biomedical sciences research institute - Research - University of Ulster

BIOMEDICAL SCIENCESRESEARCH INSTITUTEANNUAL REPORT1 AUGUST 2007 - 31 JULY 2008

BIOMEDICAL SCIENCESRESEARCH INSTITUTEAnnual Report(1 August 2007 – 31 July 2008)CONTENTSPage No1. Foreword from the Pro Vice Chancellor (Research and Innovation) 2-32. Foreword from the Director of the Research Institute 4-103. Selected Achievements 11-134. Biomedical Genomics Research Group 14-195. Bioimaging Research Group 20-296. Cancer and Ageing Research Group 30-407. Diabetes Research Group 41-558. Microbiology & Biotechnology Research Group 56-699. Northern Ireland Centre for Food and Health (NICHE) 70-9110. Stem Cells and Epigenetics Research Group 92-9711. Systems Biology Research Group 98-10612. Vision Science Research Group 106-12513. Research Funding 126-13114. Research Students 132-1411

1 Foreword by the Pro Vice-Chancellor(Research and Innovation)It is the responsibility of any institution which conductsacademic research to do so in a way that makes a significantcontribution both to the social, political and cultural fabricof the community which it serves in particular and tosociety and the economy in general. In reading the annualreports from University of Ulster Research Institutes I amconfident that you will find the research undertaken atUlster to have more than fulfilled expectations over thepast year.The University’s growing reputation for high quality research has enabled usto continue to attract additional high-calibre research staff who have assistedcolleagues in attracting external research and other income and in completingwork that has led to highly prestigious papers, books and other key performanceoutputs.In particular, the University has had a successful year in terms of research grantincome with £11.5M of externally funded grants. The number of major externalawards, the value of which exceeds £200k, rose to eight with income totalling£3M attracted from prestigious Research Councils.In addition to the annual allocation of DEL postgraduate of £3.38M, this year,the University received just over £300k in support of 34 new DEL funded PhDstudentships to be held in research areas that have specific relevance to theNorthern Ireland economy; thus allowing further development of R&D talentessential for innovation in business and the public sector. This funding enablesUlster to support 244 full-time research students with a further 161 supportedfrom a range of other sources of funding.Research staff have made a significant contribution to Northern Ireland’s largestevery strategic review under the MATRIX programme. A number of colleaguescontributed significantly as members on the main panel with many other colleagueson Horizon panels across all five sectors, ie: Advanced Engineering (Transport),Advanced Materials, Agrifood, ICT and Life & Health Sciences. The MATRIXrecommendations are implemented under the leadership of DETI and MinisterArlene Foster and the University will play a significant role in implementing itsrecommendations and model.In November 2007 Ulster made its largest submission to the national ResearchAssessment Exercise (RAE2008). Almost 500 staff in 25 Units of ResearchAssessment participated in the exercise and a number of Ulster staff participatedin RAE Sub-Panels with two members of staff being asked to act as Chair (ProfessorHugh McKenna – Nursing and Midwifery and Professor Seamus MacMathuna –Celtic Studies).The RAE2008 outcomes will inform the future research strategy of the Universityand the University’s research strategy document (SUPPORTIVe: Strategy andAction Plan for Research, Research Training and Innovation 2006-2009) is to berevised during 2008/09.There continues to be a very strong flow of research findings coming out of ourresearch activities this year, many as new disclosures, adding to our intellectualproperty portfolio. We continue to exploit this asset through knowledge and2

technology transfer activities managed through our Office of Innovation.I trust that you will enjoy reading the Report and commend it to you as evidencethat University of Ulster research ranks highly amongst UK institutions.Professor ND BlackPro Vice Chancellor (Research & Innovation)3

2 Foreword by the Research InstituteDirector“An Outstanding Success in the ResearchAssessment Exercise (RAE2008)”The Biomedical Sciences Research Institute (BMSRI) undertakesstrategically focused research relating to the causes, diagnosis,prevention, and treatment of human degenerative diseases,especially those with a nutritional aspect.The BMSRI is the largest Institute within the University of Ulster and currentlyaccommodates more than 235 research staff/students. The Institute offers astate of the art research environment for high profile researchers to undertakeinternationally agenda setting research in strategically important prioritisedareas of biomedicine. Our focused research strategy is supported by extensiveand complementary multidisciplinary expertise, superb infrastructure andcontemporary core technologies. Particular areas of research strength includenutrition, genomics and proteomics of disease including personalized medicinerelating to Alzheimer’s Disease, diabetes, vision, arthritis and cancer.This strategically focused approach to research has, over the last decade, beenoutstanding amongst the University of Ulster’s successes, enabling us to be awardedthe top 5* ratings in both the 1996 and 2001 Research Assessment Exercises(RAE). In the most recent RAE (2008) our Biomedical Sciences submission wasin terms of Grade Point Average, second only to King’s College London andin terms of research power we were ranked number 1 out of 69 submissionsfrom across the UK (25% 4*; 35% 3*, 35 % 2*; 5 % 1*). A brief summary of oursubmission is provided in subsequent sections of this report.“I am delighted by this result and it is a pleasure to work with such talented researchers.This reflects the dedication, discipline, high standards and hard work of all our staff. Whilewe delight in this success, it is a bond that obliges us to yet higher achievement. Futurehigh success will be best fuelled and fostered in an atmosphere of high expectation andambition. We shall continue to review our research strategy, set new challenging goals,but embedded in a supportive environment with generous mentoring and selectivenurturing of the creative talent that is the oxygen for sustainable excellence. I am veryconfident for the future - I know that our talented scientists will rise to the challengesahead and grasp opportunities as they are presented, or create new opportunitieswhere they do not yet exist.”The Biomedical Sciences Research Institute strategy is:• above all, to undertake internationally agenda-setting research in focusedareas of biomedical science;• to disseminate and publish our research outputs in the highest quality peerreviewedjournals;• where appropriate, to protect intellectual property arising from research andfacilitate translation of basic and applied research into the clinically usefulproducts for patient benefit and drive economic growth regionally, nationallyand internationally;• to actively transfer knowledge and skills to the community and develop humancapital to enable a societal and economic return on investments;• to provide leadership, influence and establish meaningful networks regionally,nationally and internationally;• to promote a culture of innovation and creativity and establish a financiallysustainable research infrastructure to enable the BMSRI to grow and thrive.4

New exciting developments this year include the completion of our new £3.9MCentre for Metabolomics, sited opposite our Centre for Molecular Bioscience.This will bring together researchers from the Diabetes, Biomedical Genomicsand our developing Pharmaceutical Science & Practice Research Groups for thestudy of complex metabolic effects. It enables the concentration of our massspectrometry expertise, combined with a NMR laboratory for further study ofmetabolite molecular structure. Our new Pharmaceutical Science & PracticeResearch Group compliments and strengthens our pharmaceutical-based researchexpertise that is already embedded in our other research groups.Our new £2M Clinical Translational Research and Innovation Centre (C-TRIC)was completed in 2008. This centre of excellence is a new purpose-built facilitylocated on the Western Health and Social Care Trust’s Altnagelvin Hospital site.The 9,000 sq ft complex is jointly operated and financially supported by Invest NI,the Western Trust, Derry City Council and the University of Ulster. It will act asa flagship for attracting investment through research and innovation in healthcareto Northern Ireland. C-TRIC aims to better “connect” the University’s researchto the clinical and research expertise within the hospital sector to ensure thatour healthcare innovations have a meaningful impact in improving the generalhealth of patients.Professor Tony Bjourson. Email: aj.bjourson@ulster.ac.uk5

The BMSRI Research StructureThe BMSRI incorporates the following Centres of Excellence:Centre for Molecular Biosciences (CMB) - funded by the Northern Ireland Support Programme forUniversity Research (SPUR 1, £14.5M)Centre for Functional Genomics - funded through Invest Northern Ireland as part of the CEC Peace &Reconciliation programme (£2M).FEI Centre for Advanced Imaging - funded through SRIF3 programme (£1.8M).Centre for Metabolomics - funded through SRIF3 programme (£3.8M).All BMSRI research is conducted within the following Recognised Research Groups (RRG’s):Disease - Related Research Groups:NICHE, the Northern Ireland Centre for Food and Health is the largest Group, covering all aspects of nutritionalresearch, but with particular emphases on gastrointestinal effects, the biology of satiety, effects and mechanismsof action of micronutrients, the creation of nutritionally advanced foods, aspects of food safety and prevention ofinfection, and nutritional effects on exercise and physiology. CFG member.Cancer & Ageing Research Group, which regards cancer as (usually) an aspect of ageing. Direct research intoageing involves studies of Alzheimer disease, through transgenic rodent models and dietary studies, and of Wernersyndrome, a premature ageing disease. Cancer-related work encompasses aspect of DNA damage, repair, replicationand methylation, often with nutrition-related angles: particular aspects include studies of DNA metabolism at thesingle-cell and single-gene level, and through microarrays. One aspect of cancer therapy which has shown considerablepromise is the specific targeting of hypoxic tumour cells with drugs, that are only activated in these treatmentresistant cells. One line of research, initially intended to develop an improved form of gene therapy, has resulted ina successful spinoff company, Gendel, which despite its name now concentrates on a direct physiological method oftreating oesophageal cancer.CFG member.Diabetes Research Group, seeking to understand the pathological effects of diabetes through an analysis of themechanisms of pancreatic beta-cell dysfunction and insulin glycation; to discover new antidiabetic drugs by isolationof new compounds from natural sources, and especially by studying the antidiabetic actions of structurally modifiedpeptides; and by creating insulin-secreting surrogate cells suitable for unraveling the mechanisms of pancreatic beta cellfunction and dysfunction. The Diabetes Research Group is intimately related to its spin-off company, Diabetica, whichthis year has concluded a very promising licencing agreement with Amylin Pharmaceuticals, Inc. CFG member.Vision Science Research Group, working on visual electrophysiology (especially on functional characteristicsof the short wavelength visual system, and on cortical contribution to spatial vision); and on visual impairment(especially on limits to foveal and peripheral vision in diseased eyes, on optical and retinal changes with age, on ocularblood-flow associated with nutritional deficiencies, and on visual development in Down Syndrome and cerebralpalsy.Technique-Related Research GroupsBioimaging Research Group, incorporating the FEI Phillips Centre for Advanced Bioimaging. This Group has anoutstanding array of imaging instruments and software, partly for support of other Groups, and partly for researchinto their own areas of interest: toxicology of nanoparticles, brain regeneration, angiogenesis in wound healing and intumour neovascularisation, imaging of living cell surfaces at atomic resolution, and viral growth.Biomedical Genomics Research Group, applying molecular genomic techniques to tumor development andmetastasis; to hormone/receptor interactions, especially the role of vitamin D in cancer; and to identification ofunusual DNA structures involved in control mechanisms. CFG member.6

Microbial Biotechnology Research Group, concentrating on the exploitation of microorganisms fortherapeutic purposes, and on their diagnosis. Research priorities include the development of rapid molecular toolsare for diagnosis of the water-borne pathogen Cryptosporidium parvum; the genomic and proteomic studies ofthermophilic bacteria, and their use as sources of new enzymes and antibiotics; biofilm formation in cystic fibrosis;and the biosynthesis of organophosphonate compounds with biocidal activity. CFG member.The Group also undertakes research on small molecules from plants with the objective of developing novel drugs.The proteomics of rare human tumors and their cell lines are also of interest; as is a recent development into theinterrelationship of antimalarial and antiretroviral drugs.Stem Cells and Epigenetics Research Group, working on the identification and manipulation of lymphopoieticstem cells, and on the role of DNA imprinting in embryo development.Systems Biology Research Group, using the modern techniques of massive data processing and analysis,and image processing to cope with the equally massive amounts of data being generated by molecular biology andmicroscopy, and to create in silico models of biological processes.Biomedical Sciences Research InstituteThe BMSRI has of over 235 researchers in 9 Research Groups contributing to the:• Centre for Molecular Biosciences (CMB).• Centre for Functional Genomics (CFG).• FEI Centre for Advanced Imaging.• Centre for Metabolomics.7

BMSRI Core FacilitiesContact: Karen Coyles - email: km.coyles@ulster.ac.ukEach Core Facility is led by an Academic Champion and supported by dedicated research or technical staff. Thesecore facilities encompass all of the equipment and infrastructure utilised by all research groups within the BMSRI. Wealso welcome external companies who would wish to utilise this valuable resource on a consultancy or collaborativebasis.Bio-Imaging Core Facility• Histology lab with cryo-ultramicrotome and automatic tissue processor• Quanta 200 environmental SEM• Nova 200 Nanolab twin beam FIB/SEM with cryostage• Tecnai G2 Biotwin TEM• Atomic force microscope• 2-photon confocal microscope and four other confocals• 4 fluorescence microscopes with a wide range of image analysis software• PALM laser microdissection and capture microscopeSystems Biology Core Facility• 5 dual processor servers - provide Web services and content-management software, groupware,file and database services (Oracle Enterprise server 10G) as well as Grid services (Globus andCONDOR).• Large-scale computing - 64-way Itanium Altix 3700 supercomputer with 128GB of addressablememory and 8 TB of disk storage.Genomics & Proteomics Core Facilities• Extensive culture facilities including Cat II lab• An array of LC/MS systems including QTOF Ultima, ICP-MS, TSQ Quantum Ultra, Q-trap,GC/MS; LC/MS/MS; MALDI-TOF, Trace MS-EV70 mass spectrometers, NMR.• Vision and Microflow Pathfinder protein purification workstations• Gamma and Xray sources• Electrofusion apparatus• 16 thermocyclers plus 2 real-time PCR• 2 microarray scanners• Peptide and DNA synthesisers• Protein and DNA sequencers• Nanodrop spectrometerHuman Intervention Studies Unit (HISU) Core Facility• Residential suite with accommodation for up to 12 volunteers, kitchen for preparation of duplicate meals• Exercise suite with BodPod, ergometer, treadmill, ergospirometer, bone densitometer• Food sensory lab• Gastrointestinal laboratoryVision Core Facility• Eye clinics equipped with: Refractometers; Keratometer; Tonometers; Ophthalmometers; Fundus imagingcamera; Field analyser; Optical coherence tomographer.8

Research Assessment Exercise Submission Summary (RAE2008)Our submission described our research activities in biomedical science, nutrition and dietetics, and optometry.Our overall strategy has been to concentrate on degenerative diseases, including those with a nutritionalaspect, that affect an increasingly ageing population: with, therefore, considerable overlap between nutritionaland biomedical research. We have worked at all levels from the molecular to the whole human; we havesought to develop insights into disease development, and hence to prevention, diagnosis and therapy; and wehave ensured a wide audience for our findings. Our focused approach to research has, over the last decadeand more, been outstanding amongst the University of Ulster's successes, achieving 5* ratings in both the1996 and 2001 RAEs.In the current RAE period we have had a further increase in productivity, assisted by the opening in2003 of a major, 6,200 m 2 new facility, the £14.5 M Centre for Molecular Biosciences. This hasdramatically improved our research infrastructure, providing facilities for residential nutritional studies onhealthy volunteers that are among the best in the UK, and a wide variety of molecular, image-processing,optometric and systems biology tools. This in turn has led to further success, with the formation of Centresof Excellence in Functional Genomics (£2M), Advanced Biological Imaging (£1.8M) andMetabolomics (£3.9M). We have increased our income during the RAE period to over £21 M of newfunding for research projects, and increased our staff numbers from 46.6 to 60.75, recruiting permanent stafffrom centers of excellence across the world. The outstanding recruit is Prof Sakmann, Nobel laureate 1991,a long-standing collaborator with our Systems Biology group, who has taken a part-time post here afterretirement from Heidelberg.We have published research papers in major transdisciplinary journals and in international specialist journalsoutstanding in their fields (Amer. J. Clin. Nutr., Blood, Circulation, Diabetes, Invest. Opthalmol. Vision Sci., J. Natl.Cancer Inst., Lancet, Nature, Proc Natl. Acad. Sci USA, Science). We have established links with several majorindustrial partners, formed two flourishing spin-out companies, and have 49 patents granted, with 24 pending.Lastly, we have had substantial impact on the policies of the UK and Irish governments, and of the EU,especially in nutritional matters.The Unit comprises nine Research Groups, led by senior scientists with international reputations and extensiveexperience of managing research in their own fields; this provides a highly supportive framework for research.Nutrition & Dietetics form the largest Group: three other long-established Groups concentrate on specific healthproblems, in Cancer, Diabetes and Vision. The SPUR-driven expansion allowed the creation of a new Group,Systems Biology, which is technique- rather than disease-centred; it applies recent advances in computationalbiology to a wide range of biomedical problems. The success of this technique-driven approach led us to createadditional cross-cutting, enabling-technology Research Groups. Each of these concentrates on the application ofadvanced techniques – Bioimaging, Biomedical Genomics, Microbiology & Biotechnology, StemCells & Epigenetics – rather than on research into specific diseases.This new arrangement has promoted inter-group collaboration, through applying specialist techniques to particularareas: interdisciplinary collaboration is widespread, with research into, for instance, anti-diabetic and anti-oncogenicaspects of nutrition, the systems biology of cancer, the genomics of vitamin receptors and of malignancy, imagingof DNA damage, the interaction between glucose metabolism and dementia, and the involvement of stem cells inoncogenesis.The main thrust of research is intended to continue along the lines that we have followed with success, concentrating onage-dependent degenerative diseases, with a major emphasis on their nutritional aspects. An important considerationin our strategy will be the achievement of the appropriate balance between reinforcing our existing strengths, andtaking advantage of new opportunities: the wise course being to exploit new opportunities that complement olderstrengths, as we have recently done by investing heavily in systems biology and functional genomics.Two major initiatives now underway can be relied on to provide major augmentations of research infrastructure: theSRIF3 1,250 m 2 Centre for Metabolomics which will provide advanced techniques in mass spectroscopy, nuclearmagnetic resonance, and bioinformatics analysis to research in nutritional areas and degenerative diseases such asdiabetes.. The Centre will be in the same building as the University’s new Pharmacy department. This juxtaposition9

of Metabolomics, pharmacy, nutrition and genomics will offer considerable opportunities for research themes inpersonalised medicine. Also, the Wellcome Trust is funding the Northern Ireland Clinical Research Facility(£6 M): which is a partnership between the University of Ulster (30%) and Queen’s University Belfast (70%). Thiscentre, to be part of the Royal Group of Hospitals Trust in Belfast, will focus on nutrition and metabolism, visionscience and cancer. These topics are highly congruent with our research programmes, and will provide us with greatlyenhanced interactions with clinical researchers.We are planning four strategic initiatives that will build on our existing strengths: creation of an eye bank for visionscience; the study of nanoparticle fate and toxicity; identification of biomarkers for the detection of pathogens, andsystems-biological investigations of new dietary strategies. Three other initiatives in progress may, if successful, alsoreinforce our research effort: an Ulster-Connacht Medical School, a cross-border initiative with NUI Galway,which would obviously strengthen our links with the Ulster medical community. It is proposed to create in AltnagelvinHospital, Derry, the Academic Business Clinical Research Innovation Facility (ABC-RIF): estimated at£1.9 M. This will provide laboratory workspace to enable the University and the Hospital Trust to carry out clinicalresearch. Lastly, the Irish Development Agency proposal currently under discussion involves the creationin Londonderry of ABIC, an Advanced Biological Imaging Centre, as a North-South collaboration. This willexploit existing regional expertise in telecommunications and medical devices.10

