression rates should now focus on otherhost and viral factors. “Systematic evaluationof large quantities of data by bioinformaticscan be just as important in refutinghypotheses that are current in the literature, asit is in discovering unknown patterns”, he said.

This research was funded through ScienceFoundation Ireland and University CollegeDublin.

Reference:Meta-analysis to test the association of HIV-1 nef aminoacid differences and deletions with disease progression.Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields.Journal of Virology, Apr 2010 p3644-3653

GlycoExtractor advances glycan data manipulation

Glycomics needs the supporting frameworkof extensive, well-curated databases andflexible analytical tools. Currently, this fieldof study lacks the established,comprehensive and centralised datacollections, standards and informationreporting protocols that exist withingenomics and proteomics.

Researchers, Dr Natalia Artemenko and DrMatthew Campbell from the National Instituteof Bioprocessing Research & Training (NIBRT)led by Conway Fellow, Professor Pauline Ruddhave developed an open access, web-basedinterface that facilitates extraction, queryingand sharing of HPLC-glycan data generated inhigh throughput processes.

Glycosylation is the most common andstructurally diverse post-translationalmodification of proteins. More than half of allgene products have been shown to beglycosylated. With many specific glycans orglycoforms showing potential as cancerbiomarkers, there is an increasing need todevelop high throughput, highly sensitive androbust strategies that detail the glycome of

cells, tissues and fluids.

Commercial packages that support HPLCinstruments cannot facilitate the extraction oflarge quantities of data. In an effort to alleviatethis bottleneck within high-throughputglycomic projects, the NIBRT team havedeveloped a web-based tool that interfaceswith the Waters chromatography softwarepackage to improve and automate the exportof data to various file formats for subsequentanalysis. The modular architecture of the toolalso facilitates the manipulation of data fromother data management systems.

The NIBRT team are now working to integrateGlycoExtractor with the EUROCarbDBframework to provide a comprehensive high-throughput HPLC data analysis platform forthe storage and annotation of experimentaldata. The integration of next generationbioinformatic tools will further thedevelopment of unified approaches forhandling large scale glycomics data initiativeswith applications in biomarker discovery

This research was partially supported by

EUROCarbDB, a research infrastructure designstudy funded by the EU 6th FrameworkProgramme. Prospective users can access theGlycoExtractor tool onhttp://glycobase.nibrt.ie:8080/DemoGlycoExtractor/mainPage.ReferenceGlycoExtractor: A web-based interface for highthroughput processing of HPLC-Glycan dataNatalia V. Artemenko, Matthew P. Campbell, and PaulineM. Rudd Journal of Proteome Research, 2010, 9 (4), pp2037–2041

NIBRT researchers Dr Matthew Campbell and Dr NataliaArtemenko who developed GlycoExtractor

Zebrafish model gives insights into diabetic blindness

New research led by Conway Fellow DrBreandán Kennedy indicates that treatmentof diabetic blindness should look atprotecting the neurons responsible for colourvision in the eye and not just targeting theblood vessels as is currently the practice.

Nearly 2.5 million people worldwide are blinddue to diabetic retinopathy. This secondarycomplication of diabetes activates the growthof new leaky blood vessels in the eye and isresponsible for the death of photoreceptors,the neurons that send visual messages to ourbrain.

Until now, it was unclear if the changes tovessels and neurons occurred independently ofone other and which type of retinal neuron is

most likely to die as a result of the raisedglucose levels seen in diabetes.

Dr Kennedy and his team found that new bloodvessels and the neuronal cell death in diabeticretinopathy can arise independently of eachother. In addition, they identified that conephotoreceptor neurons, those involved incolour vision and used in daylight, are mostaffected by the high glucose levels.

The research team made their observationsusing a novel zebrafish model of diabetes,which resembles the early stages of diabeticretinopathy in humans. It is an excitingdevelopment for the group who now hope tofurther extend their research and establish amodel of late stage diabetic disease.

Commenting on the research, Dr Kennedysaid, “By establishing a robust model for earlyand late stage diabetic retinopathy, we wouldhope to better understand the progression ofthe disease and pave the way for identifyingnew drug targets for its successful treatment”.

The research was funded through ScienceFoundation Ireland and the Health ResearchBoard.

Reference:

Predominant cone photoreceptor dysfunction in ahyperglycaemic model of non-proliferative diabeticretinopathy. Yolanda Alvarez, Jenneth Chen, AlisonReynolds, Nore Waghorne, John J. O’Connor, BreandanKennedy. Disease Models & Mechanisms (2010)

May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3

From a patient perspective, tablets are preferable to injections when it comes to taking medication. The pharmaceutical company, Unigene (NJ, USA) have designed a proprietary tablet formulation of calcitonin, an anti-osteoporosis drug that is usually injected.

UCD researchers led by Conway Fellow, Prof David Brayden have revealed the role played by one ingredient in this new tablet, an additive called citric acid, in enabling oral delivery of calcitonin.

Normally, calcitonin is broken down in the gut as it is a small protein (peptide) and unable to permeate the gut wall

to reach the blood. In collaboration with Novo-Nordisk and Copenhagen University, the team showed that citric acid in the tablet acted only to prevent breakdown and not to increase permeation across the epithelium of the gut.

The finding means that there was no permeation enhancer in the calcitonin tablet and that the data achieved in phase III clinical trials by Unigene arose simply from preserving calcitonin intact using agents approved in other products and presenting it to the gut wall in the small intestine region.

Prof David Brayden explained, “We worked out that the concentration of

the peptide reaching the blood from oral administration was no more than 2%, which is still enough to compete with nasal competitor products for such a potent and exceptional agent.

However, in future, less potent peptide products would need enhancers to get higher percentages of peptide to the blood and this has toxicological implications.”

Enabling oral drug delivery

In BriefIrish biopharmaceutical developmentcompany, Sigmoid Pharma recently scoopedthe overall Innovation of the Year award atthe inaugural Irish Times All-IslandInnovation Awards. The life-science SME,founded by UCD pharmacology graduate, DrIvan Coulter, has actively collaborated withConway Fellow, Professor Cormac Taylorsince being granted a Science FoundationIreland industry research partnership awardin 2004.

The Irish Times award recognises the stellarinnovative performance of Sigmoid Pharma intheir application of research and development.The company has developed two new drugtechnologies, LEDDS™ and SmPill™, which notonly enhance the solubility and permeability ofthe drug but can deliver it to targeted locationsin the gastrointestinal tract, including thecolon.

The Sigmoid Pharma-Taylor collaboration isfacilitating the development of a newtherapeutic approach for the treatment ofinflammatory bowel disease (IBD) by bringingtogether the research methodology of theTaylor group with the proprietaryliquid/emulsion drug delivery system,LEDDS®, developed by Sigmoid Pharma.

Commenting on the award, Professor Taylorsaid, “We are delighted for Dr Coulter and histeam and indeed it reflects well on ourpartnership. A key driver of successfulscientific research in 2010 is meaningfulinteraction of academia with industry that

results in both academic outputs and theapplication of research toward clinical productdevelopment with indigenous companies.”

Commenting on the Taylor collaboration, DrCoulter said, “The collaboration with the Taylorlaboratory clearly demonstrates the potentialthat can be realised through focusedapplication of basic research. The developmentof a smart economy will depend on like-mindedcollaborative partners identifying opportunitiesand realising basic and applied researchsynergies. This collaboration, initiated througha SFI research supplement, highlights thepotential that innovative indigenous companiesworking with academia can realise.”

Taylor’s collaboration with Sigmoid Pharma hascertainly been successful by these metrics withthree co-authored publications to date in two ofthe highest ranking scientific journals in thefield, Gastroenterology and Proceeding of theNational Academy of Sciences, as well as thegeneration of proprietary innovative productsand the creation of high-skilled jobs.

More than 15,000 people in Ireland andmillions of people worldwide are living with thesymptoms IBD today. Current therapeuticoptions for this chronic debilitating disease arevery limited with surgery often being the onlyviable option. The Sigmoid product, currentlyin a phase II clinical study, uniquely enablesoral delivery of a powerful drug withoutcausing systemic side-effects.

Under normal conditions, the gastrointestinal

tract is lined with cells that block the contentsof the gut from leaking into the intestine. In anIBD patient, this barrier is broken and thecontents of the gut leak out into surroundingareas. The research team in UCD Conway useda model of IBD and, by applying a new class ofdrugs known as hydroxylase inhibitors, wereable to almost completely reverse thesymptoms of the disease.

“When we applied these new drugs to our IBDmodel, the gut was tricked into thinking that itwas being deprived of oxygen. This activatedprotective pathways, which in turn preventedthe death of the cells that line thegastrointestinal tract,” explained ProfessorTaylor. “Our pre-clinical trial data can nowinform the next phase Sigmoid Pharma productdevelopment pipeline”.

In addition to the product that is currently inphase II clinical studies, Sigmoid Pharma isdeveloping a LEDDS™-enabled formulation ofthe hydroxylase inhibitordimethyloxaloylglycine (DMOG) to bring abouteffective, safe and targeted delivery of thispotential therapeutic agent.

Conway collaborator scoops Irish Times Innovation Award

Conway researchers led by Dr. TaraMcMorrow and Professor Michael Ryan havesuccessfully secured €485,500 in funding aspart of an overall award to the SystemsBiology towards Novel Chronic KidneyDisease Diagnosis and Treatment (SysKid)consortium under the European Union FP7programme.

Syskid (www.SysKid.eu) was established tofurther our understanding of chronic kidney

disease (CKD) and improve patient treatment,with particular focus on CKD arising fromdiabetes and hypertension. The multi-disciplinary research consortium has 25partners (16 universities, 9 industry partners)from 15 countries and the project is due to runfor five years.

The UCD Conway team, including postdoctoralresearchers Dr. Craig Slattery and Dr. NataliaMartin, will utilise cell culture and animal

models to identify processes involved in earlyCKD progression and investigate novelstrategies for preventing and slowing theprogression of the disease. These studies willbe integrated with clinical and epidemiologicalstudies across the consortium using systemsbiology methodologies in order to develop newdiagnostic strategies and treatment options toprevent CKD development. [email protected] for details of a PhDposition currently available.

Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Meta-analysis by UCD researchers led byConway Fellow, Professor Denis Shields hasdetermined that there is no clear evidencethat particular defective viral sequences inthe HIV-1 nef gene or certain regions of theprotein play a significant role in diseaseprogression.

HIV-infected patients can be categorised onthe basis of the number of years it takes forthem to progress to AIDS. Some patientsmaintain stable CD4 lymphocyte counts anddo not go on to develop AIDS even after morethan 10 years of infection.

Scientists are curious as to why these long-term, non- progressor (LTNP) patients do notdevelop AIDS. This may reflect differences inthe host, viral genetics or environmentalfactors that could potentially be exploited forthe treatment of the disease.

Studies in model organisms have shown thatinfection with nef-deficient virus shows anattenuated course of infection and some

studies in humans have shown that nonprogression was associated with grossdeletions in the nef gene.

However, much of the research in the area todate has been based on observational or casestudies rather than rigorous, systematicscientific evaluation. This work by doctoralcandidate Ravindra Pushker set out todetermine in a substantially larger sample setif any association exists between diseaseprogression and particular amino aciddifferences or deletions within the nef gene.

On a per patient basis, there was no excess ofLTNP patients with one or more defective nefsequences when compared to progressors.While the high frequency of amino acidreplacement at particular residues is indicativeof rapid evolvement, permutation testingshowed that residues with more replacementsthan expected were not statistically significant.

The researchers conclude that current dataprovides no evidence that individual residues

of HIV nef are critical in determining the rateof disease progression. Professor DenisShields believes that searches for modifiers ofprogression rates should now focus on otherhost and viral factors. “Systematic evaluationof large quantities of data by bioinformaticscan be just as important in refutinghypotheses that are current in the literature, asit is in discovering unknown patterns”, he said.

This research was funded through ScienceFoundation Ireland and University CollegeDublin.

Reference:Meta-analysis to test the association of HIV-1 nef aminoacid differences and deletions with disease progression.Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields.Journal of Virology, Apr 2010 p3644-3653

GlycoExtractor advances glycan data manipulation

Glycomics needs the supporting frameworkof extensive, well-curated databases andflexible analytical tools. Currently, this fieldof study lacks the established,comprehensive and centralised datacollections, standards and informationreporting protocols that exist withingenomics and proteomics.

Researchers, Dr Natalia Artemenko and DrMatthew Campbell from the National Instituteof Bioprocessing Research & Training (NIBRT)led by Conway Fellow, Professor Pauline Ruddhave developed an open access, web-basedinterface that facilitates extraction, queryingand sharing of HPLC-glycan data generated inhigh throughput processes.