3. BIOMEDICAL SCIENCES RESEARCH INSTITUTE (BMSRI)Selected Achievements 2007/083rd Professor becomes Member of the Royal Irish AcademyProfessor Helene McNulty (pictured left) became the third member of BMSRIstaff to be elected as a Member of the Royal Irish Academy. Helene joinedher colleagues, Professor Peter Flatt and Professor Sean Strain, as a memberof Ireland’s most distinguished learned society.Nicholas Canny, President of the Royal Irish Academy (centre) welcoming Professor Helene McNulty and ProfessorRobert Welch to membership of the Royal Irish AcademyNobel Prize-Winning Scientist Joins the BMSRINobel Prize-winning scientist Professor Bert Sakmann (pictured right), whose ground-breaking work is admired by theworld’s neuroscience community, was appointed to a staff position within the BMSRIin December 2007. Professor Sakmann is one of the world’s most distinguishedbiomedical scientists, having been awarded the 1991 Nobel Prize for Physiology (withresearch partner Erwin Neher) for their discoveries concerning the function of singleion channels in cells.In October 2008, he delivered a special public lecture (entitled: “Decision-making:anatomy and physiology in the cerebral cortex”), to mark his tenure as Professor ofBiomedical Sciences at Ulster.The Vice Chancellor, Professor Richard Barnett, told theaudience that: “the decision by this most distinguished Nobel Prizewinningscientist to join us consolidates our international reputation for excellence in biomedical science.”News ReleaseProfessor Sakmann is currently involved in a research project on the nature of nerve cells, which is being jointlyconducted by the BMSRI and the prestigious Max Planck Institute for Neurobiology in Munich. He is collaboratingclosely with Dr Kurt Saetzler, his former PhD student and postdoctoral research fellow, who has been Lecturer inComputational Biology at Ulster since 2003.Awards for Ground-Breaking Ulster ScientistsProfessor Peter Flatt and Dr Victor Gault (pictured left) won prestigious awardsin recognition of their cutting-edge research into diabetes. Their Awards werepresented at the Diabetes UK Annual Professional Conference in Glasgow.Dr Gault received the Young Investigator Award for outstanding contributionto diabetes research. This highly competitive award, in recognition of youngscientists’ efforts and innovations aimed at improving understanding of diabetes,is supported by Cambridge University NHS Foundation Trust and is given inmemory of the highly renowned diabetes researcher Professor Charles Nicholas Hales.Professor Flatt was recipient of the Dorothy Hodgkin Lecture Award in recognition of his international contributionto research in the field of diabetes. This is one of Diabetes UK’s highest honours in memory of the late DorothyCrowfoot Hodgkin OM FRS (1910–1994), a Nobel Prize winner, who was described as one of the most outstandingscientists – and personalities – of the 20th century.11

BMSRI Academic Heads new Regional Network for the Alzheimer’s Research TrustThe Alzheimer’s Research Trust (ART), a major UK Charity for dementia research,provided funding of £95,000 to fund the establishment of a Northern Ireland Networkfor Alzheimer’s research.The new Network (which joins 15 other networks around the UK) is a partnershipbetween the University of Ulster and QUB, and Dr Christian Hölscher (Senior Lecturerin Neurosciences at Ulster) and Dr Janet Johnston (Psychiatry and Neuroscience atQUB) have been appointed as the joint coordinators of this Network.The coordinators view this Network as a very positive development for researchinto Alzheimer’s disease in Northern Ireland and believe that the major fundingprovided by the ART represents national recognition of the region’s research effortsin terms of dementia research. The Network will help to foster links between localresearchers, those in the UK and international counterparts.LtoR) Lady Sylvia Hermon MP with DrJanet Johnston, Marie Janson and DrChristian Hölscher at the official launchof the ART Northern Ireland Network(Belfast Castle, February 2008)European Life Sciences Enterprise AccoladeThree BMSRI researchers scooped a top prize in a pan-European enterprise competition that rewardsexperts who turn research into tangible products.Academic entrepreneurs Dr Neville McClenaghan, Professor Peter Flatt and Professor FinbarrO’Harte, who established University spin-out company Diabetica Ltd in 2004, won the inauguralACES Academic Enterprise Award 2008 for innovation in Life Sciences at a ceremony in Stockholm.The trio was given the accolade in recognition of their success in translating their research advances in tacklingdiabetes, obesity and related metabolic conditions into high-value commercial opportunities through Diabetica.Distinguished Fellowship Awards for BMSRI staff:Several members of BMSRI staff received awards at the Winter Graduation ceremony in December 2007.Professor Roger Marchant was awarded a Senior Distinguished Research Fellowship, in recognition of his outstandingcontribution to research in the field of microbial biotechnology in a career spanning more than 42 years. During thattime, he has held various senior posts including Head of Department of Biology and Head of the Research GraduateSchool for the Faculty of Life and Health Sciences.Dr Tara Moore (pictured right) was awarded a Distinguished Research Fellowship in recognitionof her work to alleviate a number of illnesses of the human visual system (in particular, dry-eyesyndrome). Dr Moore was a previous recipient of a University Distinguished Teaching Award andof a UK National Teaching Fellowship.Dr Stephen McClean, Lecturer in Proteomics (along with colleagues Dr Paul Hagan and DrDavid Ruddick) received a Distinguished Teaching Fellowship (Team Award) in recognition oftheir efforts to implement a number of newand innovative strategies to develop the undergraduate learning experience. This Team has soughtto bring the fundamentals of chemistry to life using recognizable and relevant examples and inso doing introduce a level of enjoyment to lectures, large group activities, and demonstrations.Dr Tara Moore12

Development of Ground-breaking Clinical Translational Research & Innovation Centre(C-TRIC)During 2007/08, the BMSRI became one of the leading drivers in the developmentof a new Clinical Translational Research & Innovation Centre (C-TRIC) at theAltnagelvin Hospital site.This unique project involves a joint partnership between the University, theWestern Health and Social Care Trust, and Derry City Council, bringing health,education and business under one roof.The development will support research and innovation and generate commercialopportunities in the region; it will also link the University’s research to the clinicalexpertise within the Western Trust; and focus on improving the general health andwell-being of the 290,000 people living in the Western region.This new facility will provide specialist workspace and services for academicPaul Mc Lean, FB Mc Kee Contractors, Derry researchers, clinical researchers and the biotechnology industry, including theCity Council Mayor, Alderman Drew Thompson, pharmaceutical, bio-pharmaceutical and medical device sectors.Elaine Way, Chief Executive Western Trust andProfessor Hugh McKenna, University of Ulsterbreak ground for the new C-TRIC facility atAltnagelvinResearch Could Lead to Cataract Treatment BreakthroughResearch by University of Ulster academic Professor Barbara Pierscionek (pictured right) could lead toa major breakthrough in the treatment of cataracts - a leading cause of sight problems and one of themost common forms of blindness in the world.Professor Pierscionek, in collaboration with two colleagues from the University of Texas at Arlington,Professor Wei Chen who is an expert nanotechnologist and Professor Ron Schachar, an ophthalmologistand physicist are studying the potential of applying nanotechnology to the lens.Professor Pierscionek said: “Nanotechnology offers us the prospect of an improved understanding of the intactprotein arrangements and how these may change with cataract formation. This is groundbreaking work because forthe first time it offers the prospect of penetrating the intact lens and tagging the proteins in their natural arrangementsto identify early structural changes that precede cataract formation. This information is vital for the development ofnon surgical methods for reversing the effects of cataracts.”Pioneering Research to Unravel the Secrets of Cancer CellsA trans-Atlantic tie up between scientists at the University of Ulster and the Tufts UniversitySchool of Medicine in Boston could lead to a greater understanding of the triggers that affectcancer cells. The Boston scientists, led by Professors Ana Soto (pictured left) and CarlosSonnenschein, have developed a 3-D model of the mammary gland which allows them tostudy how cells can organize to form tissues and how cancer cells become normal again.This research, allied to the world-leading bio-imaging technology available at the Centre forAdvanced Imaging (CFAI) at UU’s Coleraine campus, could unlock vital secrets about thedevelopment of cancer.Professor Soto, Professor of Anatomy and Cellular Biology at Tufts, is working alongsideUU’s Professor Vyvyan Howard (Professor of Bio-Imaging), Dr George McKerr (Director of the CFAI) and Dr KurtSaetzler (Lecturer in Computational Biology).13

4. BIOMEDICAL GENOMICS RESEARCH GROUPOVERVIEW BY THE GROUP LEADERThe Mission of the Biomedical Genomics Research Group is to conduct research that will lead to a greaterunderstanding of the function of genes and regions for which there is no known function (Functional Genomics);the molecular understanding of gene regulation and gene expression patterns; and, ultimately, the development ofnovel techniques to therapeutically alter the expression of affected genes.The Group has extensive expertise relating to transcriptional regulation, key proteomic- and nucleic acid- basedtechniques (SNP, methylation, microarray, gene knockout, QTOF MS based de novo protein sequencing, MALDI,Yeast-2-hybrid, 2-D PAGE); structural biology (solution NMR spectroscopy); data integration and pathway modelling(Systems Biology). Genomics, proteomics and Systems Biology are strongly inter-related and many complexbiological and biomedical questions demand an integration of these approaches.Therefore, the Group works in contact with most of the research groups within the Biomedical Sciences ResearchInstitute (BMSRI), and particularly with the Systems Biology Research Group.The group is involved in all major aspects of transcriptional regulation ranging from:• the investigation of basic mechanisms of gene regulation;• the investigation of the structural basis for mechanisms of transcriptional control and regulation;• the design of nucleic acid based composites to therapeutically modulate aberrant gene expression patterns;• the analysis of the interplay of disease and a major class of transcriptional regulators (the “superfamily” ofnuclear hormone receptors with a specific focus on the vitamin D receptor);• the analysis of the correlation between genetic variability (SNPs), gene expression, promoter methylationstatus and specific diseases.14

GROUP MEMBERSAcademic Staff:Professor Tony (AJ) Bjourson, Director & Group LeaderProfessor of GenomicsDirector of Biomedical Sciences Research InstituteContact details:T: +44 (0)28 70324885aj.bjourson@ulster.ac.ukIn addition to his role as Director of the Biomedical Sciences Research Institute, Professor Tony Bjourson leadsthe Biomedical Genomics Research Group. Professor Bjourson currently serves as a Director on the boards oftwo companies: the Clinical Translation Research & Innovation Centre (C-TRIC) aimed at translating biomedicalresearch outputs from laboratory bench to patient bedside; and he also serves on the Board of Directors of theUlster venture company UUTECH Limited.Professor Bjourson’s current research is focused on genomics based personalized medicine and his mainresearch interests and expertise are in the areas of: molecular biology and pharmacogenomics. He has activecancer research collaborations with Belfast City Hospital and cancer systems biology collaborations with DanielBerrar (Kitano Lab, Japan) and with clinicians at Altnagelvin Hospital; as well as Rheumatoid arthritis researchcollaborations with Belfast City Hospital and Musgrave Park Hospital.Professor Bjourson is also involved in collaborative research on the genomics & proteomics of snake andamphibian venoms aimed at the isolation of new clinically relevant pharmaceutical drugs.Main research activities have included:• the isolation of biomarkers for personalised medicine relating to degenerative diseases including breast cancer(invasion and metastasis associated biomarkers);• an in vitro model of the pathway leading to breast cancer invasion has been generated and the genomic, transcriptomic(microRNA/mRNA), methylation status & proteomic signatures associated with invasion are investigated using laboratorytechnologies integrated with a systems biology approach;• Rheumatoid arthritis - responsiveness to anti TNF alpha (SNP typing/KIR genotyping anti-TNFα drug responsemicroarray expression analyses) (collaboration with Belfast City Hospital / Musgrave Park Hospital].15

Recent Funding Initiatives:C-TRIC: Academia-Business-Clinical Research Facility–Altnagelvin Hospital Site (partnership between the WesternHealth and Social Care Trust in partnership, the University of Ulster and Derry City Council) - £1.764 M (£1.3 MINI Intereg IIIa Programme; £464,000 ILEX Integrated Development Fund-IDF).INI Proof of Concept Grant), Personalized Medicine in Breast Cancer: Predicting metastases-free survival in lymphnodenegative breast cancer patients £,79,0002008 (HSC R&D Office Cancer RRG Research Cohesion Grant) Role of IFITM1 in Breast Cancer, £5000Students graduated 2008:Natalie Scott (PhD): The Role of MicroRNAs in Breast Cancer Invasion.Seona McErlean (PhD): Genetic profiling of breast cancer.Crispin Madavo (PhD): Isolation and characterisation of VIP from tape-wormsRecent Publications:Thompson AH, Bjourson AJ, Orr DF, Shaw C, McClean S; Amphibian skin secretomics: application of parallelquadrupole time-of-flight mass spectrometry and peptide precursor cDNA cloning to rapidly characterize the skinsecretory peptidome of Phyllomedusa hypochondrialis azurea: discovery of a novel peptide family, the hyposins;Journal of Proteome Research, 6: 3604-3613, 2007Thompson AH, Bjourson AJ, Orr DF, Shaw C, McClean S; A combined mass spectrometric and cDNA sequencingapproach to the isolation and characterization of novel antimicrobial peptides from the skin secretions ofPhyllomedusa hypochondrialis azurea; Peptides, 28: 1331-1343, 2007Membership of External Committees:Member of Bio-Business Northern Ireland. DETI Northern Ireland Academia-Industry Life & Health Sciences PanelGeneLibrary Ireland (Irish BioBank project) Steering Committee Member 2008-present.GeneLibrary Ireland (Irish BioBank project) Work-Package Chair 2008-present.Member Northern Ireland Science Industry Panel-MATRIX – Life and Health Sciences Horizon Panel.–2007-currentCouncil Member of Irish Society for Human Genetics 2006-presentMember of HPSS R&D Clinical Doctorate Review Panel (2004-2008).Dr Paul ThompsonLecturer in Molecular BiologyContact details:T: +44 (0)28 70323246p.thompson@ulster.ac.ukDr Thompson is primarily interested in the biological activities of the nuclear vitamin D receptor (VDR) and themechanisms through which it mediates the wide range of physiological responses to its cognate Vitamin D ligand.The research projects in Dr Thompson’s laboratory are broadly divided into two main areas of focus:Novel biological actions of VDR as a chemoprotective agent in epithelial-derived tissues:Dr Thompson and others have demonstrated that vitamin D can dictate expression of the CYP3A4 gene in coloncarcinoma cells, a pivotal factor for the metabolism and clearance of many potentially harmful xeno and endobioticcompounds. In expanding upon this concept our more recent data reveal that vitamin D can also regulate the levels ofdrug transporter proteins within the apical membrane of enteric cells. Taken in combination, our findings suggest that16

vitamin D can significantly impact upon the detoxification and expulsion of a range of potentially mitogenic moleculesand that vitamin D may be integral to processes such as drug disposition and the appropriate handling of bile acid andsteroid hormone derivatives across the gut. This work was carried out by Declan Doherty, as part of his doctoralstudies, and as part of a collaborative effort with the Department of Pharmacology, University of Liverpool.Dr Thompson and his team have also examined the potential for VDR and vitamin D to induce expression ofmetabolism-related genes within extra-hepatic ‘non-classical’ sites for CYP expression. With the collaboration ofresearchers at Liverpool and Birmingham, our PhD students, Orla Maguire and Catherine Pollock have demonstratedthat VDR-Vitamin D is a significant modulator of CYP3A4 and CYP3A5 expression in prostate cells. This is an on-goingtopic of research in our laboratory that intends to relate how dietary-derived signalling molecules such as vitamin Dmay effect the bioavailability of testosterone and other growth-regulatory androgens within prostate epithelia.Modulators of VDR activity:Critical to our knowledge of how VDR exerts its pleiotropic effects is knowledge of its associations with otherregulatory proteins. Through performing a genetic screen of a prostate cDNA library we have identified a number ofnovel VDR interacting proteins, which we are currently characterizing for their roles within the vitamin D hormonalpathway. The most potentially exciting among these proteins include members of the SENP and PIAS families, whichwe observe to significantly modulate VDR activity upon interaction. We believe that their relative expression levelsmay be pivotal to how certain tumour types become resistant to the growth-regulatory effects of vitamin D.This work is being carried out by two PhD students, Wai-Ping Lee and Catherine Pollock, with collaborative helpfrom researchers at Arizona State University. In continuing this theme of vitamin D resistance in tumours, we arealso working in collaboration with scientists at Cardiff University in assessing novel chemical inhibitors of vitamin Dcatabolism as chemotherapeutic agents targeted towards aggressive forms of prostate cancer. This work is currentlyfunded by Prostate Cancer UK and has been carried out in our laboratory by Dr Joachim Schimdt.Grants awarded:Society for Endocrinology (£9,500 1 year)“NPAS as a novel interactor of the vitamin D receptor-a role for vitamin D in the peripheral circadian clock?”Prostate Research UK (£30,000 1 year)“Characterization and evaluation of novel CYP2A4 inhibitors as anti-proliferative/pro-differentiating agents targetedtowards hormone refractory prostate cancer.”CEC EU Framework Programme VII (£133,793)“BISON: Bisociation Networks for Creative Information Discovery”Werner Dubitzky, Daniel Berrar, Martin Swain, Paul ThompsonStudents graduated:Declan Doherty “The nuclear Vitamin D Receptor as a Medaiotr of Detoxification Pathways in Enteric Cells”Orla Maguire “Novel chemo-protective roles of the Vitamin D Receptor in prostate cells”Presentations:“The Role Of Reversible De-Sumoylation In The Vitamin D Signalling Pathway”; ENDO 2008: Annual meeting of theEndocrine Society, San Francisco, June 2008Markers of esteemExternal examiner for PhD examinationUniversity of Liverpool Department of PharmacologyGrant reviewer for National Science Foundation17

Dr Mateus Webba da SilvaLecturer in Pharmaceutical ChemistryContact Details:T: +44 (0)28 70324009mm.webba-da-silva@ulster.ac.ukMost of cellular DNA exists as a double-helix composed of A:T and G:C base pairings.However, nucleic acids can also adopt other architectures. In particular, G-rich sequencescan fold into four-stranded structures denominated G-quadruplexes. Dr Silva’s generalinterests reside in the application of nucleic acids structural & chemical biology tobiomedical problems. Current areas of interest include (i) understanding the role ofG-quadruplex folds in regulation of gene expression; and (ii) design of nucleic acidarchitectures for biomedical and biotechnological applications.Recently, evidence has emerged suggesting that quadruplex architectures regulate geneexpression. Dr Silva and his team have identified putative quadruplex folding regions in aseries of human genes with crucial regulatory functions, investigated the propensity forquadruplex folding utilizing and developing biochemical, biophysical and molecular biology methods, and identifiedligands that selectively target some of these architectures. In these studies they have developed the means to modulatethe productivity of select genes that affect human conditions and disease states. In particular they established theinnate propensity of G-quadruplex folding of a region containing transcription factor binding sites within the proximalpromoter of fibroblast growth factor 2 (FGF2 also known as bFGF). This gene encodes a protein with roles in broadangiogenic, mitogenic, and neurotrophic activities. It is the most extensively studied growth factor and is involvedin numerous cellular functions in various cell types, including angiogenesis, cell proliferation, cell differentiation,tumorigenesis, tissue remodeling, wound healing, and limb formation. They developed methodology to directly assessformation of a specific topology/structure within the context of the double helical region, established the propensityof a DNA segment of a gene to fold into a G-quadruplex. They have thus demonstrated how propensity of a primarysequence to form an identified quadruplex topology perturbs the equilibrium between the closed double helix andopen single strands. Studies on modulation of gene expression continue on systems in vivo.Dr Silva’s team has also identified a set of ligands that induce and/or stabilize the folding of a G-quadruplex in theproximal promoter of OTX2. The orthodenticle homeobox 2 gene (OTX2) encodes a member of the bicoid subfamilyof homeodomain-containing transcription factors. Recently it has been established that OTX2 overexpressioncan trigger a critical period of neuronal plasticity. Modulating regulation of OTX2 expression is believed to playa role in enhancing mental agility in old age, help treat neurological disorders as diverse as Alzheimer’s, stroke,schizophrenia, and autism. These studies continue towards the development of drugs that can up-regulate or downregulateOTX2 expression.Dr Silva’s team is developing fundamental rules for prediction, design and control self-assembly of DNA G-quadruplextopologies. They have translated some of these rules into computational algorithms that have been used to design abinitio a series of small quadruplex topologies (15-35 nucleotides) with exciting properties: they are extremely resistantto DNAse 1 and S1-nuclease, do not denature in the presence of known denaturants, and do not disassemble evenin boiling aqueous considitions! They are currently being investigated towards some biomedical and biotechnologicalapplications.Publications:Webba da Silva M; Geometric formalism for DNA quadruplex folding; Chem. Eur. J., 13: 9738-9745, 2007Webba da Silva M; NMR methods for studying quadruplex nucleic acids; Methods, 43: 264-277, 200718

Markers of Esteem:International Lecturer Award. Global Center of Excellence series of lectures, Kyoto University, Japan. (March 2008)UK Representative, and Working Group Cordinator (Biochemical & Biorecognition Properties) of European ScienceFoundation COST Action MP0802, “Self-Assembled Guanosine Structures for Molecular Electronic Devices”(06/2008).19

5. BIOIMAGING RESEARCH GROUPResearch StrategyThe group is involved in three main strands of research:i) nanotoxicologyii) tissue development, andiii) instrumentation.Nanotoxicology:The Group has been successful in attracting EU FP6 funding of €320,000, ‘NanoInteract’, for research into nanoparticlepreparation techniques for biological substrates, delivery systems and toxicity measurements at the cellular level.Two full-time RAs are involved in this work. The group has also learned that it has been successful in attracting EUFP7 funding €450,000, ‘NeuroNano’, which will start in the near future and allow the expansion of the nanotoxicolgyactivities.Tissue Development:A process that commences in the embryo but goes on throughout life and includes degenerative processes. Onemain area of interest is the vascularisation of tissues in health and disease states such as wound healing and oculardevelopment. During 2008 an EPSRC grant to investigate the role of angiogenesis in wound healing (£260,000 – UUcomponent)) came to an end (Joint between Nottingham, Brighton and UU) which examined the role of bloodvessel growth over time in the same wound and modelling their growth based on structural and physiologicalparameters. This led to several publications on the longitudinal analysis of wounds using epi-fluorescence and confocalmicroscopy, which is a particular strength of the group. We have also attracted a grant from the BBSRC (£356,000 –UU component) will commence in February 2008 in conjunction with colleagues at Heriot-Watt and the Universityof Dundee. This collaborative project is examining the cellular and molecular determinants of retinal vascular plexusformation and how mathematical modelling can be used to predict the outcome of vascular patterning.. Anothermajor strand of interest concerns neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases, usinganimal models. The new FP7 grant will, when it comes on stream, allow for the integration of the neurodegenerativeand nanotoxicology strands of research. Tissue engineering techniques are being investigated with colleagues inBoston (USA) to develop an in vitro model of breast tissue to study the relationship between tissue dysgenesisand cancer. In all the tissue development projects the use of stereology, for which this group has an internationalreputation for innovation and excellence, is a common factor.Instrumentation:This year has seen the finalisation the Centre for Advanced Imaging centred around the 3 new FEI electronmicroscopes recently installed. This includes a unique cryo-dual beam SEM which facilitates ‘nano-milling’ of frozenbiological tissue with imaging able to resolve 2 nanometres. This will prove invaluable in nanotoxicology research.The group is researching, in collaboration with Unilever Research, a Raman spectroscopy facility which will lead to‘chemical mapping’ at the nanoscale, which is going to be the next big development in bioimaging.Members of the Group:Academic Staff:Professor Vyvyan HowardGroup Leader: Professor of BioimagingContact Details:T: +44 (0)28 70323383v.howard@ulster.ac.ukDuring the year Vyvyan Howard was elected a Fellow of the Collegium Ramazzini, one of the foremost institutions20

addressing environment and health, at a ceremony in Carpi in Italy. Bernado Ramazzini (1633-1717) was the firstoccupational physician, linking environment degradation with health outcomes. Professor Howard, a registeredmedical practitioner himself, was elected on the strength of his contribution to the field of environmental pollutionand ill-health.Professor Howard has continued to serve of the UK Government DEFRA Advisory Committee on Pesticides.During this period he co-authored a paper with Professor Luc Montagnier (Irigaray et al, 2007), who recentlyreceived the Nobel Prize for Medicine.Work has continued on the NanoInteract project, which has recently come out of its mid-term assessment withvery positive comments. The University of Ulster’s contribution to this work in the preparation, characterisation andintracellular fate of nanoparticle preparations is being widely recognised. Professor Howard continues to develop theBioimaging Research Group into a widely recognised centre of international importance in the study of nanomaterialtoxicology.Preparative work is commencing on a study to investigate the impact of low dose endocrine disrupting pesticideexposure of the rat fetus during pregnancy. Structural changes to the architecture of tissues will be measured usingnovel stereological techniques, developed within the Bioimaging Research Group, which will lead to the detectionof ‘minimal change pathology’ – being much more sensitive than the classical pathologist in the detection of change.Publications:Barnes CA, O’Hagan BMG, Howard CV, McKerr G; Verification of cell viability at progressively higher scanning forcesusing a hybrid atomic force and fluorescence microscope.” Journal of Microscopy, 228: 185-189, 2007Ellis KA, Innocent GT, Mihm M, Cripps P, McLean WG, Howard CV and Grove-White D; Dairy cow cleanliness andmilk quality on organic and conventional farms in the UK; Journal of Dairy Science, 89: 1938-1950, 2007Ellis KA, Monteiro A, Innocent GT, Grove-White D, Cripps P, McLean WG, Howard CV, Mihm M; Investigationof the vitamins A and E and beta-carotene content in milk from UK organic and conventional dairyfarms; Journal of Dairy Research, 74: 484-491, 2007Irigaray P, Newby JA, Clapp R, Hardell L, Howard CV, Montagnier L, Epstein S, Belpomme D; Lifestyle-related factorsand environmental agents causing cancer: An overview; Biomedicine & Pharmacotherapy, 61: 640-658, 2007Newby JA, Busby CC, Howard CV and Platt MJ; The cancer incidence temporality index: An index to show thetemporal changes in the age of onset of overall and specific cancer (England and Wales, 1971-1999); Biomedicine andPharmacotherapy, 61: 623-630, 2007Sneddon JC, Ritruechait P, Staats de Yanes G and Howard CV; Seasonal influences on quantitative changes in sweatassociatedanatomy in native and thoroughbred horses; Veterinary Dermatology, 19: 163-173, 2008Professor Ana SotoProfessor of Cancer DevelopmentContact Details:a.soto@ulster.ac.ukEndocrine disruptors:Professor Soto and Professor Howard were funded by the Organix Foundation (Pesticide exposure during fetal life,08-11). This research project will reveal whether commonly used pesticides, at current levels of exposure, cause21

developmental alterations that manifest during adulthood.Professor Soto has been invited to speak about fetal causes of adult disease at several venues as speaker and consultant(international conferences, European Environmental Agency). She has also taught a section of the course directedby Professor Howard entitled: Drug metabolism and Toxicology.Carcinogenesis/Tissue architecture:Dr Hendrik Fuss received training in 3D tissue culture at Professor Soto’s Tufts laboratory and, on his return toColeraine, he was able to apply stereology techniques to the analysis of the epithelial structures present in these 3Dcultures. Unfortunately, Dr Fuss left us in November 2008. The efforts of this research resulted in us being invited tosubmit a proposal for the formation of a study group at The Centre for Mathematical Medicine and Biology (CMMB)at the University of Nottingham, as part of the interdisciplinary/integrative training activities of the Virtual PhysiologicalHuman Network of Excellence funded by the EU Framework Programme VII. Our project entitled “Tissuemorphogenesis: the case for tensegrity as a main determinant” was one of the five chosen for the June 2009 workshops.This training program is of national and international relevance, as it is aimed at advancing the use of mathematicaltools to the understanding of normal physiology and physiopathology.Publications:Maffini MV, Soto AM, Sonnenschein C, Papadopoulos N, Theoharides TC; Lack of c-kit receptor promotes mammarytumors in N-nitrosomethylurea-treated Ws/Ws rats; Cancer Cell Int. 2008, 8:5. [Epub ahead of print] PMID:18445266Krause, S, Maffini, MV, Soto, AM, Sonnenschein C; A novel 3D in vitro culture model to study stromal-epithelial interactionsin the mammary gland; Tissue Eng Part C Methods, 14: 261-271, 2008Vandenberg LN, Maffini MV, Schaeberle CM, Ucci AA, Sonnenschein C, Rubin BS, Soto AM; Perinatal exposure to thexenoestrogen bisphenol-A induces mammary intraductal hyperplasias in adult CD-1 mice; Reprod Toxicol, 26: 210-219,2008Soto AM, Vandenberg LN, Maffini MV and Sonnenschein C; Does breast cancer start in the womb? Basic Clin PharmacolToxicol., 102: 125-133, 2008Soto AM, Maffini MV, Sonnenschein C; Neoplasia as development gone awry: the role of endocrine disruptors; InternationalJournal of Androl. 31:288-93, 2008Sonnenschein C, Soto A; Theories of carcinogenesis: An emerging perspective; Semin Cancer Biol. 18: 372-377, 2008Soto AM, Sonnenschein C, Miquel PA; On physicalism and downward causation in developmental and cancer biology;Acta Biotheoretica, 56: 257-274, 2008Crain DA, Janssen SJ, Edwards TM, Heindel J, Ho SM, Hunt P, Iguchi T, Juul A, McLachlan JA, Schwartz J, Skakkebaek N,Soto AM, Swan S, Walker C, Woodruff TK, Woodruff TJ, Giudice LC, Guillette LJ Jr; Female reproductive disorders: theroles of endocrine-disrupting compounds and developmental timing; Fertil Steril, 90: 911-940, 2008Soto AM, Rubin BS, Sonnenschein C; Interpreting endocrine disruption from an integrative biology perspective; MolCell Endocrinol. (in press)22

Dr George McKerrSenior LecturerContact Details:T: +44 (0)28 70324759g.mckerr@ulster.ac.ukDuring the past year, Dr McKerr has established new external collaborations with other institutions and industrywhich use advanced microscopical techniques available at Coleraine to investigate how cells adhere to nanopatternedsurfaces, the nature and rigidity of nanotubes of differing origin as well as the controlled growth of additionalelements on carbon nanotubes. Ongoing work is using dualbeam cryo-technology to examine the arrangement forcoupling of molecular motors along the axoneme of cilia.Real time measurements are being made of molecular binding attempts between isolated bio-adhesive moleculesand living epithelial cell surfaces. An extension of this work is to look at the disruptive influence of external agentsand it is hoped that this approach will become useful in assessing the effect of new compounds as medically activecompounds.Publications:Barnes CA, O’Hagan BMG, Howard CV, McKerr G; Verification of cell viability at progressively higher scanning forcesusing a hybrid atomic force and fluorescence microscope; Journal of Microscopy, 228: 185-189, 2007Dr Christopher MitchellSenior Lecturer in DNA MetabolismContact Details:T: +44 (0)28 70324089ca.mitchell@ulster.ac.ukThe focus of research is the morphological, cellular and molecular determinants of pattern formation in the vasculature.Dr Mitchell is the Principal Investigator (PI) in a group which consists of 3 PhD students, a Research Associate and 4undergraduate project students. With colleagues in the School of Mathematical Sciences (University of Nottingham)the group is also investigating determinants of wound healing using a model which allows continuous monitoring ofvascular growth following injury (EPSRC funded). Wound healing is particularly important clinically in treatment ofvenous and diabetic ulcers as well as surgical scarring.A PhD student within the group is examining the role that anti-angiogenic proteins play in development of theplacenta and particularly how they impact upon intra-uterine growth restriction, a major cause of neonatal morbidityand mortality. Retinal vasculature has a distinct and regular patterning of vasculature, whose disruption is associatedwith the major causes of blindness in the young (retinopathy of prematurity and persistent hyperplastic primaryvitreous [PHPV]) as well as in adults (diabetic retinopathy). In collaboration with Professor Mark Chaplain (Universityof Dundee) and Dr Steven McDougall (Heriot-Watt University) we are developing mathematical models of vasculargrowth (BBSRC funded) which allow predictions of the outcome of vascular patterning in the retina, which may proveuseful in developing treatment strategies for ocular disease (see picture). In addition to the major causes of blindness,the pathological sequelae of all of the major “killer diseases” in the western world (cancer, atherosclerosis anddiabetes) are characterised by inappropriate vascular growth, making the study of the modulators of normal vasculargrowth a high priority for national funding bodies, such as Research Councils. Members of the group regularly presentresults of their research both locally, nationally and at international conferences.23