Glycosylation is the most common andstructurally diverse post-translationalmodification of proteins. More than half of allgene products have been shown to beglycosylated. With many specific glycans orglycoforms showing potential as cancerbiomarkers, there is an increasing need todevelop high throughput, highly sensitive androbust strategies that detail the glycome of

cells, tissues and fluids.

Commercial packages that support HPLCinstruments cannot facilitate the extraction oflarge quantities of data. In an effort to alleviatethis bottleneck within high-throughputglycomic projects, the NIBRT team havedeveloped a web-based tool that interfaceswith the Waters chromatography softwarepackage to improve and automate the exportof data to various file formats for subsequentanalysis. The modular architecture of the toolalso facilitates the manipulation of data fromother data management systems.

The NIBRT team are now working to integrateGlycoExtractor with the EUROCarbDBframework to provide a comprehensive high-throughput HPLC data analysis platform forthe storage and annotation of experimentaldata. The integration of next generationbioinformatic tools will further thedevelopment of unified approaches forhandling large scale glycomics data initiativeswith applications in biomarker discovery

This research was partially supported by

EUROCarbDB, a research infrastructure designstudy funded by the EU 6th FrameworkProgramme. Prospective users can access theGlycoExtractor tool onhttp://glycobase.nibrt.ie:8080/DemoGlycoExtractor/mainPage.ReferenceGlycoExtractor: A web-based interface for highthroughput processing of HPLC-Glycan dataNatalia V. Artemenko, Matthew P. Campbell, and PaulineM. Rudd Journal of Proteome Research, 2010, 9 (4), pp2037–2041

NIBRT researchers Dr Matthew Campbell and Dr NataliaArtemenko who developed GlycoExtractor

Zebrafish model gives insights into diabetic blindness

New research led by Conway Fellow DrBreandán Kennedy indicates that treatmentof diabetic blindness should look atprotecting the neurons responsible for colourvision in the eye and not just targeting theblood vessels as is currently the practice.

Nearly 2.5 million people worldwide are blinddue to diabetic retinopathy. This secondarycomplication of diabetes activates the growthof new leaky blood vessels in the eye and isresponsible for the death of photoreceptors,the neurons that send visual messages to ourbrain.

Until now, it was unclear if the changes tovessels and neurons occurred independently ofone other and which type of retinal neuron is

most likely to die as a result of the raisedglucose levels seen in diabetes.

Dr Kennedy and his team found that new bloodvessels and the neuronal cell death in diabeticretinopathy can arise independently of eachother. In addition, they identified that conephotoreceptor neurons, those involved incolour vision and used in daylight, are mostaffected by the high glucose levels.

The research team made their observationsusing a novel zebrafish model of diabetes,which resembles the early stages of diabeticretinopathy in humans. It is an excitingdevelopment for the group who now hope tofurther extend their research and establish amodel of late stage diabetic disease.

Commenting on the research, Dr Kennedysaid, “By establishing a robust model for earlyand late stage diabetic retinopathy, we wouldhope to better understand the progression ofthe disease and pave the way for identifyingnew drug targets for its successful treatment”.

The research was funded through ScienceFoundation Ireland and the Health ResearchBoard.

Reference:

Predominant cone photoreceptor dysfunction in ahyperglycaemic model of non-proliferative diabeticretinopathy. Yolanda Alvarez, Jenneth Chen, AlisonReynolds, Nore Waghorne, John J. O’Connor, BreandanKennedy. Disease Models & Mechanisms (2010)

May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3

Reference Welling SH et al. The role of citric acid in oral peptide and protein formulations: Relationship between calcium chelation and proteolysis inhibition. Eur J Pharm Biopharm. 2014 Apr;86(3):544-51. doi: 10.1016/j.ejpb.2013.12.017.

All living organisms require enzymes that are biological catalysts. These catalysts speed up biological reactions so life is possible. Under biological conditions, it would take about 7,000 years for just half of peptide bonds in a protein to be digested. Fortunately, proteolytic enzymes such as chymotrypsin allow us to digest proteins in hours rather than years.

A recent publication from the group led by Conway Fellow, Prof J.P.G Malthouse examines how chymotrypsin can speed up reactions by a factor of one thousand million. The team found that one of the mechanisms chymotrypsin uses is to

increase the reactivity of its active site hydroxyl group by ~100,000 times.

Reproductive performance of cows affects the efficiency of milk and beef production because of its influence on the calving to first service interval, subsequent calving pattern, length of lactation and culling rate, and culling rates for failure to conceive.

A recent publication from Conway Fellow, Prof Mark Crowe updates earlier reviews on the topic of reproductive efficiency in dairy and beef cows and focuses on factors contributing to resumption of ovulation and affecting uterine health in postpartum dairy and beef cows.

In PicturesIrish biopharmaceutical developmentcompany, Sigmoid Pharma recently scoopedthe overall Innovation of the Year award atthe inaugural Irish Times All-IslandInnovation Awards. The life-science SME,founded by UCD pharmacology graduate, DrIvan Coulter, has actively collaborated withConway Fellow, Professor Cormac Taylorsince being granted a Science FoundationIreland industry research partnership awardin 2004.

The Irish Times award recognises the stellarinnovative performance of Sigmoid Pharma intheir application of research and development.The company has developed two new drugtechnologies, LEDDS™ and SmPill™, which notonly enhance the solubility and permeability ofthe drug but can deliver it to targeted locationsin the gastrointestinal tract, including thecolon.

The Sigmoid Pharma-Taylor collaboration isfacilitating the development of a newtherapeutic approach for the treatment ofinflammatory bowel disease (IBD) by bringingtogether the research methodology of theTaylor group with the proprietaryliquid/emulsion drug delivery system,LEDDS®, developed by Sigmoid Pharma.

Commenting on the award, Professor Taylorsaid, “We are delighted for Dr Coulter and histeam and indeed it reflects well on ourpartnership. A key driver of successfulscientific research in 2010 is meaningfulinteraction of academia with industry that

results in both academic outputs and theapplication of research toward clinical productdevelopment with indigenous companies.”

Commenting on the Taylor collaboration, DrCoulter said, “The collaboration with the Taylorlaboratory clearly demonstrates the potentialthat can be realised through focusedapplication of basic research. The developmentof a smart economy will depend on like-mindedcollaborative partners identifying opportunitiesand realising basic and applied researchsynergies. This collaboration, initiated througha SFI research supplement, highlights thepotential that innovative indigenous companiesworking with academia can realise.”

Taylor’s collaboration with Sigmoid Pharma hascertainly been successful by these metrics withthree co-authored publications to date in two ofthe highest ranking scientific journals in thefield, Gastroenterology and Proceeding of theNational Academy of Sciences, as well as thegeneration of proprietary innovative productsand the creation of high-skilled jobs.

More than 15,000 people in Ireland andmillions of people worldwide are living with thesymptoms IBD today. Current therapeuticoptions for this chronic debilitating disease arevery limited with surgery often being the onlyviable option. The Sigmoid product, currentlyin a phase II clinical study, uniquely enablesoral delivery of a powerful drug withoutcausing systemic side-effects.

Under normal conditions, the gastrointestinal

tract is lined with cells that block the contentsof the gut from leaking into the intestine. In anIBD patient, this barrier is broken and thecontents of the gut leak out into surroundingareas. The research team in UCD Conway useda model of IBD and, by applying a new class ofdrugs known as hydroxylase inhibitors, wereable to almost completely reverse thesymptoms of the disease.

“When we applied these new drugs to our IBDmodel, the gut was tricked into thinking that itwas being deprived of oxygen. This activatedprotective pathways, which in turn preventedthe death of the cells that line thegastrointestinal tract,” explained ProfessorTaylor. “Our pre-clinical trial data can nowinform the next phase Sigmoid Pharma productdevelopment pipeline”.

In addition to the product that is currently inphase II clinical studies, Sigmoid Pharma isdeveloping a LEDDS™-enabled formulation ofthe hydroxylase inhibitordimethyloxaloylglycine (DMOG) to bring abouteffective, safe and targeted delivery of thispotential therapeutic agent.

Conway collaborator scoops Irish Times Innovation Award

Conway researchers led by Dr. TaraMcMorrow and Professor Michael Ryan havesuccessfully secured €485,500 in funding aspart of an overall award to the SystemsBiology towards Novel Chronic KidneyDisease Diagnosis and Treatment (SysKid)consortium under the European Union FP7programme.

Syskid (www.SysKid.eu) was established tofurther our understanding of chronic kidney

disease (CKD) and improve patient treatment,with particular focus on CKD arising fromdiabetes and hypertension. The multi-disciplinary research consortium has 25partners (16 universities, 9 industry partners)from 15 countries and the project is due to runfor five years.

The UCD Conway team, including postdoctoralresearchers Dr. Craig Slattery and Dr. NataliaMartin, will utilise cell culture and animal

models to identify processes involved in earlyCKD progression and investigate novelstrategies for preventing and slowing theprogression of the disease. These studies willbe integrated with clinical and epidemiologicalstudies across the consortium using systemsbiology methodologies in order to develop newdiagnostic strategies and treatment options toprevent CKD development. [email protected] for details of a PhDposition currently available.

Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Meta-analysis by UCD researchers led byConway Fellow, Professor Denis Shields hasdetermined that there is no clear evidencethat particular defective viral sequences inthe HIV-1 nef gene or certain regions of theprotein play a significant role in diseaseprogression.

HIV-infected patients can be categorised onthe basis of the number of years it takes forthem to progress to AIDS. Some patientsmaintain stable CD4 lymphocyte counts anddo not go on to develop AIDS even after morethan 10 years of infection.

Scientists are curious as to why these long-term, non- progressor (LTNP) patients do notdevelop AIDS. This may reflect differences inthe host, viral genetics or environmentalfactors that could potentially be exploited forthe treatment of the disease.

Studies in model organisms have shown thatinfection with nef-deficient virus shows anattenuated course of infection and some

studies in humans have shown that nonprogression was associated with grossdeletions in the nef gene.

However, much of the research in the area todate has been based on observational or casestudies rather than rigorous, systematicscientific evaluation. This work by doctoralcandidate Ravindra Pushker set out todetermine in a substantially larger sample setif any association exists between diseaseprogression and particular amino aciddifferences or deletions within the nef gene.

On a per patient basis, there was no excess ofLTNP patients with one or more defective nefsequences when compared to progressors.While the high frequency of amino acidreplacement at particular residues is indicativeof rapid evolvement, permutation testingshowed that residues with more replacementsthan expected were not statistically significant.

The researchers conclude that current dataprovides no evidence that individual residues

of HIV nef are critical in determining the rateof disease progression. Professor DenisShields believes that searches for modifiers ofprogression rates should now focus on otherhost and viral factors. “Systematic evaluationof large quantities of data by bioinformaticscan be just as important in refutinghypotheses that are current in the literature, asit is in discovering unknown patterns”, he said.

This research was funded through ScienceFoundation Ireland and University CollegeDublin.

Reference:Meta-analysis to test the association of HIV-1 nef aminoacid differences and deletions with disease progression.Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields.Journal of Virology, Apr 2010 p3644-3653

GlycoExtractor advances glycan data manipulation

Glycomics needs the supporting frameworkof extensive, well-curated databases andflexible analytical tools. Currently, this fieldof study lacks the established,comprehensive and centralised datacollections, standards and informationreporting protocols that exist withingenomics and proteomics.

Researchers, Dr Natalia Artemenko and DrMatthew Campbell from the National Instituteof Bioprocessing Research & Training (NIBRT)led by Conway Fellow, Professor Pauline Ruddhave developed an open access, web-basedinterface that facilitates extraction, queryingand sharing of HPLC-glycan data generated inhigh throughput processes.

Glycosylation is the most common andstructurally diverse post-translationalmodification of proteins. More than half of allgene products have been shown to beglycosylated. With many specific glycans orglycoforms showing potential as cancerbiomarkers, there is an increasing need todevelop high throughput, highly sensitive androbust strategies that detail the glycome of

cells, tissues and fluids.

Commercial packages that support HPLCinstruments cannot facilitate the extraction oflarge quantities of data. In an effort to alleviatethis bottleneck within high-throughputglycomic projects, the NIBRT team havedeveloped a web-based tool that interfaceswith the Waters chromatography softwarepackage to improve and automate the exportof data to various file formats for subsequentanalysis. The modular architecture of the toolalso facilitates the manipulation of data fromother data management systems.

The NIBRT team are now working to integrateGlycoExtractor with the EUROCarbDBframework to provide a comprehensive high-throughput HPLC data analysis platform forthe storage and annotation of experimentaldata. The integration of next generationbioinformatic tools will further thedevelopment of unified approaches forhandling large scale glycomics data initiativeswith applications in biomarker discovery

This research was partially supported by

EUROCarbDB, a research infrastructure designstudy funded by the EU 6th FrameworkProgramme. Prospective users can access theGlycoExtractor tool onhttp://glycobase.nibrt.ie:8080/DemoGlycoExtractor/mainPage.ReferenceGlycoExtractor: A web-based interface for highthroughput processing of HPLC-Glycan dataNatalia V. Artemenko, Matthew P. Campbell, and PaulineM. Rudd Journal of Proteome Research, 2010, 9 (4), pp2037–2041

NIBRT researchers Dr Matthew Campbell and Dr NataliaArtemenko who developed GlycoExtractor

Zebrafish model gives insights into diabetic blindness

New research led by Conway Fellow DrBreandán Kennedy indicates that treatmentof diabetic blindness should look atprotecting the neurons responsible for colourvision in the eye and not just targeting theblood vessels as is currently the practice.

Nearly 2.5 million people worldwide are blinddue to diabetic retinopathy. This secondarycomplication of diabetes activates the growthof new leaky blood vessels in the eye and isresponsible for the death of photoreceptors,the neurons that send visual messages to ourbrain.

Until now, it was unclear if the changes tovessels and neurons occurred independently ofone other and which type of retinal neuron is

most likely to die as a result of the raisedglucose levels seen in diabetes.

Dr Kennedy and his team found that new bloodvessels and the neuronal cell death in diabeticretinopathy can arise independently of eachother. In addition, they identified that conephotoreceptor neurons, those involved incolour vision and used in daylight, are mostaffected by the high glucose levels.

The research team made their observationsusing a novel zebrafish model of diabetes,which resembles the early stages of diabeticretinopathy in humans. It is an excitingdevelopment for the group who now hope tofurther extend their research and establish amodel of late stage diabetic disease.

Commenting on the research, Dr Kennedysaid, “By establishing a robust model for earlyand late stage diabetic retinopathy, we wouldhope to better understand the progression ofthe disease and pave the way for identifyingnew drug targets for its successful treatment”.

The research was funded through ScienceFoundation Ireland and the Health ResearchBoard.

Reference:

Predominant cone photoreceptor dysfunction in ahyperglycaemic model of non-proliferative diabeticretinopathy. Yolanda Alvarez, Jenneth Chen, AlisonReynolds, Nore Waghorne, John J. O’Connor, BreandanKennedy. Disease Models & Mechanisms (2010)

May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3

Reference Collins L et al. Probing charge screening dynamics and electrochemical processes at the solid–liquid interface with electrochemical force microscopy. Nature Communications| 5:3871| DOI:10.1038/ ncomms4871.

In seasonally calving herds, the aim is to achieve conception by 75 to 85 days, depending on breed, following parturition so that calving-to-calving intervals are maintained at 365 days.

Reference Cleary JA, Doherty W, Evans P, Malthouse JP. Hemiacetal stabilization in a chymotrypsin inhibitor complex and the reactivity of the hydroxyl group of the catalytic serine residue of chymotrypsin. Biochim Biophys Acta. 2014 Jun;1844(6):1119-27. doi: 10.1016/j.bbapap.2014.03.008. Epub 2014 Mar 21.

M. A. Crowe, M. G. Diskin and E. J. Williams. Parturition to resumption of ovarian cyclicity: comparative aspects of beef and dairy cows. Animal (2014) Mar 28: 1 -14

Field testing eCDSS (electronic clinical descion support system) for connectivity in rural northern Malawi (l-r) Dr Chris Watson (UCD) and Dr John O’Donoghue (Imperial College London) as part of Managing Type 2 Diabetes in Malawi, Africa (MTIMA) project.

Dr Lorna Lopez (Cagney group) partners with her neuron teddy to give “Clues to understanding your brain” as part of Soapbox Science Dublin 2014

Aine Lawlor launches ICORG’s first awareness campaign for International Clinical Trials Day with her assistants in the Institute.

Irish biopharmaceutical developmentcompany, Sigmoid Pharma recently scoopedthe overall Innovation of the Year award atthe inaugural Irish Times All-IslandInnovation Awards. The life-science SME,founded by UCD pharmacology graduate, DrIvan Coulter, has actively collaborated withConway Fellow, Professor Cormac Taylorsince being granted a Science FoundationIreland industry research partnership awardin 2004.

The Irish Times award recognises the stellarinnovative performance of Sigmoid Pharma intheir application of research and development.The company has developed two new drugtechnologies, LEDDS™ and SmPill™, which notonly enhance the solubility and permeability ofthe drug but can deliver it to targeted locationsin the gastrointestinal tract, including thecolon.

The Sigmoid Pharma-Taylor collaboration isfacilitating the development of a newtherapeutic approach for the treatment ofinflammatory bowel disease (IBD) by bringingtogether the research methodology of theTaylor group with the proprietaryliquid/emulsion drug delivery system,LEDDS®, developed by Sigmoid Pharma.

Commenting on the award, Professor Taylorsaid, “We are delighted for Dr Coulter and histeam and indeed it reflects well on ourpartnership. A key driver of successfulscientific research in 2010 is meaningfulinteraction of academia with industry that

results in both academic outputs and theapplication of research toward clinical productdevelopment with indigenous companies.”

Commenting on the Taylor collaboration, DrCoulter said, “The collaboration with the Taylorlaboratory clearly demonstrates the potentialthat can be realised through focusedapplication of basic research. The developmentof a smart economy will depend on like-mindedcollaborative partners identifying opportunitiesand realising basic and applied researchsynergies. This collaboration, initiated througha SFI research supplement, highlights thepotential that innovative indigenous companiesworking with academia can realise.”

Taylor’s collaboration with Sigmoid Pharma hascertainly been successful by these metrics withthree co-authored publications to date in two ofthe highest ranking scientific journals in thefield, Gastroenterology and Proceeding of theNational Academy of Sciences, as well as thegeneration of proprietary innovative productsand the creation of high-skilled jobs.

More than 15,000 people in Ireland andmillions of people worldwide are living with thesymptoms IBD today. Current therapeuticoptions for this chronic debilitating disease arevery limited with surgery often being the onlyviable option. The Sigmoid product, currentlyin a phase II clinical study, uniquely enablesoral delivery of a powerful drug withoutcausing systemic side-effects.

Under normal conditions, the gastrointestinal

tract is lined with cells that block the contentsof the gut from leaking into the intestine. In anIBD patient, this barrier is broken and thecontents of the gut leak out into surroundingareas. The research team in UCD Conway useda model of IBD and, by applying a new class ofdrugs known as hydroxylase inhibitors, wereable to almost completely reverse thesymptoms of the disease.

“When we applied these new drugs to our IBDmodel, the gut was tricked into thinking that itwas being deprived of oxygen. This activatedprotective pathways, which in turn preventedthe death of the cells that line thegastrointestinal tract,” explained ProfessorTaylor. “Our pre-clinical trial data can nowinform the next phase Sigmoid Pharma productdevelopment pipeline”.

In addition to the product that is currently inphase II clinical studies, Sigmoid Pharma isdeveloping a LEDDS™-enabled formulation ofthe hydroxylase inhibitordimethyloxaloylglycine (DMOG) to bring abouteffective, safe and targeted delivery of thispotential therapeutic agent.

Conway collaborator scoops Irish Times Innovation Award

Conway researchers led by Dr. TaraMcMorrow and Professor Michael Ryan havesuccessfully secured €485,500 in funding aspart of an overall award to the SystemsBiology towards Novel Chronic KidneyDisease Diagnosis and Treatment (SysKid)consortium under the European Union FP7programme.

Syskid (www.SysKid.eu) was established tofurther our understanding of chronic kidney

disease (CKD) and improve patient treatment,with particular focus on CKD arising fromdiabetes and hypertension. The multi-disciplinary research consortium has 25partners (16 universities, 9 industry partners)from 15 countries and the project is due to runfor five years.

The UCD Conway team, including postdoctoralresearchers Dr. Craig Slattery and Dr. NataliaMartin, will utilise cell culture and animal

models to identify processes involved in earlyCKD progression and investigate novelstrategies for preventing and slowing theprogression of the disease. These studies willbe integrated with clinical and epidemiologicalstudies across the consortium using systemsbiology methodologies in order to develop newdiagnostic strategies and treatment options toprevent CKD development. [email protected] for details of a PhDposition currently available.

Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Meta-analysis by UCD researchers led byConway Fellow, Professor Denis Shields hasdetermined that there is no clear evidencethat particular defective viral sequences inthe HIV-1 nef gene or certain regions of theprotein play a significant role in diseaseprogression.

HIV-infected patients can be categorised onthe basis of the number of years it takes forthem to progress to AIDS. Some patientsmaintain stable CD4 lymphocyte counts anddo not go on to develop AIDS even after morethan 10 years of infection.

Scientists are curious as to why these long-term, non- progressor (LTNP) patients do notdevelop AIDS. This may reflect differences inthe host, viral genetics or environmentalfactors that could potentially be exploited forthe treatment of the disease.

Studies in model organisms have shown thatinfection with nef-deficient virus shows anattenuated course of infection and some

studies in humans have shown that nonprogression was associated with grossdeletions in the nef gene.

However, much of the research in the area todate has been based on observational or casestudies rather than rigorous, systematicscientific evaluation. This work by doctoralcandidate Ravindra Pushker set out todetermine in a substantially larger sample setif any association exists between diseaseprogression and particular amino aciddifferences or deletions within the nef gene.

On a per patient basis, there was no excess ofLTNP patients with one or more defective nefsequences when compared to progressors.While the high frequency of amino acidreplacement at particular residues is indicativeof rapid evolvement, permutation testingshowed that residues with more replacementsthan expected were not statistically significant.

The researchers conclude that current dataprovides no evidence that individual residues

of HIV nef are critical in determining the rateof disease progression. Professor DenisShields believes that searches for modifiers ofprogression rates should now focus on otherhost and viral factors. “Systematic evaluationof large quantities of data by bioinformaticscan be just as important in refutinghypotheses that are current in the literature, asit is in discovering unknown patterns”, he said.

This research was funded through ScienceFoundation Ireland and University CollegeDublin.

Reference:Meta-analysis to test the association of HIV-1 nef aminoacid differences and deletions with disease progression.Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields.Journal of Virology, Apr 2010 p3644-3653

GlycoExtractor advances glycan data manipulation

Glycomics needs the supporting frameworkof extensive, well-curated databases andflexible analytical tools. Currently, this fieldof study lacks the established,comprehensive and centralised datacollections, standards and informationreporting protocols that exist withingenomics and proteomics.

Researchers, Dr Natalia Artemenko and DrMatthew Campbell from the National Instituteof Bioprocessing Research & Training (NIBRT)led by Conway Fellow, Professor Pauline Ruddhave developed an open access, web-basedinterface that facilitates extraction, queryingand sharing of HPLC-glycan data generated inhigh throughput processes.

Glycosylation is the most common andstructurally diverse post-translationalmodification of proteins. More than half of allgene products have been shown to beglycosylated. With many specific glycans orglycoforms showing potential as cancerbiomarkers, there is an increasing need todevelop high throughput, highly sensitive androbust strategies that detail the glycome of

cells, tissues and fluids.

Commercial packages that support HPLCinstruments cannot facilitate the extraction oflarge quantities of data. In an effort to alleviatethis bottleneck within high-throughputglycomic projects, the NIBRT team havedeveloped a web-based tool that interfaceswith the Waters chromatography softwarepackage to improve and automate the exportof data to various file formats for subsequentanalysis. The modular architecture of the toolalso facilitates the manipulation of data fromother data management systems.

The NIBRT team are now working to integrateGlycoExtractor with the EUROCarbDBframework to provide a comprehensive high-throughput HPLC data analysis platform forthe storage and annotation of experimentaldata. The integration of next generationbioinformatic tools will further thedevelopment of unified approaches forhandling large scale glycomics data initiativeswith applications in biomarker discovery

This research was partially supported by

EUROCarbDB, a research infrastructure designstudy funded by the EU 6th FrameworkProgramme. Prospective users can access theGlycoExtractor tool onhttp://glycobase.nibrt.ie:8080/DemoGlycoExtractor/mainPage.ReferenceGlycoExtractor: A web-based interface for highthroughput processing of HPLC-Glycan dataNatalia V. Artemenko, Matthew P. Campbell, and PaulineM. Rudd Journal of Proteome Research, 2010, 9 (4), pp2037–2041

NIBRT researchers Dr Matthew Campbell and Dr NataliaArtemenko who developed GlycoExtractor

Zebrafish model gives insights into diabetic blindness

New research led by Conway Fellow DrBreandán Kennedy indicates that treatmentof diabetic blindness should look atprotecting the neurons responsible for colourvision in the eye and not just targeting theblood vessels as is currently the practice.