Publications:Bigot S, Lucas L, Morrow P, Mitchell CA, Saetzler K; Estimating Leukocyte Velocities from High-speed 1d Line ScansOriented Orthogonal to Blood Flow; ISBI 2007: 376-379, 2007Rutland CS, Mitchell CA, Nasir M, Konerding MA, Drexler HCA; Microphthalmia, persistent hyperplastic hyaloidvasculature and lens anomalies following over-expression of VEGF-A 188from the aA-crystallin promoter; MolecularVision, 13: 47-56, 2007Lucas LAG, S Pop SR, Machado MJC, Ma YL, Waters SL, Richardson G, Saetzler K, Jensen OE and Mitchell CA;Experimental and theoretical modelling of blind-ended vessels within a developing angiogenic plexus; MicrovascularResearch, 76: 161-168, 2008Lee PD, Atwood RC, Rockett P, Konerdingn MA, Jones JR, Mitchell CA; Proceedings of SPIE, Vol. 7078, 70780E, 2008[DOI:10.1117/12.795558]Research Staff:Dr Barry O’HaganResearch FellowContact Details:T: +44 (0)28 70324765bmg.ohagan@ulster.ac.ukDr O’Hagan’s main research interests and activities involve the use and development of advanced imaging systemsfor use in a variety of biological research projects.He is responsible for the routine maintenance, alignment and operation of the FEI Centre for Advanced Imaging(electron optics including transmission electron microscopy, Environmental scanning electron microscopy, Cryofocused ion beam microscopy). He liaises closely with FEI field engineers and customer support in fault diagnosisand repair. Development and optimisation of cryo dual beam microscopy for biological samples is the main thrust ofhis work and is ongoing. This includes developing protocols for sample preparation and imaging parameters for bothambient and cryogenic conditions, and have working ‘recipes’ for chemically fixed and unfixed cellular monolayers,resin embedded material and cryo-fractured samples.24

He has trained a large number of other users in the use of optical and electron microscopy to the point where theyare capable of using the instrumentation unsupervised or with minimal supervision.Dr O’Hagan’s first doctoral research student has recently finished her program of work and is awaiting a viva vocein the near future.Project collaborations:In addition to the ongoing development of biological cryo dual beam microscopy, Dr O’Hagan has been closelyinvolved in a number of other research projects within Ulster University, as well as collaborations with externalcompanies and institutions. These include the following:• Transmission electron microscopy of Nanotube structure (NI Bioengineering Centre - NIBEC).• Cryo-Dualbeam microscopy of osteoblast response to nanogrooved substrates. (University Nijmegen MedicalCentre, joint publication pending).• FIB nano-machining of AFM probe tips (Yael Dror, Oxford).• Cryo FIB, variable pressure ESEM Mitochondrial imaging. (University of Leicester, joint publication pending).• Temperature variation in SEM chamber during cryo operation (NIBEC).• TEM polymer structure and formation (Chemistry at Queens University).• Assistance with Nanotoxicology research (NanoInteract).• Assistance with fat emulsion research (CAST award with Unilever Research, Vlaardigan).• Assistance with investigations into bacterial adhesion to cells (CAST award with Unilever Research, PortSunlight).• Preliminary imaging of oil bearing rock core samples. (collaboration with Corex).Fig. 1Cryo Dual beam cross section through malariainfected bloodFig. 2Deconvolved multi-fluorescence image ofmammalian cell25

Publications:Barnes CA, O’Hagan BMG, Howard CV, McKerr G; Verification of cell viability at progressively higher scanning forcesusing a hybrid atomic force and fluorescence microscope; Journal of Microscopy, 228: 185-189, November 2007Edwin Lamers, X Frank Walboomers, Maciej Domanski, Joost te Riet 3 , George McKerr, Barry M O’Hagan, CliffordA Barnes, Lloyd Peto, Falco CMJM van Delft, Regina Luttge, Louis Winnubst, Han JGE Gardeniers and John A Jansen;Nanogrooved substrates influence osteoblast-like cell behavior and extracellular matrix deposition; (submitted toNano Letters)Dr O’Hagan and his colleagues are currently preparing manuscripts detailing sample preparation and imagingparameters for biological dual beam microscopy, and comparative electron imaging techniques. In addition, a numberof joint publications resulting from our collaborations are expected in the near future.Dr Clifford BarnesResearch AssistantContact Details:T: +44 (0)28 70323028c.barnes@ulster.ac.ukDuring the period 1 st August 2007 to 31 st July 2008, Clifford was employed as a post- doctoral Research Assistanton a 3 year contract in the NanoInteract Project, headed by Professor Howard and Dr George McKerr.This work involved testing the potential genotoxicity of amorphous silica nanoparticles through the use of theComet Assay. The results obtained during this period directly challenged a widely cited abstract, which had declaredthat amorphous silica was genotoxic. A close collaboration with the Nofer Institute of Occupational Medicinein Poland was established to ensure results were repeatable across laboratories. A draft paper was presented inPoland at a NanoInteract group meeting. This paper was subsequently submitted for publication in Nano Letters.Clifford’s main research interests involve imaging the uptake of nanoparticles in cultured cells using a range ofhigh-resolution techniques such as Fluorescence and Confocal Microscopy, Environmental, Transmission and HighVacuum Scanning Electron Microscopy and Cryo-Dual Beam Scanning Electron Microscopy. These techniques, inconjunction with stereology, will be used to quantify nanoparticle uptake in a study, which will take place inpartnership with University College Dublin.Environmental Scanning Electron imagesFig 3. - Secondary electron image taken in ESEM. Filopodia (labelled F) andlamellipodia (labelled L) are visible. A piece of debris (labelled D) is indicatedFig 4. - ESEM backscattered image. Ceria nanoparticles are visible asbright spots. Nucleoli (labelled N) and debris (labelled D) are visible.26

Clifford is responsible for the routine maintenance, alignment and operation of the FEI Centre for Advanced Imaging(electron optics including transmission electron microscopy, Environmental scanning electron microscopy, Cryofocused ion beam microscopy). He liaises closely with FEI field engineers and customer support in fault diagnosisand repair. Development and optimization of cryo dual beam microscopy for biological samples is the main thrust ofhis work and is ongoing. This includes developing protocols for sample preparation and imaging parameters for bothambient and cryogenic conditions, and have working ‘recipes’ for chemically fixed and unfixed cellular monolayers,resin embedded material and cryo-fractured samples.He has trained a number of other users in the use of our electron microscopes to the point where they are capableof using the instrumentation unsupervised. or with minimal supervision.In addition to the ongoing development of biological cryo dual beam microscopy, Clifford is also closely involvedin a number of other research projects and collaborations with external companies and institutions. These includethe following:• Transmission electron microscopy of Nanotube structure (NIBEC).• Cryo-Dualbeam microscopy of osteoblast response to nanogrooved substrates. (University Nijmegen MedicalCentre, joint publication pending).• FIB nano-machining of AFM probe tips (Yael Dror, Oxford).• Cryo FIB, variable pressure ESEM Mitochondrial imaging. (University of Leicester, joint publication pending).• Temperature variation in SEM chamber during cryo operation (NIBEC).• TEM polymer structure and formation (Chemistry at Queens University).• Assistance with Nanotoxicology research (NanoInteract).• Assistance with fat emulsion research (CAST award with Unilever Research, Vlaardigan).• Assistance with investigations into bacterial adhesion to cells (CAST award with Unilever Research, Port Sunlight).• Preliminary imaging of oil bearing rock core samples. (collaboration with Corex).Publications:Barnes CA, O’Hagan BMG, Howard CV, McKerr G; Verification of cell viability at progressively higher scanning forcesusing a hybrid atomic force and fluorescence microscope; Journal of Microscopy, 228: 185-189, November 2007Mr Andreas ElsaesserResearch AssistantContact Details:T: +44 (0)28 70324765a.elsaesser@ulster.ac.ukAndreas Elsaesser studied physics at the Technical University, Munich and the University of Liverpool, United Kingdom.He graduated in 2006 with a Dipl.Phys. (corr. M.Sc.) in Surface and Interface Physics, Nuclear Physics and Astrophysicsand finished his studies investigating Complex Plasmas with ultra-fast Laser-Tomography.Andreas is currently employed as a research assistant in the BioImaging Research Group working for NanoInteract,a FP6 project investigating interaction mechanisms between nanoparticles and biological systems.Research Interests:Interaction of Nanoparticles and biological systemsIn order to understand the principle interaction mechanisms of nanoparticles and living cells, we measure nanoparticleuptake ratios and pathways of nanoparticles in cells using Transmission electron microscopy and Scanning electronmicroscopy.27

We also measure the genotoxic effects of nanoparticles using the comet assay in relation to size and atomiccomposition.(a) Hela cells and 250nm silica nanoparticles, (b) ceria (CeO 2) nanoparticles taken up by a (c) plain ceria nanoparticles3T3 fibroblast cell,Part of this work was presented at the Annual Meeting of NanoInteract (Development of a platform and toolkit forunderstanding interactions between nanoparticles and the living world) in Lodz, Poland, 14 th /15 th of March 2008.Nanoparticles and electromagnetic RadiationElectromagnetic radiation and matter interact predominantly by three different mechanisms: Comptonscattering, photoelectric effect and pair production. We are interested in photoelectrons produced bynanoparticles and their impact on biological systems. Monte-Carlo Simulations show a 25,000 fold increaseof secondary electrons of a 2nm gold particle compared to the mass-equivalent 2cm particle.Secondary electron production by 10 keV primary photons within the target and escaping electrons overlayed by the target geometry for water(a), gold (b) and uranium (c). Figure (d)-(f) shows the corresponding energy deposition.Preliminary results were presented on the ESF-EMBO Symposium, 3 rd -8 th November 2007, Spain (Probing Interactionsbetween Nanoparticles/Biomaterials and Biological Systems – Alternative Approaches to Bio- and Nano-safety) and onthe Second Meeting of NanoInteract (Development of a platform and toolkit for understanding interactions betweennanoparticles and the living world), 9 th November 2007, Spain.Publications:Barnes CA, Elsaesser A, Arkusz J, Smok A, Palus J, Lesniak A, Salvati A, Hanrahan JP, Jong WH, Dziubaltowska E, StepnikM, Rydzynski K, McKerr G, Lynch I, Dawson KA and Howard CV; Reproducible Comet Assay of Amorphous SilicaNanoparticles Detects No Genotoxicity, Nano Lett , 8: 3069-3074, 2008Samsonov D, Elsaesser A, Edwards A, Thomas HM, Morfill GE; High speed laser tomography system; Review of ScientificInstruments, 79: 35102, Mar 200828

INDICATORS OF ESTEEMMembership of External Committees/Professional Bodies (Howard):• President: International Society of Doctors for the Environment 2007-2008• Elected Fellow of the Collegium Ramazzini, Carpi, Italy• Honorary Life Fellow: International Society for Stereology• Fellow of the Royal College of Pathologists• Member British Society of Toxicological Pathologists• Member: European Teratology Society• Member of DEFRA ACP (Advisory Committee on Pesticides) 2003-2008• Member of the Medical and Toxicology Panel of the ACP• Member DETI Advanced Materials Panel• Member Northern Ireland Tumour Bank Working Group• Editorial board, Journal of Microscopy• International Editorial Advisory Board, Forma• Editorial board, Electronic Journal of Pathology and HistologyInvitations to speak (Howard)5 th October 2007 – Invited speaker FEI debate on ‘Nanotechnology in food production’5 th -9 th November 2007 – Invited speaker European Science Foundation/EMBO conference on nantotoxicology StFeliu, Spain.30 th November 2007 – Invited to address the Council of Europe, Paris on “Chemical Risk Assessment – an antidoteto precaution?”Seminars/conferences (Soto)2007 Speaker at the colloquium: Endocrine disruptors and human health”. Argentinean association of Physicians forthe environment, August 15.2007 Discussant, Symposium on Health and Disease at The Intersection of Biology, Environment and Society, Universityof Coimbra, Portugal, October 22-23.2008 Speaker at the European Environmental Agency Symposium on “Multi-Causality and Complexity: Implicationfor Evaluating Evidence and Precautionary Prevention”, January 21-22.2008 Seminar Speaker “Does breast cancer start in the womb?” Graduate Program in Endocrinology at RutgersUniversity, Brunswick, NJ, April 4.2008 Seminar Speaker “Does breast cancer starts in the womb?” Graduate Program in Biology, Boston University,Boston, MA, April 7.2008 Speaker at the course “Communicating Complexity in Science”. Course Director: Louis Guillette. Universityof Florida at Gainesville, April 8.2008 Speaker, Gordon Research Conference on Mammary Gland Biology, Il Ciocco, Italy,June 1-62008 Special Speaker at the Dinner Panel, Gordon Research Conference on Environmental Endocrine Disruptors,Waterville Valley Resort, New Hampshire, June 8-1329

6. CANCER AND AGEING RESEARCH GROUPRESEARCH STRATEGYCancer is most commonly a disease of old age, brought on by cumulative mutagenic responses to DNA damage;probably, some of the factors producing ageing are similar. This Group has, therefore, investigated factors affecting themutability and growth controls of human cells and of a variety of animal models. Cancer-related work encompassesa range of topics relevant to therapy, diagnosis or causation. Direct research into ageing involves studies of ageingsyndromes: such as Alzheimer’s Disease and Werner Syndrome.The Group uses a wide range of facilities, including proteomic facilities with 2D electrophoresis and a spot-pickingrobot, a QTOF Ultima mass spectrometer, Xray and caesium gamma sources, whole-body imaging for mice, andventilated isolation cages for handling immuno-compromised mice.MEMBERS OF THE GROUPAcademic Staff:Professor Stephen Downes, Group LeaderProfessor of Cancer BiologyContact Details:T: +44 (0)28 70324121cs.downes@ulster.ac.ukProfessor Downes’ main research interests are:in cancer biology:• Cell cycle control, concentrating on control of progression into G2/M by decatenation, damage and replicationcheckpoints;• DNA damage as detected by the Comet assay, and variations of that assay;• Creation of novel vectors to display results of different classes of DNA damage;• DNA repair mechanisms (excision, postreplication, mismatch); and molecular basis of repair deficiency inthymidine kinase defective cells;• Signaling networks, particularly in lung and colon cancer;• Nutritional aspects of carcinogenesis, particularly mechanisms by which dietary folate or salicylate insufficiencymay affect colon cancer.in ageing:• Mechanisms defective in progeroid syndromes, especially Werner syndrome and Cockayne syndrome;• Excess DNA damage in Alzheimer syndrome.30

Research deliverables:Better understanding of mechanisms of carcinogenesis and of ageing, leading to rationally based strategies for avoiding,delaying or treating them.Better understanding of the rather tenuous relationship between nationality and ethnic origins.Professor Downes was a Member of the 2008 RAE Sub-Panel 12, Allied Health Professions and Studies and an invitedspeaker on: “Systems Biology for Medical Applications”, FW6 Workshop on Cancer-Ageing link, Paris, in February2008.Publications:Fuss H, Kurth MJ, Downes CS, Dubitzky W; Deactivation of Src family kinases: Hypothesis testing using a Monte Carlosensitivity analysis of systems-level properties, Journal of Computational Biology, 14: 1185-1200, 2007Graham JE, Moore JE, Jiru X, Moore JE, Goodall EA, Dooley JS, Hayes VE, Dartt DA, Downes CS, Moore TC; Ocularpathogen or commensal: a PCR-based study of surface bacterial flora in normal and dry eyes; Investigative OphthalmolVis Sci., 48: 5616-23, 2007Sanderson P, Stone E, Kim YI, Mathers JC, Kampman E, Downes CS, Muir KR and Baron JA; Folate and colo-rectalcancer risk; British Journal of Nutrition, 98: 1299-304, 2007Tömöry G, Csányi B, Bogácsi-Szabó E, Kalmár T, Czibula Á, Csõsz A, Priskin K, Mende B, Langó P, Downes CS and RaskóI; Comparison of maternal lineages and phylogenetic analysis of ancient and modern Hungarian populations; AmericanJournal of Phys. Anthropol., 134, 354-368, 2007Csányi B, Bogácsi-Szabó E, Tömöry G, Czibula Á, Priskin K, Csõsz A, Mende B, Langó P, Csete K, Zsolnai A, ConantEK, Downes CS and Raskó I; Y-chromosome analysis of ancient Hungarian and two modern Hungarian-speakingpopulations from the Carpathian Basin; Ann Human Genetics, 72: 519-534, 2008Fuss H, Dubitzky W, Downes CS and Kurth MJ; Src family kinases and receptors: analysis of three activation mechanismsby dynamic systems modeling; Biophysical Journal, 94: 1995-2006, 2008Graham JE, Graham RLJ, Beirne R, McGilligan VE, Downes CS, Moore JE, Moore CBT, McMullan G; The use ofconjunctival swab for the proteomic characterisation of Dry Eye Syndrome; Journal of Proteomics and Bioinformatics;1: 20-33, 2008Wasson GR, Downes CS and McKelvey-Martin VJ; The use of the Comet assay in the study of human nutrition andcancer; Mutagenesis, 23: 153-162, 2008Professor Stephanie McKeownProfessor of Cancer Biology31