Nearly 2.5 million people worldwide are blinddue to diabetic retinopathy. This secondarycomplication of diabetes activates the growthof new leaky blood vessels in the eye and isresponsible for the death of photoreceptors,the neurons that send visual messages to ourbrain.

Until now, it was unclear if the changes tovessels and neurons occurred independently ofone other and which type of retinal neuron is

most likely to die as a result of the raisedglucose levels seen in diabetes.

Dr Kennedy and his team found that new bloodvessels and the neuronal cell death in diabeticretinopathy can arise independently of eachother. In addition, they identified that conephotoreceptor neurons, those involved incolour vision and used in daylight, are mostaffected by the high glucose levels.

The research team made their observationsusing a novel zebrafish model of diabetes,which resembles the early stages of diabeticretinopathy in humans. It is an excitingdevelopment for the group who now hope tofurther extend their research and establish amodel of late stage diabetic disease.

Commenting on the research, Dr Kennedysaid, “By establishing a robust model for earlyand late stage diabetic retinopathy, we wouldhope to better understand the progression ofthe disease and pave the way for identifyingnew drug targets for its successful treatment”.

The research was funded through ScienceFoundation Ireland and the Health ResearchBoard.

Reference:

Predominant cone photoreceptor dysfunction in ahyperglycaemic model of non-proliferative diabeticretinopathy. Yolanda Alvarez, Jenneth Chen, AlisonReynolds, Nore Waghorne, John J. O’Connor, BreandanKennedy. Disease Models & Mechanisms (2010)

May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3

Irish biopharmaceutical developmentcompany, Sigmoid Pharma recently scoopedthe overall Innovation of the Year award atthe inaugural Irish Times All-IslandInnovation Awards. The life-science SME,founded by UCD pharmacology graduate, DrIvan Coulter, has actively collaborated withConway Fellow, Professor Cormac Taylorsince being granted a Science FoundationIreland industry research partnership awardin 2004.

The Irish Times award recognises the stellarinnovative performance of Sigmoid Pharma intheir application of research and development.The company has developed two new drugtechnologies, LEDDS™ and SmPill™, which notonly enhance the solubility and permeability ofthe drug but can deliver it to targeted locationsin the gastrointestinal tract, including thecolon.

The Sigmoid Pharma-Taylor collaboration isfacilitating the development of a newtherapeutic approach for the treatment ofinflammatory bowel disease (IBD) by bringingtogether the research methodology of theTaylor group with the proprietaryliquid/emulsion drug delivery system,LEDDS®, developed by Sigmoid Pharma.

Commenting on the award, Professor Taylorsaid, “We are delighted for Dr Coulter and histeam and indeed it reflects well on ourpartnership. A key driver of successfulscientific research in 2010 is meaningfulinteraction of academia with industry that

results in both academic outputs and theapplication of research toward clinical productdevelopment with indigenous companies.”

Commenting on the Taylor collaboration, DrCoulter said, “The collaboration with the Taylorlaboratory clearly demonstrates the potentialthat can be realised through focusedapplication of basic research. The developmentof a smart economy will depend on like-mindedcollaborative partners identifying opportunitiesand realising basic and applied researchsynergies. This collaboration, initiated througha SFI research supplement, highlights thepotential that innovative indigenous companiesworking with academia can realise.”

Taylor’s collaboration with Sigmoid Pharma hascertainly been successful by these metrics withthree co-authored publications to date in two ofthe highest ranking scientific journals in thefield, Gastroenterology and Proceeding of theNational Academy of Sciences, as well as thegeneration of proprietary innovative productsand the creation of high-skilled jobs.

More than 15,000 people in Ireland andmillions of people worldwide are living with thesymptoms IBD today. Current therapeuticoptions for this chronic debilitating disease arevery limited with surgery often being the onlyviable option. The Sigmoid product, currentlyin a phase II clinical study, uniquely enablesoral delivery of a powerful drug withoutcausing systemic side-effects.

Under normal conditions, the gastrointestinal

tract is lined with cells that block the contentsof the gut from leaking into the intestine. In anIBD patient, this barrier is broken and thecontents of the gut leak out into surroundingareas. The research team in UCD Conway useda model of IBD and, by applying a new class ofdrugs known as hydroxylase inhibitors, wereable to almost completely reverse thesymptoms of the disease.

“When we applied these new drugs to our IBDmodel, the gut was tricked into thinking that itwas being deprived of oxygen. This activatedprotective pathways, which in turn preventedthe death of the cells that line thegastrointestinal tract,” explained ProfessorTaylor. “Our pre-clinical trial data can nowinform the next phase Sigmoid Pharma productdevelopment pipeline”.

In addition to the product that is currently inphase II clinical studies, Sigmoid Pharma isdeveloping a LEDDS™-enabled formulation ofthe hydroxylase inhibitordimethyloxaloylglycine (DMOG) to bring abouteffective, safe and targeted delivery of thispotential therapeutic agent.

Conway collaborator scoops Irish Times Innovation Award

Conway researchers led by Dr. TaraMcMorrow and Professor Michael Ryan havesuccessfully secured €485,500 in funding aspart of an overall award to the SystemsBiology towards Novel Chronic KidneyDisease Diagnosis and Treatment (SysKid)consortium under the European Union FP7programme.

Syskid (www.SysKid.eu) was established tofurther our understanding of chronic kidney

disease (CKD) and improve patient treatment,with particular focus on CKD arising fromdiabetes and hypertension. The multi-disciplinary research consortium has 25partners (16 universities, 9 industry partners)from 15 countries and the project is due to runfor five years.

The UCD Conway team, including postdoctoralresearchers Dr. Craig Slattery and Dr. NataliaMartin, will utilise cell culture and animal

models to identify processes involved in earlyCKD progression and investigate novelstrategies for preventing and slowing theprogression of the disease. These studies willbe integrated with clinical and epidemiologicalstudies across the consortium using systemsbiology methodologies in order to develop newdiagnostic strategies and treatment options toprevent CKD development. [email protected] for details of a PhDposition currently available.

Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Meta-analysis by UCD researchers led byConway Fellow, Professor Denis Shields hasdetermined that there is no clear evidencethat particular defective viral sequences inthe HIV-1 nef gene or certain regions of theprotein play a significant role in diseaseprogression.

HIV-infected patients can be categorised onthe basis of the number of years it takes forthem to progress to AIDS. Some patientsmaintain stable CD4 lymphocyte counts anddo not go on to develop AIDS even after morethan 10 years of infection.

Scientists are curious as to why these long-term, non- progressor (LTNP) patients do notdevelop AIDS. This may reflect differences inthe host, viral genetics or environmentalfactors that could potentially be exploited forthe treatment of the disease.

Studies in model organisms have shown thatinfection with nef-deficient virus shows anattenuated course of infection and some

studies in humans have shown that nonprogression was associated with grossdeletions in the nef gene.

However, much of the research in the area todate has been based on observational or casestudies rather than rigorous, systematicscientific evaluation. This work by doctoralcandidate Ravindra Pushker set out todetermine in a substantially larger sample setif any association exists between diseaseprogression and particular amino aciddifferences or deletions within the nef gene.

On a per patient basis, there was no excess ofLTNP patients with one or more defective nefsequences when compared to progressors.While the high frequency of amino acidreplacement at particular residues is indicativeof rapid evolvement, permutation testingshowed that residues with more replacementsthan expected were not statistically significant.

The researchers conclude that current dataprovides no evidence that individual residues

of HIV nef are critical in determining the rateof disease progression. Professor DenisShields believes that searches for modifiers ofprogression rates should now focus on otherhost and viral factors. “Systematic evaluationof large quantities of data by bioinformaticscan be just as important in refutinghypotheses that are current in the literature, asit is in discovering unknown patterns”, he said.

This research was funded through ScienceFoundation Ireland and University CollegeDublin.

Reference:Meta-analysis to test the association of HIV-1 nef aminoacid differences and deletions with disease progression.Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields.Journal of Virology, Apr 2010 p3644-3653

GlycoExtractor advances glycan data manipulation

Glycomics needs the supporting frameworkof extensive, well-curated databases andflexible analytical tools. Currently, this fieldof study lacks the established,comprehensive and centralised datacollections, standards and informationreporting protocols that exist withingenomics and proteomics.

Researchers, Dr Natalia Artemenko and DrMatthew Campbell from the National Instituteof Bioprocessing Research & Training (NIBRT)led by Conway Fellow, Professor Pauline Ruddhave developed an open access, web-basedinterface that facilitates extraction, queryingand sharing of HPLC-glycan data generated inhigh throughput processes.

Glycosylation is the most common andstructurally diverse post-translationalmodification of proteins. More than half of allgene products have been shown to beglycosylated. With many specific glycans orglycoforms showing potential as cancerbiomarkers, there is an increasing need todevelop high throughput, highly sensitive androbust strategies that detail the glycome of

cells, tissues and fluids.

Commercial packages that support HPLCinstruments cannot facilitate the extraction oflarge quantities of data. In an effort to alleviatethis bottleneck within high-throughputglycomic projects, the NIBRT team havedeveloped a web-based tool that interfaceswith the Waters chromatography softwarepackage to improve and automate the exportof data to various file formats for subsequentanalysis. The modular architecture of the toolalso facilitates the manipulation of data fromother data management systems.

The NIBRT team are now working to integrateGlycoExtractor with the EUROCarbDBframework to provide a comprehensive high-throughput HPLC data analysis platform forthe storage and annotation of experimentaldata. The integration of next generationbioinformatic tools will further thedevelopment of unified approaches forhandling large scale glycomics data initiativeswith applications in biomarker discovery

This research was partially supported by

EUROCarbDB, a research infrastructure designstudy funded by the EU 6th FrameworkProgramme. Prospective users can access theGlycoExtractor tool onhttp://glycobase.nibrt.ie:8080/DemoGlycoExtractor/mainPage.ReferenceGlycoExtractor: A web-based interface for highthroughput processing of HPLC-Glycan dataNatalia V. Artemenko, Matthew P. Campbell, and PaulineM. Rudd Journal of Proteome Research, 2010, 9 (4), pp2037–2041

NIBRT researchers Dr Matthew Campbell and Dr NataliaArtemenko who developed GlycoExtractor

Zebrafish model gives insights into diabetic blindness

New research led by Conway Fellow DrBreandán Kennedy indicates that treatmentof diabetic blindness should look atprotecting the neurons responsible for colourvision in the eye and not just targeting theblood vessels as is currently the practice.

Nearly 2.5 million people worldwide are blinddue to diabetic retinopathy. This secondarycomplication of diabetes activates the growthof new leaky blood vessels in the eye and isresponsible for the death of photoreceptors,the neurons that send visual messages to ourbrain.

Until now, it was unclear if the changes tovessels and neurons occurred independently ofone other and which type of retinal neuron is

most likely to die as a result of the raisedglucose levels seen in diabetes.

Dr Kennedy and his team found that new bloodvessels and the neuronal cell death in diabeticretinopathy can arise independently of eachother. In addition, they identified that conephotoreceptor neurons, those involved incolour vision and used in daylight, are mostaffected by the high glucose levels.

The research team made their observationsusing a novel zebrafish model of diabetes,which resembles the early stages of diabeticretinopathy in humans. It is an excitingdevelopment for the group who now hope tofurther extend their research and establish amodel of late stage diabetic disease.

Commenting on the research, Dr Kennedysaid, “By establishing a robust model for earlyand late stage diabetic retinopathy, we wouldhope to better understand the progression ofthe disease and pave the way for identifyingnew drug targets for its successful treatment”.

The research was funded through ScienceFoundation Ireland and the Health ResearchBoard.

Reference:

Predominant cone photoreceptor dysfunction in ahyperglycaemic model of non-proliferative diabeticretinopathy. Yolanda Alvarez, Jenneth Chen, AlisonReynolds, Nore Waghorne, John J. O’Connor, BreandanKennedy. Disease Models & Mechanisms (2010)

May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3

Tailoring treatment in ovarian cancerThe prognosis for ovarian cancer patients is poor with only 3 out of 10 women living at least 5 years after diagnosis. Clinicians urgently need the tools to provide a more accurate prognosis for patients in terms of whether particular chemotherapeutic agents will be of benefit in their treatment.

UCD researchers led by Conway Fellow, Dr Amanda McCann have now identified the protein MAD2 as a potential prognostic marker in a number of histological subtypes of ovarian cancer. This may help provide more tailored approaches to the treatment of ovarian cancer patients.

MAD2 is one of the protein components of the spindle assembly checkpoint (SAC) present in all eukaryotes that prevents chromosomes from segregating incorrectly during cell division. Paclitaxel (Taxol) is the first-line chemotherapeutic

agent used to treat ovarian cancer in combination with platinum agents. It works by interfering with the spindle microtubule dynamics to cause cell cycle arrest and cell death (apoptosis), a function mediated by MAD2.

“In this study, we were able to show that low MAD2 nuclear expression associates with a poorer response to chemotherapy and this was exemplified by a shorter time to recurrence of the disease in the patient cohort whose cancer subtype included serous, endometrioid and mixed histologies”, explained Barbara McGrogan, the lead author and doctoral candidate in the McCann group.

Serous and endometrioid tumours are biologically different, however, in clinical practice they are still treated similarly.

Dr McCann said, “The fact that decreased MAD2 nuclear expression identifies those women with a shorter recurrence

Irish biopharmaceutical developmentcompany, Sigmoid Pharma recently scoopedthe overall Innovation of the Year award atthe inaugural Irish Times All-IslandInnovation Awards. The life-science SME,founded by UCD pharmacology graduate, DrIvan Coulter, has actively collaborated withConway Fellow, Professor Cormac Taylorsince being granted a Science FoundationIreland industry research partnership awardin 2004.

The Irish Times award recognises the stellarinnovative performance of Sigmoid Pharma intheir application of research and development.The company has developed two new drugtechnologies, LEDDS™ and SmPill™, which notonly enhance the solubility and permeability ofthe drug but can deliver it to targeted locationsin the gastrointestinal tract, including thecolon.

The Sigmoid Pharma-Taylor collaboration isfacilitating the development of a newtherapeutic approach for the treatment ofinflammatory bowel disease (IBD) by bringingtogether the research methodology of theTaylor group with the proprietaryliquid/emulsion drug delivery system,LEDDS®, developed by Sigmoid Pharma.

Commenting on the award, Professor Taylorsaid, “We are delighted for Dr Coulter and histeam and indeed it reflects well on ourpartnership. A key driver of successfulscientific research in 2010 is meaningfulinteraction of academia with industry that

results in both academic outputs and theapplication of research toward clinical productdevelopment with indigenous companies.”

Commenting on the Taylor collaboration, DrCoulter said, “The collaboration with the Taylorlaboratory clearly demonstrates the potentialthat can be realised through focusedapplication of basic research. The developmentof a smart economy will depend on like-mindedcollaborative partners identifying opportunitiesand realising basic and applied researchsynergies. This collaboration, initiated througha SFI research supplement, highlights thepotential that innovative indigenous companiesworking with academia can realise.”

Taylor’s collaboration with Sigmoid Pharma hascertainly been successful by these metrics withthree co-authored publications to date in two ofthe highest ranking scientific journals in thefield, Gastroenterology and Proceeding of theNational Academy of Sciences, as well as thegeneration of proprietary innovative productsand the creation of high-skilled jobs.

More than 15,000 people in Ireland andmillions of people worldwide are living with thesymptoms IBD today. Current therapeuticoptions for this chronic debilitating disease arevery limited with surgery often being the onlyviable option. The Sigmoid product, currentlyin a phase II clinical study, uniquely enablesoral delivery of a powerful drug withoutcausing systemic side-effects.

Under normal conditions, the gastrointestinal

tract is lined with cells that block the contentsof the gut from leaking into the intestine. In anIBD patient, this barrier is broken and thecontents of the gut leak out into surroundingareas. The research team in UCD Conway useda model of IBD and, by applying a new class ofdrugs known as hydroxylase inhibitors, wereable to almost completely reverse thesymptoms of the disease.

“When we applied these new drugs to our IBDmodel, the gut was tricked into thinking that itwas being deprived of oxygen. This activatedprotective pathways, which in turn preventedthe death of the cells that line thegastrointestinal tract,” explained ProfessorTaylor. “Our pre-clinical trial data can nowinform the next phase Sigmoid Pharma productdevelopment pipeline”.

In addition to the product that is currently inphase II clinical studies, Sigmoid Pharma isdeveloping a LEDDS™-enabled formulation ofthe hydroxylase inhibitordimethyloxaloylglycine (DMOG) to bring abouteffective, safe and targeted delivery of thispotential therapeutic agent.

Conway collaborator scoops Irish Times Innovation Award

Conway researchers led by Dr. TaraMcMorrow and Professor Michael Ryan havesuccessfully secured €485,500 in funding aspart of an overall award to the SystemsBiology towards Novel Chronic KidneyDisease Diagnosis and Treatment (SysKid)consortium under the European Union FP7programme.

Syskid (www.SysKid.eu) was established tofurther our understanding of chronic kidney

disease (CKD) and improve patient treatment,with particular focus on CKD arising fromdiabetes and hypertension. The multi-disciplinary research consortium has 25partners (16 universities, 9 industry partners)from 15 countries and the project is due to runfor five years.

The UCD Conway team, including postdoctoralresearchers Dr. Craig Slattery and Dr. NataliaMartin, will utilise cell culture and animal

models to identify processes involved in earlyCKD progression and investigate novelstrategies for preventing and slowing theprogression of the disease. These studies willbe integrated with clinical and epidemiologicalstudies across the consortium using systemsbiology methodologies in order to develop newdiagnostic strategies and treatment options toprevent CKD development. [email protected] for details of a PhDposition currently available.

Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Meta-analysis by UCD researchers led byConway Fellow, Professor Denis Shields hasdetermined that there is no clear evidencethat particular defective viral sequences inthe HIV-1 nef gene or certain regions of theprotein play a significant role in diseaseprogression.

HIV-infected patients can be categorised onthe basis of the number of years it takes forthem to progress to AIDS. Some patientsmaintain stable CD4 lymphocyte counts anddo not go on to develop AIDS even after morethan 10 years of infection.

Scientists are curious as to why these long-term, non- progressor (LTNP) patients do notdevelop AIDS. This may reflect differences inthe host, viral genetics or environmentalfactors that could potentially be exploited forthe treatment of the disease.

Studies in model organisms have shown thatinfection with nef-deficient virus shows anattenuated course of infection and some

studies in humans have shown that nonprogression was associated with grossdeletions in the nef gene.

However, much of the research in the area todate has been based on observational or casestudies rather than rigorous, systematicscientific evaluation. This work by doctoralcandidate Ravindra Pushker set out todetermine in a substantially larger sample setif any association exists between diseaseprogression and particular amino aciddifferences or deletions within the nef gene.

On a per patient basis, there was no excess ofLTNP patients with one or more defective nefsequences when compared to progressors.While the high frequency of amino acidreplacement at particular residues is indicativeof rapid evolvement, permutation testingshowed that residues with more replacementsthan expected were not statistically significant.

The researchers conclude that current dataprovides no evidence that individual residues

of HIV nef are critical in determining the rateof disease progression. Professor DenisShields believes that searches for modifiers ofprogression rates should now focus on otherhost and viral factors. “Systematic evaluationof large quantities of data by bioinformaticscan be just as important in refutinghypotheses that are current in the literature, asit is in discovering unknown patterns”, he said.

This research was funded through ScienceFoundation Ireland and University CollegeDublin.

Reference:Meta-analysis to test the association of HIV-1 nef aminoacid differences and deletions with disease progression.Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields.Journal of Virology, Apr 2010 p3644-3653

GlycoExtractor advances glycan data manipulation

Glycomics needs the supporting frameworkof extensive, well-curated databases andflexible analytical tools. Currently, this fieldof study lacks the established,comprehensive and centralised datacollections, standards and informationreporting protocols that exist withingenomics and proteomics.

Researchers, Dr Natalia Artemenko and DrMatthew Campbell from the National Instituteof Bioprocessing Research & Training (NIBRT)led by Conway Fellow, Professor Pauline Ruddhave developed an open access, web-basedinterface that facilitates extraction, queryingand sharing of HPLC-glycan data generated inhigh throughput processes.

Glycosylation is the most common andstructurally diverse post-translationalmodification of proteins. More than half of allgene products have been shown to beglycosylated. With many specific glycans orglycoforms showing potential as cancerbiomarkers, there is an increasing need todevelop high throughput, highly sensitive androbust strategies that detail the glycome of

cells, tissues and fluids.

Commercial packages that support HPLCinstruments cannot facilitate the extraction oflarge quantities of data. In an effort to alleviatethis bottleneck within high-throughputglycomic projects, the NIBRT team havedeveloped a web-based tool that interfaceswith the Waters chromatography softwarepackage to improve and automate the exportof data to various file formats for subsequentanalysis. The modular architecture of the toolalso facilitates the manipulation of data fromother data management systems.

The NIBRT team are now working to integrateGlycoExtractor with the EUROCarbDBframework to provide a comprehensive high-throughput HPLC data analysis platform forthe storage and annotation of experimentaldata. The integration of next generationbioinformatic tools will further thedevelopment of unified approaches forhandling large scale glycomics data initiativeswith applications in biomarker discovery

This research was partially supported by

EUROCarbDB, a research infrastructure designstudy funded by the EU 6th FrameworkProgramme. Prospective users can access theGlycoExtractor tool onhttp://glycobase.nibrt.ie:8080/DemoGlycoExtractor/mainPage.ReferenceGlycoExtractor: A web-based interface for highthroughput processing of HPLC-Glycan dataNatalia V. Artemenko, Matthew P. Campbell, and PaulineM. Rudd Journal of Proteome Research, 2010, 9 (4), pp2037–2041

NIBRT researchers Dr Matthew Campbell and Dr NataliaArtemenko who developed GlycoExtractor

Zebrafish model gives insights into diabetic blindness

New research led by Conway Fellow DrBreandán Kennedy indicates that treatmentof diabetic blindness should look atprotecting the neurons responsible for colourvision in the eye and not just targeting theblood vessels as is currently the practice.

Nearly 2.5 million people worldwide are blinddue to diabetic retinopathy. This secondarycomplication of diabetes activates the growthof new leaky blood vessels in the eye and isresponsible for the death of photoreceptors,the neurons that send visual messages to ourbrain.

Until now, it was unclear if the changes tovessels and neurons occurred independently ofone other and which type of retinal neuron is

most likely to die as a result of the raisedglucose levels seen in diabetes.

Dr Kennedy and his team found that new bloodvessels and the neuronal cell death in diabeticretinopathy can arise independently of eachother. In addition, they identified that conephotoreceptor neurons, those involved incolour vision and used in daylight, are mostaffected by the high glucose levels.

The research team made their observationsusing a novel zebrafish model of diabetes,which resembles the early stages of diabeticretinopathy in humans. It is an excitingdevelopment for the group who now hope tofurther extend their research and establish amodel of late stage diabetic disease.

Commenting on the research, Dr Kennedysaid, “By establishing a robust model for earlyand late stage diabetic retinopathy, we wouldhope to better understand the progression ofthe disease and pave the way for identifyingnew drug targets for its successful treatment”.

The research was funded through ScienceFoundation Ireland and the Health ResearchBoard.

Reference:

Predominant cone photoreceptor dysfunction in ahyperglycaemic model of non-proliferative diabeticretinopathy. Yolanda Alvarez, Jenneth Chen, AlisonReynolds, Nore Waghorne, John J. O’Connor, BreandanKennedy. Disease Models & Mechanisms (2010)

May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3

Predicting response to endocrine therapies The majority of women diagnosed with breast cancer have estrogen receptor (ER)-positive tumours, and are treated with tamoxifen. While this drug has revolutionised how we treat breast cancer, resistance is a common problem.

New research led by Conway Fellow, Prof William Gallagher in the Irish Cancer Society Collaborative Cancer Research

Centre BREAST-PREDICT found that ER-positive breast tumours with high levels of a protein called PRDX1 had a better outcome than those with low PRDX1 levels.

This study identified a unique role for PRDX1 in protecting the estrogen receptor from oxidative stress and so maintaining levels of this protein in the tumour cells. As tamoxifen targets the

Irish biopharmaceutical developmentcompany, Sigmoid Pharma recently scoopedthe overall Innovation of the Year award atthe inaugural Irish Times All-IslandInnovation Awards. The life-science SME,founded by UCD pharmacology graduate, DrIvan Coulter, has actively collaborated withConway Fellow, Professor Cormac Taylorsince being granted a Science FoundationIreland industry research partnership awardin 2004.