Professor Anthony P McHaleProfessor of Medical BiotechnologyContact Details:T: +44 (0)28 70324616ap.mchale@ulster.ac.ukIn addition to ongoing interests in the therapeutic application of electric and ultrasonic fields in the treatment ofcancer, Professor McHale’s recent work has expanded specifically upon the application of modified ultrasonic fieldsin areas such as site-specific delivery of active cancer chemotherapeutic agents and in site-specific delivery of genesfor applications in gene therapy approaches to the treatment of cancer.Recently active research collaboration has been established with the Ludwig Boltzmann Institute for Experimentaland Clinical Traumatology in Vienna where Professor McHale delivered a guest lecture on ‘Cell membrane poration:Selected Applications’. In addition to the above areas of research Prof. McHale also serves as a member of theEditorial Board for Biotechnology Letters and has served as a reviewer for a wide range of scientific journalsincluding Cancer Letters, Journal of Pharmacy and Pharmacology, Ultrasound in Medicine and Biology and theJournal of Orthopaedic Research.During this time, Professor McHale also received a short-term grant from Gendel Limited to work on ‘The interactionof ultrasound with human skull bone’ .Publications:Li YS, Reid CN, McHale AP; Enhancing ultrasound-mediated cell membrane permeabilisation (sonoporation) using ahigh frequency pulse regime and implications for ultrasound-aided cancer chemotherapy; Cancer Letters, 266: 256-262,2008European Patent Granted:Ablation device: EP 1506039 McHale AP & Russell, LJ (2008)Professor Valerie McKelvey-MartinProfessor of Molecular BiosciencesDeputy-Head, Department of Pharmacy & Pharmaceutical SciencesContact Details:T: +44 (0)28 70324771v.mckelvey@ulster.ac.ukProfessor McKelvey-Martin has a research interest in the area of DNA damage and repair, particularly in the role ofThymidine kinase in these processes. Using comet technology and in particular Comet Fish technology, new insightsinto this role have been discovered and are being further investigated using other molecular techniques. ProfessorMcKelvey-Martin also has an interest in the mechanism by which aspirin is involved in cancer prevention, and indeedin the public health debate on the use of prophylactic aspirin. Her research interests also include developing effectiveways to engage the public in science, particularly in scientific issues which have implications for health and wellbeing.In May 2008, Valerie was appointed as a Member of an Expert Committee to advise a government-commissionedproject on “Emerging Technologies and Health” with regard to policy. She is also a Member of the Department ofEducation and Learning (Northern Ireland) Working Group on ‘Science, Technology, Engineering and Mathematics (STEM)”;32

and was the Guest Editor for a special issue of Mutagenesis on “The Comet Assay” (Vol. 23(3), OxfordUniversity Press, May 2008).Professor McKelvey-Martin was awarded a joint grant (£5,000) from the Wellcome Trust to co- host “A TransatlanticDialogue on Emerging Technologies: Bioethics Symposium” with Professor Nigel M de S Cameron from the Centre forPolicy on Emerging Technologies, Washington, USA for policy makers. The Symposium was held in London in January2008 and is a launching pad for further discussion and networking.Professor McKelvey-Martin have continued to work on three-year Wellcome Trust funded project entitled “ForwardThinking Northern Ireland”. This project aims to give young adults the skills and knowledge needed for aneffective engagement with science and the possible consequences that science has for our Society. Schools involvedreceive 8 sessions that focus on exploring questions relating to contemporary science issues. Topics explored includecloning pets, enhancing humans, intensive farming practices, pre-implantation genetic screening and alternative diets.The discussions are led by a facilitator (Research Associate) and use the community of enquiry method to supportstudents in asking and investigating their own questions. The sessions give students the opportunity to think critically,discuss and make decisions about the social and ethical implications of scientific advances. The effectiveness of thisapproach is being evaluated, as part of a doctoral thesis, by Research Associate and PhD student, Ms Lynda Dunlop.The Forward Thinking project serves to fulfil several of the curriculum requirements for Local and Global Citizenshipand Science and will offer the added opportunity for small self-selecting teams to work together to produce awinning entry on an aspect of science policy related to the topics discussed in the sessions.During the year under review, Professor McKelvey-Martin continued to manage £75,000 sponsorship grant fromthe Bank of Ireland, to fund a series of lectures for the promotion of Science in Society; as well as a £22,500 grantfrom The Honourable The Irish Society to fund 3 placement bursaries during the year.Publications:McKenna DJ, McKeown SR and McKelvey-Martin VJ; Potential use of the comet assay in the clinical management ofcancer; Mutagenesis, 23(3): 183-190, 2008(doi: 10.1093/mutage/gem 054)Wasson GR, McKelvey-Martin VJ and Downes CS; The use of the comet assay in the study of human nutrition andcancer; Mutagenesis, 23(3): 153-162, 2008(doi: 10.1093/mutage/gen 003)McKelvey-Martin VJ and McKenna DJ; Developments and Applications of the comet-FISH assay for the study of DNAdamage and repair, in The Comet Assay in Toxicology; (Eds Dr Alok Dhawan & Professor Diana Anderson); The RoyalSociety of Chemistry, London (in press)33

Professor Stephanie McKeownProfessor of Cancer BiologyContact Details:T: +44 (0)28 70323542sr.mckeown@ulster.ac.ukProfessor McKeown’s main area of interest is tumour biology with particular reference to hypoxia and bioreductivedrugs, and their combination with radiotherapy and chemotherapy.Tumour hypoxia is a critical feature of many solid tumours and is known to reduce the efficacy of both radiotherapyand chemotherapy. Bioreductive drugs are designed to specifically target hypoxic cells and can be used to treat solidtumours to enhance the effects of standard therapies. This class of cytotoxic agent is particularly useful as it is designedto be administered as a non-toxic prodrug. It becomes cytotoxic in hypoxic cells and therefore causes limitedsystemic toxicity since the cytotoxic species is only produced in areas of hypoxia i.e. primarily in tumours. In collaborationwith Professor LH Patterson (Director, Institute of Cancer Therapeutics, University of Bradford) our work hasdemonstrated that AQ4N (Banoxantrone) is the best bioreductive drug available. Pre-clinical studies carried out atthe University of Ulster have provided convincing evidence of the efficacy of AQ4N and further supporting evidencehas come from several other groups world-wide. Clinical trials of AQ4N combined with radiotherapy and chemotherapyare ongoing in both the UK and USA (reviewed in an invited paper indicated below).This year we have identified novel responses to the treatment of tumours which indicate that we need to moreclearly understand what occurs in the initial days after treatment with a number of drugs. There are several consequencesof these studies which are currently not clearly recognised in the scientific community. We plan to use ourknowledge to develop new ‘informed schedules’ and test them for efficacy. In addition we plan to follow the biological/ molecular consequences of these changes. A greater understanding of these changes could lead to the design ofmore effective ways to eradicate solid tumours.Professor McKeown is currently the University of Ulster’s Designated Individual (DI) as described under the HumanTissue Act (2004). In this capacity she oversees all of the activities relating to storage and use of human tissues usedprimarily for research within the University and its associated sites. She is also the Chairperson of the Irish RadiationResearch Society (and co-organiser of its scientific meeting in Dublin, October 2007) and a member of: the BritishInstitute of Radiology (and its Cancer and Radiation Biology Committee); the National Cancer Research Institute,UK (and its Radiotherapy Trials Clinical Studies Group); the Council of the International Association for RadiationResearch; the Ireland-Northern-Ireland-NCI-USA Cancer Consortium (and the Scientific Committee for its biennialmeeting in Dublin, 2008).Professor McKeown has been the Chairperson of the Northern Ireland (NI) Cancer Recognised Research Groupsince 2007 as well as being the Treasurer to the NI Committee of the Institute of Biology since 2004. She has alsoacted as Radiobiology specialist examiner, for the Clinical Oncology examinations at the Royal College of Radiologistsin London and became an External Assessor for the University of Malaya, Kuala Lumpar in 2008.Publications:Butterworth KT, McCarthy HO, Devlin A, Ming L, Robson T, McKeown SR, Worthington J; Hypoxia selects for androgenindependent LNCaP cells with a more malignant genotype and phenotype; International Journal of Cancer, 123: 760-768, 2008O’Keeffe MB, Devlin AH, Burns AJ, Gardiner TA, Logan ID, Hirst DG, McKeown SR; Investigation of pericytes, hypoxiaand vascularity in bladder tumours: association with clinical outcomes; Oncology Research, 17: 93-101, 2008O’Rourke M, Ward C, McKenna J, Worthington J, Valentine A, Hirst DG, McKeown SR; Evaluation of the anti-angiogenicpotential of AQ4N; Clinical Cancer Research, 14: 1502-1509, 200834

Devlin AH, McIlroy M, McKeen HD, Bonde P, Menezes AAC, Bell Z, Swarbrick CJ, Robson T, DG Hirst, Campbell FC,McGuigan JA, McKeown SR; Cytochrome P450 1B1 expression in rat oesophageal tumorigenesis promoted by gastricand duodenal reflux; Molecular Carcinogenesis [Jul 10, Epub ahead of print] 2008Invited peer reviews:McKeown SR, Cowen RL, Williams KJ; Bioreductive Drugs: from Concept to Clinic; Clinical Oncology, (Royal Collegeof Radiologists), 19: 427-442, 2007McKenna DJ, McKeown SR, McKelvey-Martin VJ; Potential use of the comet assay in the clinical management of cancer;Mutagenesis, 23(3): 183-190, 2008Dr Christian HölscherSenior Lecturer in NeurobiologyContact Details:T: +44 (0)28 70324178christian_holscher@mac.comDr Hölscher’s main research interest is in Alzheimer's Disease. Alzheimer’s is a neurodegenerative disease that increasinglyaffects the population of industrialized countries. One of its hallmarks is the appearance of amyloid proteinaggregates in the brain. Currently, the cellular mechanisms of Neurodegeneration induced by different amyloid fragmentsare under intense investigation. Using the techniques of in vivo recording of neuronal activity, a battery of differentlearning tasks, and histological analysis, the short- and long-term effects of amyloid peptides (the peptide thataggregates in the brains of Alzheimer patients) are analysed. One project focuses on the analysis of transgenic animalsthat over-express the human form of amyloid precursor proteins.The neurodegenerative effects of amyloid fragments activate a cascade of biochemical processes that eventually leadto cell death. Key processes in this cascade include the increased calcium influx into neurons via ion channels, theactivation of enzymes that produce free radicals, and the induction of auto-inflammatory responses.Several strategies to identify and block these processes are in progress. Collaborations with the Univeristy’s DiabetesResearch Group to develop novel neuroprotective peptides are underway. They have developed novel proteaseresistantinsulin-like incretin analogues intended to treat patients with Type 2 Diabetes, but that also have growthfactor-like properties in the brain and are very promising in preventing neurodegeneration induced by amyloid fragments.A number of novel incretin analogues have been tested in different mouse models of Alzheimer’s disease andhave shown very promising effects.During the period under review, Dr Hölscher continued to manage a pilot project grant (£17,000) from the AlzheimerResearch Trust for the “Analysis of novel GLP-1 agonists on neuronal survival”; as well as continuing to manage35

an Alzheimer Research Trust collaboration grant (£30,000) to investigate “Insulin receptor activity in the brains of amouse model of Alzheimer’s Disease”. He has, more recently, obtained a significant project grant (£148,000) from theAlzheimer Society to conduct an “Analysis of novel GLP-1 agonists on neurodegenerative processes in a mouse model ofAlzheimer’s Disease”.Deliverables:The research focuses on novel therapies for the treatment of Alzheimer’s Disease. Median term deliverables are theidentification and development of novel protease-resistant incretin analogues that can be applied safely and that activateneuroprotective and regenerative mechanisms in neurons. Ideally, novel treatments that prevent and protectfrom neurodegenerative processes will be developed, which would be of major benefit to the affected part of thepopulation.Dr Hölscher is a member of the Editorial Board of the journal ‘Artificial Intelligence’ and was recently appointed atthe Co-ordinator of the Alzheimer Research Trust Network in Northern Ireland (the official launch of which tookplace in Belfast in February 2008).The Official Launch of theAlzheimer Research Trust Network of Northern Irelandat Belfast castle, 19 th February 2008From LtoR: Lady Sylvia Hermon MP, Dr Janet Johnston (QUB representative),Marie Janson (Head of the ART research section) and Dr Christian Hölscher (UU representative)Dr Hölscher was also invited to speak at the Annual Meeting of the Society for Neuroscience (San Diego, USA) inJuly 2008.Publications:Gengler S, Gault VA, Harriott P, Hölscher C; Beta-amyloid (25-35) induced impairments of hippocampal synaptic plasticityare dependent on stimulation-protocol, genetic background, and aggregation state; Experimental Brain Research,179: 621-630, 2007Holscher C, Gengler S, Gault VA, Harriott P, Mallot HA; Soluble beta-amyloid[25-35] reversibly impairs hippocampalsynaptic plasticity and spatial learning; European Journal of Pharmacology, 561: 85-90, 2007Gault VA and Hölscher C; A novel GIP agonist facilitates hippocampal LTP and reverses the impairment of LTP inducedby beta-amyloid; Journal of Neurophysiology, 99: 1590-1595, 2008Gault VA and Hölscher C; GLP-1 agonists facilitate hippocampal LTP and reverse the impairment of LTP induced bybeta-amyloid; European Journal of Pharmacology, 587: 112-117, 2008Invited Reviews:Li L and Hölscher C; Common pathological processes in Alzheimer Disease and Type 2 Diabetes: a review; BrainResearch Reviews, 23: 58-65, 2007Hölscher C and Li L (2008): New roles for insulin-like hormones in neuronal signalling and protection: new hopes fornovel treatments of Alzheimer’s Disease? Neurobiol Ageing (in press).Book:‘Mechanisms of information processing in the Brain: Information Processing by Neuronal Populations’. C Holscherand M Munk (Eds.). Cambridge University Press, Cambridge UK. 2008, ISBN 978-0-521-87303-136

Book Chapters:Hölscher C (2008) Functional roles of Theta and Gamma oscillations in the association and dissociation of neuronalnetworks in primates and rodents. Chapter 7, in: Information Processing by Neuronal Populations, Hölscher and Mink(Eds)., Cambridge University Press, ISBN 978-0-521-87303-1Hölscher C (2008) How could populations of neurons encode information?. Chapter 1, in: Information Processing byNeuronal Populations, Hölscher and Mink (Eds)., Cambridge University Press, ISBN 978-0-521-87303-1Dr Jenny WorthingtonLecturer in Biomedical SciencesContact Details:T: +44 (0)28 70323541j.worthington@ulster.ac.ukDr Worthington’s main research interests include:Tumour microenvironment:Our recent research in this area has utilised the dorsal skin flap model to observe blood vessel patterning in tumoursafter treatment with chemotherapy agents. We aim to exploit these changes to develop new treatment regimensfor cancer therapy.Gene Therapy:With our collaborators in Queens University, Belfast, we have used transcriptional regulation and novel deliveryvector design to optimise delivery of iNOS to solid tumours. This protein produces nitric oxide which is extremelytoxic to tumour cells.Apoptosis:A new research project, involving Gillian Browne (PhD student) has identified a new transcription factor which isimportant in controlling apoptosis in breast and prostate cancer. We aim to develop this project further, examininghow high levels of this protein can affect the response of tumour cells to various cancer therapies.Publications:Adams C, McCarthy H, Coulter J, Worthington J, Murphy C, Robson T, Hirst DG;Nitric oxide synthase gene therapyenhances the toxicity of cisplatin in cancer cells; Journal of Gene Med e-pub. (2008)Butterworth KT, McCarthy HO, Devlin A, Ming L, Robson T, McKeown SR, Worthington J; Hypoxia selects for invasive,androgen independent and apoptosis-resistant LNCaP cells; International Journal of Cancer, 123: 760-768, 2008Coulter J, McCarthy HO, Worthington J, Robson T, Scott SD, Hirst DG; Enhancement of the synthetic CArGpromoter by radiation and hypoxia; Gene Therapy, 15: 495-503, 2008Marginol L, Robson T, McCarthy HO, Worthington J, Murray M, Hollywood D, Lawler M, Hirst DG; The tissueplasminogen activator gene promoter: a novel tool for radiogenic gene therapy? Journal of Gene Med, 10: 1032-1038, 2008O’Rourke M, Ward C, Worthington J, McKenna J, Valentine A,Robson T, Hirst DG, McKeown SR; Evaluation ofthe anti-angiogenic potential of AQ4N; Clinical Cancer Research, 14: 1502-1509, 2008Wilson C, Scullin P, Worthington J, Seaton A, Maxwell P, O’Rourke D, Johnston PG, McKeown SR, Wilson RH, O’Sullivan37

JM, Waugh DJJ; Dexamethasone potentiates the anti-angiogenic activity of docetaxel in castration-resistant prostatecancer; British Journal of Cancer, 99: 2054-2064, 2008Research Staff:Dr Raellene DareResearch AssociateDr Dare’s main areas of interest are:• effect of folic acid supplementation in colon cancer• use of microarrays to determine methylation differences in response to changes in folate• use of microarrays for investigating differences in gene expressionDiminished folate status has been implicated in the development of cancers, with colorectal cancer being a compellingexample. The role of folate in the development of colorectal cancer is not clear-cut, however it is known that folatehas a role to play in the methylation of DNA molecules. A diet deficient in folate can lead to the hypomethylationof genes, which in turn may lead to inappropriate gene expression and carcinogenesis. We are currently usingmicroarray technology as a high throughput method for studying the methylation status of multiple genes forindividuals with colorectal tumours who have undergone dietary folate supplementation. We have also used ourmethylation microarray method in order to study the effect of folate on the SW620 colonic cell line.We also wish to investigate the correlation between gene expression changes and methylation differences due tofolate supplementation. We hope to be able to find a number of novel biomarkers which should indicate thoseindividuals more likely to be at risk from colorectal cancer.Methylation MicroarrayDr Andrea DevlinResearch AssociateContact Details:T: +44 (0)28 70323545ah.devlin@ulster.ac.ukThe main focus of Dr Devlin’s research during this period investigated the factors controlling expression of CYP1B1,member of the cytochrome P450 family. The enzyme is thought to play a role in development of cancer as it canactivate carcinogens and is expressed at high levels in human tumours. Using molecular biology techniquesshe has demonstrated that CYP1B1 protein levels are regulated by a novel post-transcriptional mechanism and these38

esults are in preparation for submission to a peer-reviewed journal. During this period she also contributed tothree other peer-reviewed journal articles and has been involved in the practical supervision of MSc students.Publications:Butterworth KT, McCarthy HO, Devlin A, Ming L, Robson T, McKeown SR, Worthington J; Hypoxia selects forandrogen independent LNCaP cells with a more malignant geno- and phenotype; International Journal of Cancer,123: 760-768, 2008Devlin AH, McIlroy M, McKeen HD, Bonde P, Menezes AA, Swarbrick CJ, Robson T, Hirst DG, Campbell FC,McGuigan JA, McKeown SR; Cytochrome P450 1B1 expression in rat esophageal tumorigenesis promoted by gastricand duodenal reflux; Mol Carcinog. 2008 [Epub ahead of print]O’Keeffe MB, Devlin AH, Burns AJ, Gardiner TA, Logan ID, Hirst DG, McKeown SR. Investigation of pericytes,hypoxia, and vascularity in bladder tumors: association with clinical outcomes; Oncology Research, 17: 93-101,2008Dr Anca SmythResearch AssociateDr Smyth’s main area of interest is the study of DNA damage and repair, in particular the development of a reportergene plasmid in order to investigate specific mutagens and their mechanism of action.DNA is constantly accumulating damage from many sources and if left unrepaired this damage may result inmutations and ultimately in cancer. Several DNA repair mechanisms have been identified, each specific to the typeof damage induced by various agents. My work focuses on homologous recombination repair, base excision repairand mismatch repair.There is evidence that DNA strand breaks are the primary lethal lesions induced by ionising radiation. This damage isrepaired by two distinctive mechanisms, namely non-homologous end- joining repair and homologous recombinationrepair. The latter occurs when there are homologous sequences present in the DNA.Oxidative damage can be inflicted on the DNA through the formation of highly reactive oxygen species, generatedby endogenous metabolism or indirectly by environmental agents such as hydrogen peroxide.Frameshift mutations are the hallmark of mismatch repair defects. These events occur primarily in highly repetitivemicrosatellite regions and are characterised by the insertion or deletion of one or more repeat units, leading tomicrosatellite instability. Instability of microsatellite sequences has been reported in human colorectal cancers,particularly in hereditary non-polyposis colorectal cancer (HNPCC).We are currently working on the development of three distinctive reporter plasmids to study the three repairpathways mentioned above. All novel plasmids are non-functional variants of the Red Florescent Protein gene. Uponthe action of a specific mutagen the plasmids will revert to the functional form and fluoresce red. The plasmids could39

have wider applications in vivo, in assessing the effect of environmental carcinogens on plants or nutritional agentson colon cells.Dr Gillian WassonResearch AssociateContact Details:T: +44 (0)28 70323282gr.wasson@ulster.ac.ukDr Wasson’s main areas of interest are:Folate and CancerRecent studies have indicated that even a slight deficiency of folic acid may be a risk factor for a range of diseasesincluding cardiovascular disease, cancer and neurodegenerative diseases such as Alzheimer’s disease.However, to prove that folic acid is truly a causative factor in the disease process, it is essential to establish themechanisms underlying the suggested protective effects of folic acid. Dr Wasson has been investigating the novelresearch area of folate-dependent protein methylation. Protein methylation is a post translational modification whichmay be very important in the control of gene expression, in the early development of the body and in controllingthe structure and function of proteins. Folate is essential for the methylation of proteins and therefore proteinmethylation is a plausible mechanism through which folate may exert its effects on carcinogenesis and other diseaseprocesses.This project brings together the research areas of nutrition, cancer and proteomics to investigate an exciting andoriginal hypothesis with potentially important implications for the field of folate research. Dr Wasson is currentlyattempting to get funding to develop this research area.Werner SyndromeWerner Syndrome is a human autosomal recessive disorder characterised by the early onset of many characteristicsof normal aging and an increased risk of developing various cancers.Dr Wasson has been investigating the function of the gene responsible for Werner syndrome – in particular its rolein decatenation checkpoint control and DNA replicative integrity.Comet AssayDr Wasson is co-supervising the PhD project of Mr Darragh McArt who is developing a computational model ofthe Comet assay. This project will investigate what is happening in the Comet and Comet FISH assays at both acellular and a molecular level and has resulted in the submission of two papers, one of which is in press in the journalMutagensis.Dr Wasson was also invited to prepare a review on the use of the comet assay in the study of human nutrition andcancer which was published in Mutagenesis.40

7. DIABETES RESEARCH GROUPRESEARCH STRATEGYThe Diabetes Research Group was formed in 1989, following the appointment of Professor Peter Flatt to a Chair ofBiological & Biomedical Sciences. A significant expansion of the Group with the academic appointments of ProfessorFinbarr O’Harte (1995), Dr Neville McClenaghan (1998), Dr Aine McKillop (2002), Dr Victor Gault (2004), DrYasser Abdel-Wahab (2007), Dr Janie McCluskey (2007) and Dr Alyson Hill (2007) has strengthened the researchprofile and capitalized on the Group’s policy of research endeavour and selectivity.Since 1989 the Group has built an extensive range of external networks being the founder of the European Associationfor the Study of Diabetes (EASD) Islet Study Group and playing a pivotal role in the establishment of the EU-fundedIslet Research European and Latin-American Networks. The Group has also played a key role in diabetes researchboth nationally and internationally through senior positions in the British Diabetic Association / Diabetes UK, theEASD and establishing rich collaborations with numerous Centres of Excellence worldwide. A rich portfolio ofintellectual property has been built up in association with UUTech, leading to formation of the successful spin-outcompany Diabetica Ltd.Activities of the Group are strategically directed into five thrust areas, aiming to increase knowledge at the forefrontof diabetes research and subsequently develop new approaches for diabetes therapy:Insulin secretion and gene therapyBioengineering and proteomics of candidate insulin-secreting surrogate cells suitable for unraveling the mechanismsof pancreatic beta cell function and dysfunction and paving the way for the future gene therapy of diabetes. A majorobjective in this area is the bioengineering and proteomics of rodent and human glucose-sensitive insulin-secreting celllines. Such cells are valuable models for unraveling the mechanisms of pancreatic beta cell function and dysfunction,discovery of novel islet peptides and drug evaluation. This pioneering approach may also provide a much-neededsource of transplantable insulin-producing cells for the gene therapy of diabetes.Antidiabetic actions of structurally modified peptidesInvestigating the impact of structural modification of biologically active brain-gut peptides on the regulation offeeding, pancreatic beta cell function and anti-hyperglycaemic activity. The focus of this research is to evaluate theimpact of structural modification of biologically active brain-gut peptides on satiety, insulin-releasing activity andantihyperglycaemic potential. This work has culminated in the synthesis of a number of novel biologically potentenzyme-resistant peptide analogues for potential obesity-diabetes therapy. Clinical investigations are underway.Discovery, targets and action of antidiabetic drugsCharacterization of novel antidiabetic agents, isolation of new compounds from natural sources, elucidation of theirsites and modes of action and potential therapeutic role in correcting insulin secretion and action in diabetes. Thisresearch is directed towards discovery, isolation and characterization novel antidiabetic agents from natural sources,including plants and amphibian venoms. Work extends to elucidation of the sites and modes of action of novelchemical entities. A major part of this research also evaluates actions of both established and new generations ofantidiabetic drugs including the sulphonylureas and imidazolines. These studies are continuing to reveal importantnovel beta-cell drug targets.Mechanisms of pancreatic beta-cell dysfunction and insulin glycationInvolvement of glucose, lipid and drug toxicity and glycation of insulin and other pancreatic beta cell proteins ininsulin secretory dysfunction, insulin resistance and pathogenesis of diabetes. The major thrust in this area concernsthe role of glucose, lipid, drug toxicity and glycation of pancreatic beta-cell proteins in the development of insulinsecretory dysfunction, insulin resistance and type 2 diabetes. One highlight is the discovery that pancreatic beta-cellssecrete glycated insulin, which through impaired biological activity contributes to insulin resistance. Clinical studiesare underway using a novel and specific assay for glycated insulin developed in our laboratory.41

Inter-relationships between diet and diabetes/obesityAssessment of diet and lifestyle factors in gestational type 1 and type 2 diabetes. This research aims toassess what women with diabetes eat in relation to lifestyle and published dietary guidelines. A further element isassessing maternal diet and lifestyle factors in relation to gestational diabetes and pregnancy outcomes.The overall strategy of the Diabetes Research Group is:• to undertake and publish research of national and international status aimed at increasing knowledge of thepancreatic islets, endocrine control of nutrient homeostasis and both the pathophysiology and treatment ofdiabetes mellitus;• to exploit intellectual property and actively pursue technology transfer with the aim of helping to alleviate theworld-wide burden of diabetes and contributing to the prosperity and knowledge-based economy in NorthernIreland;• to provide a supportive and high quality training environment for research students and postdoctoral fellows tofacilitate the acquisition of knowledge, new skills, personal fulfillment and career progression;• to participate in productive national and international networks with Centres of Excellence for diabetesresearch and to actively contribute to the global diabetes community, through conferences and involvementwith organizations promoting research, understanding and well being of individuals with diabetes.Members of the GroupAcademic Staff:Group LeaderProfessor of Biological & Biomedical SciencesContact Details:T: +44 (0)28 70324419pr.flatt@ulster.ac.ukBrief Profile:BSc Hons and PhD from Aston University. Research Fellow at the University of Uppsala, Sweden (1978-80) beforetaking up an academic appointment at Surrey University in 1980 and current position as Professor of BiomedicalSciences in 1989. Professor Flatt is Head of the Diabetes Research Group, having served as Director of BiomedicalSciences Research Centre (1992-94) and Head of the School of Biomedical Sciences (1994-97).Professor Flatt is author of over 400 full scientific peer-reviewed papers on various aspects of diabetes and editorof 4 major diabetes research texts including New Antidiabetic Drugs (Smith-Gordon, 1990) and Nutrient Regulationof Insulin Secretion (Portland Press, 1992).He is founding Chairman (1991-) of the Islet Study Group of the European Association for the Study of Diabetes(EASD), Member of the EASD Council (1997-01), Scientific Secretary and Committee Member of Diabetes UK(1991-97; 2001-04) and member of the Grants Review Board of the Juvenile Diabetes Federation International(1996-99).Recipient: Mary Jane Kugal Award (1999) of Juvenile Diabetes Federation International, Biochemical Society Medal(2005), elected to membership of Royal Irish Academy (2006), University of Ulster Distinguished Senior ResearchFellowship (2006) and Diabetes UK Dorothy Hodgkin Award Lecturer (2008). Patent holder - academic co-founder42

and Chief Scientific Officer/Director of Diabetica Limited.Main Research interests:• Insulin secretion• pancreatic islet cell function and demise• antidiabetic drugs• gene therapy• brain and gut peptides• glucose homeostasis• insulinoma and obesity.Esteem:2007 Hodgkin Award presented at the Annual Professional Congress of Diabetes UKCommittees:Member of Diabetes UK Advisory CouncilMember of Diabetes UK Research CommitteeMember of Diabetes UK Research Advisory GroupMember of Diabetes UK Professional Advisory CouncilMember of Diabetes UK Science and Research CommitteeFounding Chairman European Association for Study of Diabetes (EASD) Islet Study GroupFounding Member of Islet Research European and Latin American NetworksMember of Executive of IRELAN Alfa NetworkChairman, scientific sessions at Diabetes UK, EASD and other International meetingsConsultant to Shering PloughInvited LecturesSeminar on Novel Approaches to Diabetes Therapy, Takeda Pharmaceuticals, Amsterdam, 2007Oxford Centre for Diabetes Endocrinology and Metabolism (OCDEM) Seminar Series Guest Lecture , Oxford, 2007Seminar on GIP Therapeutics and Diabetes, Boehringer Ingelheim Pharmaceutical Company, Biberach, Germany, 2007International Conference on Treatment and Prevention of Obesity, Copenhagen, 2007Seminar on Incretin Hormones and Diabetes, Organon Pharmaceutical Company, Oss, Netherlands, 2007Seminar on Therapeutic Gut Hormones, Novo Nordisk Ltd, Copenhagen, 2007Conference on New Approaches to Diabetes, Ipsen Pharmaceutical Company, Barcelona, 2007International Conference on Diabetes in Crisis, Dublin, 2007Diabetes UK Annual Professional Congress, Dorothy Hodgkin Lecture, Glasgow, 2008Diabetes UK Annual Professional Congress, Meet the Professor, Glasgow, 2008International Conference on Importance of Early Phase Insulin Release in Type 2 Diabetes, Tokyo, 2008International Conference on Diabetes Mellitus and Obesity, Taif, Saudi Arabia, 2008FEND (Federation of European Nurses in Diabetes) 13th Annual Conference, Rome, September, 2008Royal Society of Medicine Conference on From Bench to Patient: taking Diabetes into the 21st Century, London,October, 2008Publications:Abdel-Wahab YHA, Marenah L, Flatt PR and Conlon JM; Insulin-releasing properties of the temporin family ofantimicrobial peptides; Protein Pept. Letts, 14: 702-707, 2007Duffy NA, Green BD, Irwin N, Gault VA, McKillop AM, O’Harte FPM and Flatt PR; Effects of antidiabetic drugson dipeptidyl peptidase IV activity: Nateglinide is an inhibitor of DPP IV and augments the antidiabetic activity ofglucagon-like peptide-1; European Journal of Pharmacology, 568: 278-286, 200743