The Irish Times award recognises the stellarinnovative performance of Sigmoid Pharma intheir application of research and development.The company has developed two new drugtechnologies, LEDDS™ and SmPill™, which notonly enhance the solubility and permeability ofthe drug but can deliver it to targeted locationsin the gastrointestinal tract, including thecolon.

The Sigmoid Pharma-Taylor collaboration isfacilitating the development of a newtherapeutic approach for the treatment ofinflammatory bowel disease (IBD) by bringingtogether the research methodology of theTaylor group with the proprietaryliquid/emulsion drug delivery system,LEDDS®, developed by Sigmoid Pharma.

Commenting on the award, Professor Taylorsaid, “We are delighted for Dr Coulter and histeam and indeed it reflects well on ourpartnership. A key driver of successfulscientific research in 2010 is meaningfulinteraction of academia with industry that

results in both academic outputs and theapplication of research toward clinical productdevelopment with indigenous companies.”

Commenting on the Taylor collaboration, DrCoulter said, “The collaboration with the Taylorlaboratory clearly demonstrates the potentialthat can be realised through focusedapplication of basic research. The developmentof a smart economy will depend on like-mindedcollaborative partners identifying opportunitiesand realising basic and applied researchsynergies. This collaboration, initiated througha SFI research supplement, highlights thepotential that innovative indigenous companiesworking with academia can realise.”

Taylor’s collaboration with Sigmoid Pharma hascertainly been successful by these metrics withthree co-authored publications to date in two ofthe highest ranking scientific journals in thefield, Gastroenterology and Proceeding of theNational Academy of Sciences, as well as thegeneration of proprietary innovative productsand the creation of high-skilled jobs.

More than 15,000 people in Ireland andmillions of people worldwide are living with thesymptoms IBD today. Current therapeuticoptions for this chronic debilitating disease arevery limited with surgery often being the onlyviable option. The Sigmoid product, currentlyin a phase II clinical study, uniquely enablesoral delivery of a powerful drug withoutcausing systemic side-effects.

Under normal conditions, the gastrointestinal

tract is lined with cells that block the contentsof the gut from leaking into the intestine. In anIBD patient, this barrier is broken and thecontents of the gut leak out into surroundingareas. The research team in UCD Conway useda model of IBD and, by applying a new class ofdrugs known as hydroxylase inhibitors, wereable to almost completely reverse thesymptoms of the disease.

“When we applied these new drugs to our IBDmodel, the gut was tricked into thinking that itwas being deprived of oxygen. This activatedprotective pathways, which in turn preventedthe death of the cells that line thegastrointestinal tract,” explained ProfessorTaylor. “Our pre-clinical trial data can nowinform the next phase Sigmoid Pharma productdevelopment pipeline”.

In addition to the product that is currently inphase II clinical studies, Sigmoid Pharma isdeveloping a LEDDS™-enabled formulation ofthe hydroxylase inhibitordimethyloxaloylglycine (DMOG) to bring abouteffective, safe and targeted delivery of thispotential therapeutic agent.

Conway collaborator scoops Irish Times Innovation Award

Conway researchers led by Dr. TaraMcMorrow and Professor Michael Ryan havesuccessfully secured €485,500 in funding aspart of an overall award to the SystemsBiology towards Novel Chronic KidneyDisease Diagnosis and Treatment (SysKid)consortium under the European Union FP7programme.

Syskid (www.SysKid.eu) was established tofurther our understanding of chronic kidney

disease (CKD) and improve patient treatment,with particular focus on CKD arising fromdiabetes and hypertension. The multi-disciplinary research consortium has 25partners (16 universities, 9 industry partners)from 15 countries and the project is due to runfor five years.

The UCD Conway team, including postdoctoralresearchers Dr. Craig Slattery and Dr. NataliaMartin, will utilise cell culture and animal

models to identify processes involved in earlyCKD progression and investigate novelstrategies for preventing and slowing theprogression of the disease. These studies willbe integrated with clinical and epidemiologicalstudies across the consortium using systemsbiology methodologies in order to develop newdiagnostic strategies and treatment options toprevent CKD development. [email protected] for details of a PhDposition currently available.

Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Meta-analysis by UCD researchers led byConway Fellow, Professor Denis Shields hasdetermined that there is no clear evidencethat particular defective viral sequences inthe HIV-1 nef gene or certain regions of theprotein play a significant role in diseaseprogression.

HIV-infected patients can be categorised onthe basis of the number of years it takes forthem to progress to AIDS. Some patientsmaintain stable CD4 lymphocyte counts anddo not go on to develop AIDS even after morethan 10 years of infection.

Scientists are curious as to why these long-term, non- progressor (LTNP) patients do notdevelop AIDS. This may reflect differences inthe host, viral genetics or environmentalfactors that could potentially be exploited forthe treatment of the disease.

Studies in model organisms have shown thatinfection with nef-deficient virus shows anattenuated course of infection and some

studies in humans have shown that nonprogression was associated with grossdeletions in the nef gene.

However, much of the research in the area todate has been based on observational or casestudies rather than rigorous, systematicscientific evaluation. This work by doctoralcandidate Ravindra Pushker set out todetermine in a substantially larger sample setif any association exists between diseaseprogression and particular amino aciddifferences or deletions within the nef gene.

On a per patient basis, there was no excess ofLTNP patients with one or more defective nefsequences when compared to progressors.While the high frequency of amino acidreplacement at particular residues is indicativeof rapid evolvement, permutation testingshowed that residues with more replacementsthan expected were not statistically significant.

The researchers conclude that current dataprovides no evidence that individual residues

of HIV nef are critical in determining the rateof disease progression. Professor DenisShields believes that searches for modifiers ofprogression rates should now focus on otherhost and viral factors. “Systematic evaluationof large quantities of data by bioinformaticscan be just as important in refutinghypotheses that are current in the literature, asit is in discovering unknown patterns”, he said.

This research was funded through ScienceFoundation Ireland and University CollegeDublin.

Reference:Meta-analysis to test the association of HIV-1 nef aminoacid differences and deletions with disease progression.Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields.Journal of Virology, Apr 2010 p3644-3653

GlycoExtractor advances glycan data manipulation

Glycomics needs the supporting frameworkof extensive, well-curated databases andflexible analytical tools. Currently, this fieldof study lacks the established,comprehensive and centralised datacollections, standards and informationreporting protocols that exist withingenomics and proteomics.

Researchers, Dr Natalia Artemenko and DrMatthew Campbell from the National Instituteof Bioprocessing Research & Training (NIBRT)led by Conway Fellow, Professor Pauline Ruddhave developed an open access, web-basedinterface that facilitates extraction, queryingand sharing of HPLC-glycan data generated inhigh throughput processes.

Glycosylation is the most common andstructurally diverse post-translationalmodification of proteins. More than half of allgene products have been shown to beglycosylated. With many specific glycans orglycoforms showing potential as cancerbiomarkers, there is an increasing need todevelop high throughput, highly sensitive androbust strategies that detail the glycome of

cells, tissues and fluids.

Commercial packages that support HPLCinstruments cannot facilitate the extraction oflarge quantities of data. In an effort to alleviatethis bottleneck within high-throughputglycomic projects, the NIBRT team havedeveloped a web-based tool that interfaceswith the Waters chromatography softwarepackage to improve and automate the exportof data to various file formats for subsequentanalysis. The modular architecture of the toolalso facilitates the manipulation of data fromother data management systems.

The NIBRT team are now working to integrateGlycoExtractor with the EUROCarbDBframework to provide a comprehensive high-throughput HPLC data analysis platform forthe storage and annotation of experimentaldata. The integration of next generationbioinformatic tools will further thedevelopment of unified approaches forhandling large scale glycomics data initiativeswith applications in biomarker discovery

This research was partially supported by

EUROCarbDB, a research infrastructure designstudy funded by the EU 6th FrameworkProgramme. Prospective users can access theGlycoExtractor tool onhttp://glycobase.nibrt.ie:8080/DemoGlycoExtractor/mainPage.ReferenceGlycoExtractor: A web-based interface for highthroughput processing of HPLC-Glycan dataNatalia V. Artemenko, Matthew P. Campbell, and PaulineM. Rudd Journal of Proteome Research, 2010, 9 (4), pp2037–2041

NIBRT researchers Dr Matthew Campbell and Dr NataliaArtemenko who developed GlycoExtractor

Zebrafish model gives insights into diabetic blindness

New research led by Conway Fellow DrBreandán Kennedy indicates that treatmentof diabetic blindness should look atprotecting the neurons responsible for colourvision in the eye and not just targeting theblood vessels as is currently the practice.

Nearly 2.5 million people worldwide are blinddue to diabetic retinopathy. This secondarycomplication of diabetes activates the growthof new leaky blood vessels in the eye and isresponsible for the death of photoreceptors,the neurons that send visual messages to ourbrain.

Until now, it was unclear if the changes tovessels and neurons occurred independently ofone other and which type of retinal neuron is

most likely to die as a result of the raisedglucose levels seen in diabetes.

Dr Kennedy and his team found that new bloodvessels and the neuronal cell death in diabeticretinopathy can arise independently of eachother. In addition, they identified that conephotoreceptor neurons, those involved incolour vision and used in daylight, are mostaffected by the high glucose levels.

The research team made their observationsusing a novel zebrafish model of diabetes,which resembles the early stages of diabeticretinopathy in humans. It is an excitingdevelopment for the group who now hope tofurther extend their research and establish amodel of late stage diabetic disease.

Commenting on the research, Dr Kennedysaid, “By establishing a robust model for earlyand late stage diabetic retinopathy, we wouldhope to better understand the progression ofthe disease and pave the way for identifyingnew drug targets for its successful treatment”.

The research was funded through ScienceFoundation Ireland and the Health ResearchBoard.

Reference:

Predominant cone photoreceptor dysfunction in ahyperglycaemic model of non-proliferative diabeticretinopathy. Yolanda Alvarez, Jenneth Chen, AlisonReynolds, Nore Waghorne, John J. O’Connor, BreandanKennedy. Disease Models & Mechanisms (2010)

May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3

New guide to data interpretation

Western blotting is a widely used technique to detect specific proteins. Although considered a semi-quantitative method, the results are often interpreted quantitatively. Scientific articles often do not specify how researchers quantified their results and how they compared biological replicates for statistical testing.

Conway Fellow, Prof Boris Kholodenko and his team in Systems Biology Ireland have described how results of statistical testing applied to western blot data are affected by the choice of normalisation strategy applied to the data. They have created a step-by-step guide to help scientists choose the most appropriate normalisation strategy for their particular study.

Normalisation strategies transform or manipulate data to allow quantitative comparison of biological replicates. The Kholodenko group used mathematical models to simulate the effects of normalisation and actual experimental data to corroborate the results.

“We clarified the quantitative use of western blot data and how the normalisation strategy applied to the data affects the statistical testing, possibly increasing false positives or false negatives”, explained Dr Andrea Degasperi from the Kholodenko group.

Western blotting provides experimental evidence that supports a given hypothesis

and is also used to validate data obtained from other techniques. Clarifying its quantitative use for decision making or statistical testing is necessary.

The Kholodenko group hope their study findings will not only act as a reference for scientists but also encourage them to include this critical information about data interpretation in published articles.

Reference Degasperi A et al. Evaluating Strategies to Normalise Biological Replicates of Western Blot Data. PLoS ONE, 9(1): e87293. doi:10.1371/journal.pone.0087293, 2014.

Enabling research and innovation projectsIrish biopharmaceutical developmentcompany, Sigmoid Pharma recently scoopedthe overall Innovation of the Year award atthe inaugural Irish Times All-IslandInnovation Awards. The life-science SME,founded by UCD pharmacology graduate, DrIvan Coulter, has actively collaborated withConway Fellow, Professor Cormac Taylorsince being granted a Science FoundationIreland industry research partnership awardin 2004.

The Irish Times award recognises the stellarinnovative performance of Sigmoid Pharma intheir application of research and development.The company has developed two new drugtechnologies, LEDDS™ and SmPill™, which notonly enhance the solubility and permeability ofthe drug but can deliver it to targeted locationsin the gastrointestinal tract, including thecolon.