Flatt PR; Effective surgical treatment of obesity may be mediated by ablation of the lipogenic gut hormone gastricinhibitory polypeptide (GIP): Evidence and clinical opportunity for development of new obesity-diabetes drugs?;Diab. Vasc. Dis. Res., 4: 151-153, 2007Irwin N, Hunter K and Flatt PR; Comparison of the sub-chronic metabolic effects of GIP receptor antagonism andPYY(3-36) receptor activation in high fat fed mice; Peptides, 28: 2192-2198, 2007Kiely A, McClenaghan NH, Flatt PR and Newsholme P; Pro-inflammatory cytokines increase glucose, alanineand triacylglycerol utilization but inhibit insulin secretion in a clonal pancreatic beta-cell line; Journal ofEndocrinology, 195: 113-123, 2007Liu HK, McCluskey JT, McClenaghan NH and Flatt PR; Streptozotocin-resistant BRIN-BD11 cells possess wide spectrumof toxin tolerance and enhanced insulin-secretory capacity; Endocrine, 32: 20-29, 2007McClean PL, Irwin N, Cassidy RS, Holst JJ, Gault VA and Flatt PR; GIP receptor antagonism using (Pro 3 )GIP reverses obesity,insulin resistance and associated metabolic disturbances induced in mice by prolonged consumption of high fat diet;American Journal of Physiology, 293: E1746-1755, 2007Abdel-Wahab YHA, Power GJ, Ng MT, Flatt PR and Conlon MJ; Insulin-releasing properties of the frog skinpeptide pseudin-2 and its [Lys18]-substituted analogue; Biol. Chem., 389: 143-148, 2008Abdel-Wahab YHA, Power GJ, Flatt PR, Woodhams DC, Rollins-Smith LA and Conlon JM; A peptideof thephylloeptin family from the skin of the frog Hylomantis lemur (Phyllomedusinae) with potent in vitro and invivo insulin-releasing activity; Peptides, 29: 2136-2143, 2008Cassidy RS, Irwin N and Flatt PR; Effects of gastric inhibitory polypeptide (GIP) and related analogues on glucagon releaseat normo- and hyperglycaemia in Wistar rats and isolated islets; Biol. Chem., 389: 189-193, 2008Conlon JM, Power GJ, Abdel-Wahab YHA, Flatt PR, Jiansheng H, Coquet L, Leprince J, Jouenne T and VaudryH; A potent non-toxic insulin-releasing peptide isolated from an extract of the skin of the Asian frog,Hylarana guntheri (Anura: Ranidae); Regulatory Peptides, 151: 153-159, 2008Gault VA, Kerr BD, Irwin N and Flatt PR; C-terminal mini-PEGylation of glucose-dependent insulinotropicpolypeptide exhibits metabolic stability and improved glucose homeostasis in ietary-induced diabetes;Biochem. Pharmacol. 75: 2325-2333; 2008.Irwin N, Hunter K and Flatt PR; Comparison of independent and combined metabolic effects of GIP andCB1 receptor blockade in high-fat fed mice; Peptides, 29: 1036-1041, 2008Irwin N, Hunter K, Frizzell N and Flatt PR; Antidiabetic effects of sub-chronic administration of the cannabinoidreceptor (CB1) antagonist, AM251, in obese diabetic (ob/ob) mice; European Journal of Pharmacology, 581:226-233, 2008Liu HK, McCluskey JT, McClenaghan NH and Flatt PR; Interative exposure of clonal BRIN-BD11 cellsto ninhydrin enables selection of robust toxin-resistant pancreatic beta cells but with decreased geneexpression and insulin-secretory function; Pancreas, 36: 294-301, 2008McClean PL, Irwin N, Hunter K, Gault VA and Flatt PR; (Pro 3 )GIP[mPEG]: Novel long-acting mini-PEGylatedgastric inhibitory polypeptide antagonist for obesity-diabetes therapy; British Journal of Pharmacology, 155:690-701, 2008McKillop AM, Duffy NA, Lindsay JR, O’Harte FPM, Bell P and Flatt PR; Decreased dipeptidyl peptidase IVactivity and GLP-1 degradation in type 2 diabetic subjects; Diabetes Clin. Res. Pract, 79: 79-85, 200844

Taylor A, Irwin N, McKillop AM, Flatt PR and Gault VA; Sub-chronic administration of 11beta-HSD1 inhibitor,carbenoxolone, improves glucose tolerance and insulin insensitivity in mice with diet-induced obesity; Biol.Chem., 389: 441-445, 2008Irwin N, McClean PL, Hunter K & Flatt PR (2009) Metabolic effects of sustained activation of the GLP-1 receptoralone and in combination with background GIP receptor antagonism in high fat fed mice. Diabetes, Obesity and Metabolism(in press)Irwin N, Hunter K, Frizzell N and Flatt PR; Antidiabetic effects of sub-chronic up-regulation of the GIP receptor aloneand in combination with background exendin-4 therapy in high fat fed mice; Reg. Pept. (in press)Kerr BD, Irwin N, Flatt PR and Gault VA; Prolonged GIP receptor activation using stable mini-PEGylated GIP improvesglucose homeostasis and beta cell function in age-related glucose intolerance; Peptides (in press)McClenaghan NH, Scullion SM, Mion N, Hewage C, Malthouse JPG, Flatt PR, Newsholme P and Brennan L; Prolongedalanine exposure induces changes inmetabolism, Ca 2+ handling and desensitization of insulin secretion in clonalpancreatic beta cells; Clin. Sci. (in press)Professor FPM O’HarteProfessor of Endocrinology & MetabolismContact details:T: +44 (0)28 70324853fpm.oharte@ulster.ac.ukBrief profile:BSc Hons and PhD from Queen’s University Belfast. Research Fellow at Creighton University, Omaha, USA (1989-91),University College Cork (1992-93) and University of Ulster (1993-95) before taking up an academic appointmentat the University of Ulster in 1995. Promoted to Reader in 2000 and Professor of Endocrinology and Metabolismin 2005. Patent holder and academic co-founder of Diabetica Limted, a UU start-up company focused on innovativediabetes therapeutics. Over 180 peer-reviewed publications with many presentations at national and internationalconferences and was recipient of the Nordisk Medal of the Irish Endocrine Society (2005).Main Research interests:• structurally modified peptides in therapy and drug development• role of regulatory peptides in control of feeding and obesity• incretin hormone analogues in diabetes therapy• structure-function activity of peptides• hormone receptor modelling and NMR• glucagon receptor antagonists in diabetes therapy.Professor O’Harte’s main research interests include investigations into the impact of structural modification ofbiologically active brain-gut peptides on the regulation of feeding, pancreatic beta cell function and anti-hyperglycaemicactivity. This work has focused in the synthesis of a numerous novel biologically active and enzyme-resistant long-actingpeptide analogues for potential obesity-diabetes therapy. Modifications of the antidiabetic incretin hormones GLP-1and GIP as well as the anti-obesity hormone CCK-8 leading to enhanced biological action of these agents formedthe main focus of this work. However, preliminary work was also performed to assess the potential of peptide-basedglucagon receptor antagonists as novel antidiabetic agents. Pre-clinical investigations are at an advanced stage withthe GIP based agents.45

These areas are the subject of several national and international patents. Patents linked to stable GIP receptoragonists have been licensed to a major USA based pharmaceutical company through the spin-out company DiabeticaLtd. It is hoped that clinical studies will start shortly and ultimately lead to new agents for diabetes therapy which willhave a significant impact on the end users.Indicators of Research Esteem:Member of the Editorial Board of British Journal of Pharmacology (2005-2009)Member of the Editorial Board of Journal of Endocrinology (2004-2009)Member of committee for Irish Endocrine Society (2006-present)Member of HPSS R&D Office Clinical Research Fellowship Review Panel (2005-2007)Professor O’Harte is a co-founder with 4 other selected academic/clinical colleagues in the UK of a unique advancedtraining program entitled Innovators in Diabetes (IDia) for young research scientists and clinicians working in thediabetes field in the UK and N. Ireland (rolling program 2008-onwards). The inaugural meeting for this initiativesponsored by a Novo Nordisk education grant was held at the Barnsdale Lodge Hotel near Oakham, Rutland, UK for3 days (8-10 May 2008 inclusive) and will continue annually in May 2009 and thereafter.Publications:Alana I, Malthouse JP, O’Harte FPM and Hewage CM; The bioactive conformation of glucose-dependent insulinotropicpolypeptide by NMR and CD spectroscopy; Proteins: Structure, Function and Bioinformatics, 68: 92-99, 2007Duffy NA, Green BD, Irwin N, Gault VA, McKillop AM, O’Harte FPM and Flatt PR; Effects of antidiabetic drugson dipeptidyl peptidase IV activity: Nateglinide is an inhibitor of DPP IV and augments the antidiabetic activity ofglucagons-like peptide-1; European Journal of Pharmacology, 568: 278-286, 2007Irwin N, McClean PL, Cassidy RS, O’Harte FPM, Green BD, Gault VA, Harriott P and Flatt PR; Comparison of the antidiabeticeffects of GIP- and GLP-1-receptor activation in obese diabetic (ob/ob) mice: studies with DPP IV resistantN-AcGIP and exendin(1-39)amide; Diabetes Metab. Research Reviews, 23: 572-579, 2007Irwin N, McClean PL, O’Harte FPM, Gault VA, Harriott P and Flatt PR; Early administration of the glucosedependentinsulinotropic polypeptide receptor antagonist (Pro 3 )GIP prevents the development ofdiabetes and related metabolic abnormalities associated with genetically inherited obesity in ob/ob mice;Diabetologia, 50: 1532-1540, 2007McKillop AM, Duffy NA, Lindsay JR, O’Harte FPM, Bell PM and Flatt PR; Decreased dipeptidyl peptidase-IV activityand glucagon-like peptide-1(7-36)amide degradation in type 2 diabetic subjects; Diab. Res. Clin. Pract, 79: 79-85, 2008Dr NH McClenaghanHead of School of Biomedical SciencesContact details:T: +44 (0)28 70323011nh.mcclenaghan@ulster.ac.ukBrief profile:Conducted research at the University of Uppsala, Sweden (1991-92) before graduating with a BSc Hons and PhDfrom the University of Ulster. Research Fellow at Hannover Medical School (1996-98), before taking up an academicappointment at the University of Ulster in 1998. Promoted to Senior Lecturer and recipient of University of UlsterDistinguished Research Fellowship Award in 2001. Dr McClenaghan has over 110 peer-reviewed publications, hasbeen invited to speak at many national and international conferences. Patent holder, academic co-founder and ChiefOperating Officer of Diabetica Limted, a UU start-up company focused on innovative diabetes therapeutics.46

Main research interests:• Bioengineering pancreatic beta cells• stimulus-secretion coupling mechanisms• beta cell metabolism• ionic modulation of islet cell function• signal transduction pathways• apoptosis and mechanisms of beta cell demise and destruction• novel beta cell drug targets• actions of new insulinotropic antidiabetic agents• insulinotropic drug desensitization.Neville is Co-Founder, Stakeholder and Chief Operating Officer (COO) of spinout company Diabetica Limited,driving company development, operations and planning. He has managed an extensive patent portfolio and engagedwith corporate financiers, venture capital groups and major pharmaceutical and biotech companies for exploitationof novel IP, negotiating R&D and license agreements (~£23M to date). Neville is a named inventor, and author ofgrowing patent estate (comprising 11 national and international patents), has acted as consultant/advisor to numberof private and public sector clients and organizations, and is strongly committed to entrepreneurship, stimulation ofenterprise and creativity, wealth creation, and the knowledge-based economy.Neville has been recipient of a number of awards for research and academic enterprise activities and his primaryresearch interests are: bioengineering pancreatic islet cells; actions of anti-diabetic drugs and drug-induced beta-celldesensitization; tracing novel metabolic and beta-cell secretory pathways; and chronic detrimental beta-cell actionsof nutrients and the diabetic environment. Neville is author of over 50 published scientific papers; invited lecturer,chairperson/facilitator at numerous research and business conferences and meetings; and has regularly facilitatedpublic and private sector discussion and education on academic enterprise and in particular R&D for diabetes andobesity.Publications:Liu HK, McCluskey JT, McClenaghan NH, Flatt PR; Streptozotocin-resistant BRIN-BD11 cells possess a wide spectrumof toxin tolerance and enhanced insulin-secretory capacity; Endocrine, 32: 20-29, 2007Patterson S, Scullion SM, McCluskey JT, Flatt PR, McClenaghan NH; Prolonged exposure to homocysteine resultsin dimished but reversible pancreatic beta-cell responsiveness to insulinotropic agents. Diabetes Metab. Res. Rev.,23(4):324-334, 2007Liu HK, McCluskey JT, McClenaghan NH, Flatt PR; Iterative exposure of clonal BRIN-BD11 cells to ninhydrin enablesselection of robust toxin-resistant cells but with decreased gene expression of insulin secretory function; Pancreas,36: 294-301, 200847

Dr YHA Abdel-WahabSenior Lecturer in Biomedical SciencesContact details:+44 (0)28 70324354y.abdel-wahab@ulster.ac.ukBrief profile:MB. BCh. (1985), Faculty of Medicine, Cairo University, Egypt and PhD (1993) from University of Ulster,Coleraine. Postdoctoral Research Fellow at Creighton University, School of Medicine, USA (1994-95),Postdoctoral Researcher at the University of Ulster at Coleraine (1995-2007) before taking up current appointmentas Senior Lecturer in Biomedical Sciences at the University of Ulster in 2007. Dr Abdel-Wahabhas over 60 peer-reviewed publications, invited speaker at many national and international conferences andis a Patent holder.Main research interests:Discovery, targets and action of antidiabetic drugs from natural resourcesAntidiabetic actions of structurally modified peptidesGlycation of pancreatic islet peptides and proteinsStem cell and gene therapy in diabetes.Publications:Abdel-Wahab YHA, Maranah L, Flatt PR, Conlon JM; Insulin releasing properties of the temporin family of antimicrobialpeptides; Europe Protein & Peptide Letters, 14: 702-707, 2007Hannan JMA, Marenah L, Ali L, Rokeya B, Flatt PR and Abdel-Wahab YHA; Insulin secretory actions of extracts ofAsparagus racemosus root in perfused pancreas, isolated islets and clonal pancreatic B-cells; Journal of Endocrinology,192: 159-168, 2007Hannan JMA, Ali L, Rokeya B, Khaleque J, Akhter M, Flatt PR and Abdel-Wahab YHA; Soluble dietary fibre fraction ofTrigonella foenum-graecum (fenugreek) seed improves glucose homeostasis in type 1 and type 2 diabetes by delayingcarbohydrate digestion, absorption and enhancing insulin action; British Journal of Nutrition, 97: 514-521, 2007Abdel-Wahab YHA, Power GJ, Ng MT, Flatt PR, Conlon JM; Insulin-releasing properties of the frog skin peptidepseudin-2 and its [Lys 18 ] substituted analogue; Biological Chemistry, 389: 143-148, 2008Abdel-Wahab YHA, Power GJ, Flatt PR, Woodhams DC, Rollins-Smith LA, Conlon JM; A peptide of thephylloseptin family from the skin of the frog Hylomantis lemur (Phyllomedusinae) with potent in vitro and invivo insulin-releasing activity; Peptides, 29: 2136-2143, 2008Conlon JM, Power GJ, Abdel-Wahab YHA, Flatt PR, Jiansheng H, Coquet L, Leprince J, Jouenne T, Vaudry H; Apotent, non-toxic insulin-releasing peptide isolated from an extract of the skin of the Asian frog, Hylarana güntheri(Anura:Ranidae); Regulatory peptides, 151: 153-159, 2008Conlon JM, Abdel-Wahab YHA, Flatt PR, Leprince J; A glycine-leucine-rich peptide structurally related to the plasticinsfrom skin secretions of the frog Leptodactylus laticeps (Leptodactylidae); Peptides (in press)48

Dr AM McKillopSenior Lecturer in Clinical & Endocrine BiochemistryContact Details:T: +44 (0)28 70323066am.mckillop@ulster.ac.ukBrief profile:BSc Hons and PhD from Queen’s University, Belfast and MSc from the University of Ulster. PostdoctoralResearch Fellow at Queen’s University, Belfast (1996-98) and the University of Ulster at Coleraine (1998-02) before taking up current appointment as Lecturer in Clinical Biochemistry at the University of Ulster in2002. Patent holder and over 40 peer-reviewed publications and presentations at national and internationalconferences.Main research interests:• clinical biochemistry and diabetes proteomics• cellular glucose handling and metabolism• pancreatic beta-cell peptides and proteins• mechanisms of insulin resistance and diabetes pathogenesis• glycation of insulin and other key regulatory proteins• structural and functional characterization of novel biomolecules• insulin receptor dysfunction and novel treatments for diabetes.During the year under review, Dr McKillop obtained a pilot grant (£10,000) from the University “Pre-Proof ofConcept Scheme” to support a recently successful application to Invest Northern Ireland for a Proof of Conceptgrant (£70,340) to investigate: “Intestinal Biomarkers for Diabetes”.Publications:Duffy N, Green BD, Irwin N, Gault VA, McKillop AM, O’Harte FPM, Flatt PR; Effects of antidiabetic drugs in dipeptidylpeptidase IV: Nateglinide is an inhibitor of DPPIV and augments antidiabetic activity of glucagon-like peptide-1;European Journal of Pharmacology, 568: 278-286, 2007McKillop AM, Duffy NA, Lindsay JR, O’Harte FPM, Bell PM, Flatt PR; Decreased dipeptidyl peptidase-IV activity andglucagon-like peptide-1(7-36)amide degradation in type 2 diabetic subjects; Diabetes Res Clin Pract., 79: 79-85, 2008McKillop, AM., Flatt PR; Recent Developments in the Search for Biomarkers for the Diagnosis and Monitoring ofDiabetes; Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 2: 172-177, 2008Taylor A, Irwin N, McKillop AM, Flatt PR, Gault VA; Sub-chronic administration of 11beta-HSD1 inhibitor, carbenoxolone,improves glucose tolerance and insulin sensitivity in mice with diet-induced obesity; Biological Chemistry, 389: 441-445,200849

Dr VA GaultLecturer in Molecular BiosciencesContact details:T: +44 (0)28 70323322va.gault@ulster.ac.ukBrief profile:BSc Hons from Queen’s University of Belfast and PhD from University of Ulster. Research Associate at the Universityof Ulster (2002-04) before taking up current appointment as Lecturer in Molecular Biosciences at the University ofUlster in 2004.Patent holder and over 120 peer-reviewed publications and presentations at national and international conferencesand was recipient of the highly-prestigious Eli-Lilly Basic Science Research Award in 2003, University of Ulster DistinguishedResearch Fellowship Award in 2005 and Diabetes UK Young Investigator Award in 2008. Plays an activerole in Research Group publicity.Main research interests:The central theme of Dr Gault’s research is directed towards the prevention and treatment of degenerativedisease states, particularly diabetes and related metabolic disorders. Recent work has also focused onaspects of neurodegenerative processes.His focus research interests include:• Discovery, design, characterisation / validation and pharmacological evaluation of novel peptide-basedtherapeutics.• Insulin signalling, neuronal activity and cognitive behaviour.Control HF HF + GIPAntagonistAdiposeLiverEffects of daily (160 days) administration of a novel GIP antagonist on whiteadipose tissue and liver morphology in Swiss TO mice fed a high fat diet.Following treatment, adipocyte size and liver morphology were particallynormalised. Representative images are original magnification x20.Taken from Gault et al. Diabetologia 50: 1752-1762, 2007.50