The Sigmoid Pharma-Taylor collaboration isfacilitating the development of a newtherapeutic approach for the treatment ofinflammatory bowel disease (IBD) by bringingtogether the research methodology of theTaylor group with the proprietaryliquid/emulsion drug delivery system,LEDDS®, developed by Sigmoid Pharma.

Commenting on the award, Professor Taylorsaid, “We are delighted for Dr Coulter and histeam and indeed it reflects well on ourpartnership. A key driver of successfulscientific research in 2010 is meaningfulinteraction of academia with industry that

results in both academic outputs and theapplication of research toward clinical productdevelopment with indigenous companies.”

Commenting on the Taylor collaboration, DrCoulter said, “The collaboration with the Taylorlaboratory clearly demonstrates the potentialthat can be realised through focusedapplication of basic research. The developmentof a smart economy will depend on like-mindedcollaborative partners identifying opportunitiesand realising basic and applied researchsynergies. This collaboration, initiated througha SFI research supplement, highlights thepotential that innovative indigenous companiesworking with academia can realise.”

Taylor’s collaboration with Sigmoid Pharma hascertainly been successful by these metrics withthree co-authored publications to date in two ofthe highest ranking scientific journals in thefield, Gastroenterology and Proceeding of theNational Academy of Sciences, as well as thegeneration of proprietary innovative productsand the creation of high-skilled jobs.

More than 15,000 people in Ireland andmillions of people worldwide are living with thesymptoms IBD today. Current therapeuticoptions for this chronic debilitating disease arevery limited with surgery often being the onlyviable option. The Sigmoid product, currentlyin a phase II clinical study, uniquely enablesoral delivery of a powerful drug withoutcausing systemic side-effects.

Under normal conditions, the gastrointestinal

tract is lined with cells that block the contentsof the gut from leaking into the intestine. In anIBD patient, this barrier is broken and thecontents of the gut leak out into surroundingareas. The research team in UCD Conway useda model of IBD and, by applying a new class ofdrugs known as hydroxylase inhibitors, wereable to almost completely reverse thesymptoms of the disease.

“When we applied these new drugs to our IBDmodel, the gut was tricked into thinking that itwas being deprived of oxygen. This activatedprotective pathways, which in turn preventedthe death of the cells that line thegastrointestinal tract,” explained ProfessorTaylor. “Our pre-clinical trial data can nowinform the next phase Sigmoid Pharma productdevelopment pipeline”.

In addition to the product that is currently inphase II clinical studies, Sigmoid Pharma isdeveloping a LEDDS™-enabled formulation ofthe hydroxylase inhibitordimethyloxaloylglycine (DMOG) to bring abouteffective, safe and targeted delivery of thispotential therapeutic agent.

Conway collaborator scoops Irish Times Innovation Award

Conway researchers led by Dr. TaraMcMorrow and Professor Michael Ryan havesuccessfully secured €485,500 in funding aspart of an overall award to the SystemsBiology towards Novel Chronic KidneyDisease Diagnosis and Treatment (SysKid)consortium under the European Union FP7programme.

Syskid (www.SysKid.eu) was established tofurther our understanding of chronic kidney

disease (CKD) and improve patient treatment,with particular focus on CKD arising fromdiabetes and hypertension. The multi-disciplinary research consortium has 25partners (16 universities, 9 industry partners)from 15 countries and the project is due to runfor five years.

The UCD Conway team, including postdoctoralresearchers Dr. Craig Slattery and Dr. NataliaMartin, will utilise cell culture and animal

models to identify processes involved in earlyCKD progression and investigate novelstrategies for preventing and slowing theprogression of the disease. These studies willbe integrated with clinical and epidemiologicalstudies across the consortium using systemsbiology methodologies in order to develop newdiagnostic strategies and treatment options toprevent CKD development. [email protected] for details of a PhDposition currently available.

Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Meta-analysis by UCD researchers led byConway Fellow, Professor Denis Shields hasdetermined that there is no clear evidencethat particular defective viral sequences inthe HIV-1 nef gene or certain regions of theprotein play a significant role in diseaseprogression.

HIV-infected patients can be categorised onthe basis of the number of years it takes forthem to progress to AIDS. Some patientsmaintain stable CD4 lymphocyte counts anddo not go on to develop AIDS even after morethan 10 years of infection.

Scientists are curious as to why these long-term, non- progressor (LTNP) patients do notdevelop AIDS. This may reflect differences inthe host, viral genetics or environmentalfactors that could potentially be exploited forthe treatment of the disease.

Studies in model organisms have shown thatinfection with nef-deficient virus shows anattenuated course of infection and some

studies in humans have shown that nonprogression was associated with grossdeletions in the nef gene.

However, much of the research in the area todate has been based on observational or casestudies rather than rigorous, systematicscientific evaluation. This work by doctoralcandidate Ravindra Pushker set out todetermine in a substantially larger sample setif any association exists between diseaseprogression and particular amino aciddifferences or deletions within the nef gene.

On a per patient basis, there was no excess ofLTNP patients with one or more defective nefsequences when compared to progressors.While the high frequency of amino acidreplacement at particular residues is indicativeof rapid evolvement, permutation testingshowed that residues with more replacementsthan expected were not statistically significant.

The researchers conclude that current dataprovides no evidence that individual residues

of HIV nef are critical in determining the rateof disease progression. Professor DenisShields believes that searches for modifiers ofprogression rates should now focus on otherhost and viral factors. “Systematic evaluationof large quantities of data by bioinformaticscan be just as important in refutinghypotheses that are current in the literature, asit is in discovering unknown patterns”, he said.

This research was funded through ScienceFoundation Ireland and University CollegeDublin.

Reference:Meta-analysis to test the association of HIV-1 nef aminoacid differences and deletions with disease progression.Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields.Journal of Virology, Apr 2010 p3644-3653

GlycoExtractor advances glycan data manipulation

Glycomics needs the supporting frameworkof extensive, well-curated databases andflexible analytical tools. Currently, this fieldof study lacks the established,comprehensive and centralised datacollections, standards and informationreporting protocols that exist withingenomics and proteomics.

Researchers, Dr Natalia Artemenko and DrMatthew Campbell from the National Instituteof Bioprocessing Research & Training (NIBRT)led by Conway Fellow, Professor Pauline Ruddhave developed an open access, web-basedinterface that facilitates extraction, queryingand sharing of HPLC-glycan data generated inhigh throughput processes.

Glycosylation is the most common andstructurally diverse post-translationalmodification of proteins. More than half of allgene products have been shown to beglycosylated. With many specific glycans orglycoforms showing potential as cancerbiomarkers, there is an increasing need todevelop high throughput, highly sensitive androbust strategies that detail the glycome of

cells, tissues and fluids.

Commercial packages that support HPLCinstruments cannot facilitate the extraction oflarge quantities of data. In an effort to alleviatethis bottleneck within high-throughputglycomic projects, the NIBRT team havedeveloped a web-based tool that interfaceswith the Waters chromatography softwarepackage to improve and automate the exportof data to various file formats for subsequentanalysis. The modular architecture of the toolalso facilitates the manipulation of data fromother data management systems.

The NIBRT team are now working to integrateGlycoExtractor with the EUROCarbDBframework to provide a comprehensive high-throughput HPLC data analysis platform forthe storage and annotation of experimentaldata. The integration of next generationbioinformatic tools will further thedevelopment of unified approaches forhandling large scale glycomics data initiativeswith applications in biomarker discovery

This research was partially supported by

EUROCarbDB, a research infrastructure designstudy funded by the EU 6th FrameworkProgramme. Prospective users can access theGlycoExtractor tool onhttp://glycobase.nibrt.ie:8080/DemoGlycoExtractor/mainPage.ReferenceGlycoExtractor: A web-based interface for highthroughput processing of HPLC-Glycan dataNatalia V. Artemenko, Matthew P. Campbell, and PaulineM. Rudd Journal of Proteome Research, 2010, 9 (4), pp2037–2041

NIBRT researchers Dr Matthew Campbell and Dr NataliaArtemenko who developed GlycoExtractor

Zebrafish model gives insights into diabetic blindness

New research led by Conway Fellow DrBreandán Kennedy indicates that treatmentof diabetic blindness should look atprotecting the neurons responsible for colourvision in the eye and not just targeting theblood vessels as is currently the practice.

Nearly 2.5 million people worldwide are blinddue to diabetic retinopathy. This secondarycomplication of diabetes activates the growthof new leaky blood vessels in the eye and isresponsible for the death of photoreceptors,the neurons that send visual messages to ourbrain.

Until now, it was unclear if the changes tovessels and neurons occurred independently ofone other and which type of retinal neuron is

most likely to die as a result of the raisedglucose levels seen in diabetes.

Dr Kennedy and his team found that new bloodvessels and the neuronal cell death in diabeticretinopathy can arise independently of eachother. In addition, they identified that conephotoreceptor neurons, those involved incolour vision and used in daylight, are mostaffected by the high glucose levels.

The research team made their observationsusing a novel zebrafish model of diabetes,which resembles the early stages of diabeticretinopathy in humans. It is an excitingdevelopment for the group who now hope tofurther extend their research and establish amodel of late stage diabetic disease.

Commenting on the research, Dr Kennedysaid, “By establishing a robust model for earlyand late stage diabetic retinopathy, we wouldhope to better understand the progression ofthe disease and pave the way for identifyingnew drug targets for its successful treatment”.

The research was funded through ScienceFoundation Ireland and the Health ResearchBoard.

Reference:

Predominant cone photoreceptor dysfunction in ahyperglycaemic model of non-proliferative diabeticretinopathy. Yolanda Alvarez, Jenneth Chen, AlisonReynolds, Nore Waghorne, John J. O’Connor, BreandanKennedy. Disease Models & Mechanisms (2010)

May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3

Five research projects led by Conway Fellows in areas of key priority for Ireland have secured funding under the Science Foundation Ireland (SFI) Investigator programme recently announced by Ministers Richard Bruton and Sean Sherlock. Funding for each project ranges from €860,000 to €1.9 million over a three to five year period.

Prof Seamas Donnelly will tackle the treatment of Pseudomonas aeruginosa infection that is common in patients with cystic fibrosis. During infection, Pseudomonas clump together to form sticky aggregates that develop into a biofilm, making them more difficult to treat with antibiotics.

“This funding award will allow us to develop new therapies to prevent biofilm formation in patients and make the bacteria responsible easier to treat with antibiotics. We also hope to develop a test that will identify those patients most likely to respond best to this new treatment”, said Prof Donnelly.

Prof Ken Wolfe will investigate the sexual reproduction cycles of three yeast species of economic importance. Pachysolen tannophilus is a potential bioethanol producer - this valuable natural fuel source also has uses in the cosmetic and other manufacturing industries. Hansenula polymorpha and Pichia pastoris are widely used in the biotechnology industry to express recombinant proteins such as pharmaceuticals.

The project will characterise how these species undergo mating-type switching. This is a natural process in which a yeast cell changes or switches ‘gender’ and, as a switched cell, it can mate with a cell that has not switched.

“When we understand the mechanism of switching, we should be able to modify the genomes to prevent switching from happening. This will open up the possibility of using powerful methods of genetic analysis to improve the production characteristics of these industrial yeasts with consequent economic benefits”, explained Prof Wolfe.

Prof Mark Crowe is undertaking a collaborative project with Prof Michael Diskin from Teagasc to develop early non-invasive and reliable molecular biomarkers of pregnancy in dairy cattle. Reproductive performance in dairy cattle is an important factor affecting production and economic efficiency particularly in seasonal grass-based systems such as in Ireland.

“We intend to improve on current commercial methods of pregnancy detection by producing a reliable early pregnancy test that can diagnose within 21 days of artificial insemination. This would be a major advance in the reproductive management of dairy herds as current detection limits are between days 28 -30 of pregnancy”, explained Prof Crowe.

Prof Patrick Lonergan has been awarded funding to reduce embryo mortality through improved understanding of embryo maternal communication. Prof Stefan Oscarson intends to design, synthesise and develop carbohydrate–based vaccines, therapeutics, diagnostics, and medical devices.

Commercialisation award for novel technology

Dr David O’Connell has patented a novel affinity tag technology providing a platform for the development of a suite of reagents and product applications for the biotechnology industry. He received funding under the Enterprise Ireland Commercialisation Fund 2014 to support the development and optimisation of a protein purification kit.

The fund will support the establishment of a start-up company, BlackLabBio, to commercialise this product and subsequent products incorporating the patented technology. The product will provide significant benefits of enhanced speed, simplicity and performance by reducing process steps involved in protein purification and biosensor display.

Irish biopharmaceutical developmentcompany, Sigmoid Pharma recently scoopedthe overall Innovation of the Year award atthe inaugural Irish Times All-IslandInnovation Awards. The life-science SME,founded by UCD pharmacology graduate, DrIvan Coulter, has actively collaborated withConway Fellow, Professor Cormac Taylorsince being granted a Science FoundationIreland industry research partnership awardin 2004.

The Irish Times award recognises the stellarinnovative performance of Sigmoid Pharma intheir application of research and development.The company has developed two new drugtechnologies, LEDDS™ and SmPill™, which notonly enhance the solubility and permeability ofthe drug but can deliver it to targeted locationsin the gastrointestinal tract, including thecolon.

The Sigmoid Pharma-Taylor collaboration isfacilitating the development of a newtherapeutic approach for the treatment ofinflammatory bowel disease (IBD) by bringingtogether the research methodology of theTaylor group with the proprietaryliquid/emulsion drug delivery system,LEDDS®, developed by Sigmoid Pharma.

Commenting on the award, Professor Taylorsaid, “We are delighted for Dr Coulter and histeam and indeed it reflects well on ourpartnership. A key driver of successfulscientific research in 2010 is meaningfulinteraction of academia with industry that

results in both academic outputs and theapplication of research toward clinical productdevelopment with indigenous companies.”

Commenting on the Taylor collaboration, DrCoulter said, “The collaboration with the Taylorlaboratory clearly demonstrates the potentialthat can be realised through focusedapplication of basic research. The developmentof a smart economy will depend on like-mindedcollaborative partners identifying opportunitiesand realising basic and applied researchsynergies. This collaboration, initiated througha SFI research supplement, highlights thepotential that innovative indigenous companiesworking with academia can realise.”

Taylor’s collaboration with Sigmoid Pharma hascertainly been successful by these metrics withthree co-authored publications to date in two ofthe highest ranking scientific journals in thefield, Gastroenterology and Proceeding of theNational Academy of Sciences, as well as thegeneration of proprietary innovative productsand the creation of high-skilled jobs.

More than 15,000 people in Ireland andmillions of people worldwide are living with thesymptoms IBD today. Current therapeuticoptions for this chronic debilitating disease arevery limited with surgery often being the onlyviable option. The Sigmoid product, currentlyin a phase II clinical study, uniquely enablesoral delivery of a powerful drug withoutcausing systemic side-effects.

Under normal conditions, the gastrointestinal

tract is lined with cells that block the contentsof the gut from leaking into the intestine. In anIBD patient, this barrier is broken and thecontents of the gut leak out into surroundingareas. The research team in UCD Conway useda model of IBD and, by applying a new class ofdrugs known as hydroxylase inhibitors, wereable to almost completely reverse thesymptoms of the disease.

“When we applied these new drugs to our IBDmodel, the gut was tricked into thinking that itwas being deprived of oxygen. This activatedprotective pathways, which in turn preventedthe death of the cells that line thegastrointestinal tract,” explained ProfessorTaylor. “Our pre-clinical trial data can nowinform the next phase Sigmoid Pharma productdevelopment pipeline”.

In addition to the product that is currently inphase II clinical studies, Sigmoid Pharma isdeveloping a LEDDS™-enabled formulation ofthe hydroxylase inhibitordimethyloxaloylglycine (DMOG) to bring abouteffective, safe and targeted delivery of thispotential therapeutic agent.

Conway collaborator scoops Irish Times Innovation Award

Conway researchers led by Dr. TaraMcMorrow and Professor Michael Ryan havesuccessfully secured €485,500 in funding aspart of an overall award to the SystemsBiology towards Novel Chronic KidneyDisease Diagnosis and Treatment (SysKid)consortium under the European Union FP7programme.

Syskid (www.SysKid.eu) was established tofurther our understanding of chronic kidney

disease (CKD) and improve patient treatment,with particular focus on CKD arising fromdiabetes and hypertension. The multi-disciplinary research consortium has 25partners (16 universities, 9 industry partners)from 15 countries and the project is due to runfor five years.

The UCD Conway team, including postdoctoralresearchers Dr. Craig Slattery and Dr. NataliaMartin, will utilise cell culture and animal

models to identify processes involved in earlyCKD progression and investigate novelstrategies for preventing and slowing theprogression of the disease. These studies willbe integrated with clinical and epidemiologicalstudies across the consortium using systemsbiology methodologies in order to develop newdiagnostic strategies and treatment options toprevent CKD development. [email protected] for details of a PhDposition currently available.

Success in EU FP7 call

Bioinformatic analysis of HIV progression studies

Meta-analysis by UCD researchers led byConway Fellow, Professor Denis Shields hasdetermined that there is no clear evidencethat particular defective viral sequences inthe HIV-1 nef gene or certain regions of theprotein play a significant role in diseaseprogression.

HIV-infected patients can be categorised onthe basis of the number of years it takes forthem to progress to AIDS. Some patientsmaintain stable CD4 lymphocyte counts anddo not go on to develop AIDS even after morethan 10 years of infection.

Scientists are curious as to why these long-term, non- progressor (LTNP) patients do notdevelop AIDS. This may reflect differences inthe host, viral genetics or environmentalfactors that could potentially be exploited forthe treatment of the disease.

Studies in model organisms have shown thatinfection with nef-deficient virus shows anattenuated course of infection and some

studies in humans have shown that nonprogression was associated with grossdeletions in the nef gene.

However, much of the research in the area todate has been based on observational or casestudies rather than rigorous, systematicscientific evaluation. This work by doctoralcandidate Ravindra Pushker set out todetermine in a substantially larger sample setif any association exists between diseaseprogression and particular amino aciddifferences or deletions within the nef gene.

On a per patient basis, there was no excess ofLTNP patients with one or more defective nefsequences when compared to progressors.While the high frequency of amino acidreplacement at particular residues is indicativeof rapid evolvement, permutation testingshowed that residues with more replacementsthan expected were not statistically significant.

The researchers conclude that current dataprovides no evidence that individual residues

of HIV nef are critical in determining the rateof disease progression. Professor DenisShields believes that searches for modifiers ofprogression rates should now focus on otherhost and viral factors. “Systematic evaluationof large quantities of data by bioinformaticscan be just as important in refutinghypotheses that are current in the literature, asit is in discovering unknown patterns”, he said.

This research was funded through ScienceFoundation Ireland and University CollegeDublin.

Reference:Meta-analysis to test the association of HIV-1 nef aminoacid differences and deletions with disease progression.Ravindra Pushker, Jean-Marc Jacquē, Denis C. Shields.Journal of Virology, Apr 2010 p3644-3653

GlycoExtractor advances glycan data manipulation

Glycomics needs the supporting frameworkof extensive, well-curated databases andflexible analytical tools. Currently, this fieldof study lacks the established,comprehensive and centralised datacollections, standards and informationreporting protocols that exist withingenomics and proteomics.

Researchers, Dr Natalia Artemenko and DrMatthew Campbell from the National Instituteof Bioprocessing Research & Training (NIBRT)led by Conway Fellow, Professor Pauline Ruddhave developed an open access, web-basedinterface that facilitates extraction, queryingand sharing of HPLC-glycan data generated inhigh throughput processes.

Glycosylation is the most common andstructurally diverse post-translationalmodification of proteins. More than half of allgene products have been shown to beglycosylated. With many specific glycans orglycoforms showing potential as cancerbiomarkers, there is an increasing need todevelop high throughput, highly sensitive androbust strategies that detail the glycome of

cells, tissues and fluids.

Commercial packages that support HPLCinstruments cannot facilitate the extraction oflarge quantities of data. In an effort to alleviatethis bottleneck within high-throughputglycomic projects, the NIBRT team havedeveloped a web-based tool that interfaceswith the Waters chromatography softwarepackage to improve and automate the exportof data to various file formats for subsequentanalysis. The modular architecture of the toolalso facilitates the manipulation of data fromother data management systems.

The NIBRT team are now working to integrateGlycoExtractor with the EUROCarbDBframework to provide a comprehensive high-throughput HPLC data analysis platform forthe storage and annotation of experimentaldata. The integration of next generationbioinformatic tools will further thedevelopment of unified approaches forhandling large scale glycomics data initiativeswith applications in biomarker discovery

This research was partially supported by

EUROCarbDB, a research infrastructure designstudy funded by the EU 6th FrameworkProgramme. Prospective users can access theGlycoExtractor tool onhttp://glycobase.nibrt.ie:8080/DemoGlycoExtractor/mainPage.ReferenceGlycoExtractor: A web-based interface for highthroughput processing of HPLC-Glycan dataNatalia V. Artemenko, Matthew P. Campbell, and PaulineM. Rudd Journal of Proteome Research, 2010, 9 (4), pp2037–2041

NIBRT researchers Dr Matthew Campbell and Dr NataliaArtemenko who developed GlycoExtractor

Zebrafish model gives insights into diabetic blindness

New research led by Conway Fellow DrBreandán Kennedy indicates that treatmentof diabetic blindness should look atprotecting the neurons responsible for colourvision in the eye and not just targeting theblood vessels as is currently the practice.

Nearly 2.5 million people worldwide are blinddue to diabetic retinopathy. This secondarycomplication of diabetes activates the growthof new leaky blood vessels in the eye and isresponsible for the death of photoreceptors,the neurons that send visual messages to ourbrain.

Until now, it was unclear if the changes tovessels and neurons occurred independently ofone other and which type of retinal neuron is

most likely to die as a result of the raisedglucose levels seen in diabetes.

Dr Kennedy and his team found that new bloodvessels and the neuronal cell death in diabeticretinopathy can arise independently of eachother. In addition, they identified that conephotoreceptor neurons, those involved incolour vision and used in daylight, are mostaffected by the high glucose levels.

The research team made their observationsusing a novel zebrafish model of diabetes,which resembles the early stages of diabeticretinopathy in humans. It is an excitingdevelopment for the group who now hope tofurther extend their research and establish amodel of late stage diabetic disease.

Commenting on the research, Dr Kennedysaid, “By establishing a robust model for earlyand late stage diabetic retinopathy, we wouldhope to better understand the progression ofthe disease and pave the way for identifyingnew drug targets for its successful treatment”.

The research was funded through ScienceFoundation Ireland and the Health ResearchBoard.

Reference:

Predominant cone photoreceptor dysfunction in ahyperglycaemic model of non-proliferative diabeticretinopathy. Yolanda Alvarez, Jenneth Chen, AlisonReynolds, Nore Waghorne, John J. O’Connor, BreandanKennedy. Disease Models & Mechanisms (2010)

May 2010.qxd:Layout 1 copy 07/05/2010 13:12 Page 3

In recognition of his outstanding contribution to chemistry, Prof Pat Guiry has been awarded the Boyle Higgins Gold Medal by the Institute of Chemistry in Ireland. The award involves a gold medal and a monetary sum to cover expenses for a lecture.

Conway Fellow, Prof Guiry, who was Institute director from 2004-2005, focuses on developing new catalysts and synthetic methodologies to prepare compounds of biological interest, particularly those with anti-inflammatory properties.

PhD student, Liam Collins (Rodriguez group) received a graduate student gold award at the 2014 Materials Research

Society (MRS) Spring Meeting in San Francisco. This award recognises graduate students whose academic achievements and current materials science research display a high level of excellence and distinction. Liam recently published research in Nature Communications.

PhD student, Aoife O’Gorman (Brennan group) won an award for the best early career oral presentation at the 2014 Analytical Tools for Cutting-edge Metabolomics conference; a joint meeting of the Analytical Division of the Royal Society of Chemistry and the International Metabolomics Society held in London. Aoife recently published in the Journal of Chromatography B.

Recognising excellence

Patrick Hobbs (l), President of the Institute of Chemistry of Ireland presents Prof Pat Guiry with the Boyle-Higgins Gold Medal

Reference McGrogan B et al. Spindle assembly checkpoint protein expression correlates with cellular proliferation and shorter time to recurrence in ovarian cancer. Hum Pathol. 2014 Mar 27. pii: S0046-8177(14)00121-X. doi:10.1016/j.humpath.2014.03.004. [Epub ahead of print] PMID: 24792619.

estrogen receptor, this research suggests that high levels of PRDX1 may maintain responsiveness to this drug and improve patient survival.

These findings may have implications for breast cancer care in the future, as PRDX1 could be used as a biomarker to guide decisions regarding therapy. (publication pending in Breast Cancer Research)

Perinuclear MAD2 immunostaining in a moderately differentiated clear cell carcinoma (x40)

free survival irrespective of histological subtype could help guide clinicians as to whether chemotherapy will actually benefit the patient.”.