Current projects include:• Development of novel, long-acting glucose-dependent insulinotropic (GIP) receptor antagonists for the treatmentof diabetes and obesity.• Assessment of the antihyperglycaemic and insulinotropic actions of the peptide Xenin and related analogues.• Effects of incretin mimetics on insulin signalling, neuronal activity and cognitive behaviour in diabetes.• Evaluation of insulin-like drugs as a potential therapeutic for Alzheimer’s disease (in collaboration with DrChristian Holscher, neurobiology research group).Achievements and outputs over the reporting period:• Publication of 5 peer-reviewed abstract communications presented at national / international conferences.• Recipient of Young Investigator Award for Outstanding contribution to basic and clinical science research,Diabetes UK.• Co-applicant on successful external grant applications totalling £248,484 from Alzheimer’s Research Trust andAlzheimer’s Research Society.• Invited as Editor-in-Chief: Clinical Medicine – Endocrinology and Diabetes.• Filing of 2 patents on the use of incretin peptides for the treatment of disorders associated with dysfunctionalsynaptic transmission.• Successful completion of 1 PhD and 1 MRes student.Publications:Duffy NA, Green BD, Irwin N, Gault VA, McKillop AM, O’Harte FPM and Flatt PR; Effects of antidiabetic drugson dipeptidyl peptidase IV activity: Nateglinide is an inhibitor of DPP IV and augments the antidiabetic activity ofglucagon-like peptide-1;European Journal of Pharmacology, 568: 278-286, 2007Gault VA, McClean PL, Irwin N, Power GJ, McCluskey JT, Flatt PR; Effects of subchronic treatment with the long-actingglucose-dependent insulinotropic polypeptide receptor agonist, N-AcGIP, on glucose homeostasis in streptozotocininduceddiabetes; Pancreas, 35: 73-79, 2007Gault VA, Hunter K, Irwin N, Green BD, Greer B, Harriott P, O'Harte FP, Flatt PR; Characterisation and biological activityof Glu 3 amino acid substituted GIP receptor antagonists; Archives of Biochemistry Biophysics, 461: 263-274, 2007Gault VA, McClean PL, Cassidy RS, Irwin N, Flatt PR; Chemical gastric inhibitory polypeptide receptor antagonismprotects against obesity, insulin resistance, glucose intolerance and associated disturbances in mice fed high-fat andcafeteria diets; Diabetologia, 50: 1752-1762, 2007Irwin N, McClean PL, Cassidy RS, O’Harte FPM, Green BD, Gault VA, Harriott P and Flatt PR; Comparison of the antidiabeticeffects of GIP- and GLP-1-receptor activation in obese diabetic (ob/ob) mice: studies with DPP IV resistantN-AcGIP and exendin(1-39)amide; Diabetes Metab. Research Reviews, 23: 572-579, 2007Irwin N, McClean PL, O’Harte FPM, Gault VA, Harriott P and Flatt PR; Early administration of the glucosedependentinsulinotropic polypeptide receptor antagonist (Pro 3 )GIP prevents the development ofdiabetes and related metabolic abnormalities associated with genetically inherited obesity in ob/ob mice;Diabetologia, 50: 1532-1540, 2007McClean PL, Irwin N, Cassidy RS, Holst JJ, Gault VA and Flatt PR; GIP receptor antagonism using (Pro 3 )GIP reversesobesity, insulin resistance and associated metabolic disturbances induced in mice by prolonged consumption of highfat diet; American Journal of Physiology, 293: E1746-1755, 2007O'Harte FP, Hunter K, Gault VA, Irwin N, Green BD, Greer B, Harriott P, Bailey CJ, Flatt PR; Antagonistic effects oftwo novel GIP analogues, (Hyp 3 )GIP and (Hyp 3 )GIPLys 16 PAL on the biological actions of GIP and longer term effectsin diabetic ob/ob mice; American Journal of Physiology Endocrinology and Metabolism, 292: E1674-1682, 2007Gault VA, Kerr BD, Irwin N and Flatt PR; C-terminal mini-PEGylation of glucose-dependent insulinotropic polypeptideexhibits metabolic stability and improved glucose homeostasis in ietary-induced diabetes; Biochem. Pharmacol. 75:2325-2333; 2008.51

McClean PL, Irwin N, Hunter K, Gault VA and Flatt PR; (Pro 3 )GIP[mPEG]: Novel long-acting mini-PEGylated gastricinhibitory polypeptide antagonist for obesity-diabetes therapy; British Journal of Pharmacology, 155: 690-701, 2008Taylor A, Irwin N, McKillop AM, Flatt PR and Gault VA; Sub-chronic administration of 11beta-HSD1 inhibitor,carbenoxolone, improves glucose tolerance and insulin insensitivity in mice with diet-induced obesity; Biol. Chem.,389: 441-445, 2008Kerr BD, Irwin N, Flatt PR and Gault VA; Prolonged GIP receptor activation using stable mini-PEGylated GIP improvesglucose homeostasis and beta cell function in age-related glucose intolerance; Peptides (in press)Dr JT McCluskeyLecturer in Biomedical SciencesContact details:T: +44 (0)28 70324882jt.mccluskey@ulster.ac.ukBrief profile:BSc Hons from University of Glasgow (1991) and DPhil from University of Oxford (1995) in Developmental andCellular Biology. Postdoctoral Research at King’s College London (1995 – 1997), University College London (1997-1998) and University of Ulster (1998 – 2007) prior to taking up present position as Lecturer in Biomedical Sciencesat the University of Ulster, Coleraine (2007). Over 30 peer-reviewed publications and invited speaker at internationaland national conferences.Main research interests:• Cellular and molecular events in novel human and rodent insulin-secreting pancreatic beta cell lines• Formation of pancreatic endocrine cells from embryonic stem cells• Glucose and lipid toxicity, drug sensitisation, and actions of cytotoxic agentsPublications:Liu HK, McCluskey JT, McClenaghan NH, Flatt PR; Streptozotocin-resistant BRIN-BD11 cells possess a wide spectrumof toxin tolerance and enhanced insulin-secretory capacity; Endocrine, 32: 20-29, 2007Gault VA, McClean PL, Irwin N, Power GJ, McCluskey JT, Flatt PR; Effects of subchronic treatment with the long-actingglucose-dependent insulinotropic polypeptide receptor agonist, N-AcGIP, on glucose homeostasis in streptozotocininduceddiabetes; Pancreas, 35: 73-79, 2007Patterson S, Scullion SM, McCluskey JT, Flatt PR, McClenaghan NH; Prolonged exposure to homocysteine resultsin dimished but reversible pancreatic beta-cell responsiveness to insulinotropic agents. Diabetes Metab. Res. Rev.,23(4):324-334, 2007Liu HK, McCluskey JT, McClenaghan NH, Flatt PR; Iterative exposure of clonal BRIN-BD11 cells to ninhydrin enablesselection of robust toxin-resistant cells but with decreased gene expression of insulin secretory function; Pancreas,36: 294-301, 2008McClean PL, Gault VA, Irwin N, McCluskey JT, Flatt PR; Daily administration of the GIP-R antagonist (Pro3)GIP instreptozotocin-induced diabetes suggests that insulin-dependent mechanisms are critical to anti-obesity diabetesactions of (Pro3)GIP; Diabetes Obes. Metab., 10: 336-342, 200852

Dr A HillLecturer in DieteticsContact details:T: +44 (0)28 70324128aj.hill@ulster.ac.ukBrief profile:Qualified with BSc Dietetics in Queen Margaret Edinburgh. MSc and PhD Huma n Nutrition from University of Ulster.Worked as a clinical dietitian for 16 years mainly in Royal Hospitals Belfast specialising in dietary management ofadults with diabetes before taking up a post as Lecturer in Dietetics in University of Ulster 2006.Clinical research links:Collaborate with diabetic physicians in Royal Hospitals, Belfast on local arm of:• Hyperglycaemia and Adverse Pregnancy Outcome Study (HAPO)• Diabetes and Pre-eclampsia Intervention Study (DAPIT).Main research interests:• Dietary management of pregnant women with diabetes in relation to pregnancy outcomes• Relationships between diet and glycaemic control in those who develop gestational diabetes.Research Staff:Dr N IrwinResearch Fellow in DiabetesContact details:T: +44 (0)28 70324313n.irwin@ulster.ac.ukBrief profile:BSc Hons and PhD from University of Ulster. Research Associate at the University of Ulster (2004-07) before takingup current appointment as Research Fellow in Diabetes at the University of Ulster in 2007. Dr Irwin is a patentholder and author of over 80 peer-reviewed publications and an invited speaker at international and national conferences.Main research interests:• Therapeutic development of human peptide hormones• Glucose homeostasis in aging• Hormonal regulation of feeding/obesityDuring the year under review, Dr Irwin obtained funding of £5000 from the PhD Studentship Top-up Schemesponsored by the Health and Personal Social Services Research and Development Office (NI) to provide additionalsupport a PhD project entitled “Assessment of the potential of GIP receptor antagonism for diabetes therapy”. He alsoobtained pilot funding of £9,780 (jointly with Professor Finbarr O’Harte) through the University’s Research CouncilSupport Fund for a project entitled: “Evaluation of novel glucagons receptor antagonists for diabetes therapy”.53

Publications:Duffy NA, Green BD, Irwin N, Gault VA, McKillop AM, O'Harte FP, Flatt PR; Effects of antidiabetic drugs on dipeptidylpeptidase IV activity: Nateglinide is an inhibitor of DPP IV and augments the antidiabetic activity of glucagon-likepeptide-1; European Journal of Pharmacology, 568: 278-286, 2007Gault VA, Hunter K, Irwin N, Green BD, Greer B, Harriott P, O'Harte FP, Flatt PR; Characterisation and biological activityof Glu 3 amino acid substituted GIP receptor antagonists; Archives of Biochemistry Biophysics, 461: 263-274, 2007Gault VA, McClean PL, Irwin N, Power GJ, McCluskey JT, Flatt PR; Effects of subchronic treatment with the long-actingglucose-dependent insulinotropic polypeptide receptor agonist, N-AcGIP, on glucose homeostasis in streptozotocininduceddiabetes; Pancreas, 35: 73-79, 2007Gault VA, McClean PL, Cassidy RS, Irwin N, Flatt PR; Chemical gastric inhibitory polypeptide receptor antagonismprotects against obesity, insulin resistance, glucose intolerance and associated disturbances in mice fed high-fat andcafeteria diets; Diabetologia, 50: 1752-1762, 2007Green BD, Irwin N, Flatt PR; Direct and indirect effects of obestatin peptides on food intake and the regulation ofglucose homeostasis and insulin secretion in mice; Peptides, 28: 981-987, 2007Irwin N, McClean PL, Cassidy RS, O'Harte FP, Green BD, Gault VA, Harriott P, Flatt PR; Comparison of the antidiabeticeffects of GIP- and GLP-1-receptor activation in obese diabetic (ob/ob) mice: studies with DPP IV resistantN-AcGIP and exendin(1-39)amide; Diabetes Metabolism Research and Reviews, 23: 572-579, 2007Irwin N, Hunter K, Flatt PR; Comparison of the metabolic effects of GIP receptor antagonism and PYY(3-36) receptoractivation in high fat fed mice; Peptides, 28: 2192-2198, 2007Irwin N, McClean PL, O'Harte FP, Gault VA, Harriott P, Flatt PR; Early administration of the glucose-dependent insulinotropicpolypeptide receptor antagonist (Pro( 3 ))GIP prevents the development of diabetes and related metabolicabnormalities associated with genetically inherited obesity in ob/ob mice; Diabetologia, 50: 1532-1540, 2007Irwin N, McClean PL, Flatt PR; Comparison of the subchronic antidiabetic effects of DPP IV-resistant GIP and GLP-1analogues in obese diabetic (ob/ob) mice; Journal of Peptide Science, 13: 400-405, 2007Irwin N, McClean PL, Harriott P, Flatt PR; Beneficial effects of sub-chronic activation of glucagon-like peptide-1 (GLP-1) receptors on deterioration of glucose homeostasis and insulin secretion in aging mice; Experimental Gerontology,42: 296-300, 2007McClean PL, Irwin N, Cassidy RS, Holst JJ, Gault VA, Flatt PR; GIP receptor antagonism reverses obesity, insulin resistanceand associated metabolic disturbances induced in mice by prolonged consumption of high fat diet; AmericanJournal of Physiology Endocrinology and Metabolism, 293: E1746-1755, 2007O'Harte FP, Hunter K, Gault VA, Irwin N, Green BD, Greer B, Harriott P, Bailey CJ, Flatt PR; Antagonistic effects oftwo novel GIP analogues, (Hyp 3 )GIP and (Hyp 3 )GIPLys 16 PAL on the biological actions of GIP and longer term effectsin diabetic ob/ob mice; American Journal of Physiology Endocrinology and Metabolism, 292: E1674-1682, 2007Gault VA, Kerr BD, Irwin N, Flatt PR; C-terminal mini-PEGylation of glucose-dependent insulinotropic polypeptideexhibits metabolic stability and improved glucose homeostasis in dietary-induced diabetes; Biochemical Pharmacology,75: 2325-2333, 2008Irwin N, McClean PL, Hunter K, Gault VA & Flatt PR (Pro 3 )GIP[mPEG]: Novel long-acting mini-PEGylated gastricinhibitory polypeptide antagonist for obesity-diabetes therapy; British Journal of Pharmacology, 155: 690-701, 2008Irwin N, Hunter K, Flatt PR; Comparison of independent and combined chronic metabolic effects of GIP and CB 1receptor blockade in high-fat fed mice; Peptides, 29: 1036-1041, 200854

Irwin N, Hunter K, Frizzell N, Flatt PR; Antidiabetic effects of sub-chronic administration of the cannabinoid receptor(CB 1) antagonist, AM251, in obese diabetic (ob/ob) mice; European Journal of Pharmacology, 581: 226-233, 2008Irwin N, Cassidy RS, Flatt PR; Effects of Gastric Inhibitory Polypeptide (GIP) and related analogues on glucagon releaseat normo- and hyper-glycaemia in wistar rats and isolated islets; Biological Chemistry, 389: 189-193, 2008McClean PL, Gault VA, Irwin N, McCluskey JT and Flatt PR; Daily administration of the GIP-R antagonist (Pro 3 )GIP instreptozotocin-induced diabetes suggests insulin-dependent mechanisms are critical to anti-obesity-diabetes actionsof (Pro 3 )GIP; Diabetes Obesity and Metabolism, 10: 336-342, 2008Taylor A, Irwin N, McKillop AM, Flatt PR, Gault VA; Sub-chronic administration of 11beta-HSD1 inhibitor, carbenoxolone,improves glucose tolerance and insulin sensitivity in mice with diet-induced obesity; Biological Chemistry, 389:441-445, 2008Irwin N, McClean PL, Hunter K & Flatt PR; Metabolic effects of sustained activation of the GLP-1 receptor alone andin combination with background GIP receptor antagonism in high fat fed mice. Diabetes, Obesity and Metabolism(in press)Irwin N, Hunter K, Frizzell N & Flatt PR (2009) Antidiabetic effects of sub-chronic activation of the GIP receptoralone and in combination with background exendin-4 therapy in high fat fed mice. Regulatory Peptides (in press)55

8. MICROBIOLOGY AND BIOTECHNOLOGYRESEARCH GROUPRESEARCH STRATEGYThis Group concentrates on infectious diseases rather than degenerative diseases. Our focus is upon reaching adeeper understanding of the distribution, function and control of bacteria, protozoa and viruses of importance tobiomedical science; recognising the importance of the environment as a reservoir of microbial pathogens, and as asource of micro-organisms producing novel bioactive molecules. Analytical techniques have also been applied to otherbiological materials, which may be sources of molecules with therapeutic potential. As such ‘Infection free by design’is a theme that all the members of the group currently contribute to. This is a multidisciplinary approach, involvingclinicians, industry and academia, to solving problems associated with microbial infection in a public health context.The Group is currently actively involved in the following research projects:• Biology of Clostridium difficile whose associated disease (CDAD), within the ageing population, is a significantproblem to healthcare providers worldwide. It is essential that the incidence of this disease be contained notleast given the associated mortality rate of 6-15%.• Biology of the protozoan Cryptosporidium, an intracellular parasite responsible for many gastrointestinal infections,lately spectacularly so in Ireland.• Molecular methodologies for detecting and monitoring pathogens in novel environments, and for detecting lowcopy number genes associated with the metabolism of antiviral compounds.• A set of investigations of infective agents: viral pathogenesis and mechanism of antiviral drug resistance inBunyaviridae, arthropod-borne viruses that are important human pathogens, causing emerging infections inresponse to ecological changes.• The role of protease inhibitors in combination antiretroviral therapy, that have so substantially improved clinicaloutcome in HIV infection.• Interactions between viruses, the immune system and wound healing.• Proteomic techniques and tools for the analysis of micro-organisms of emerging medical and industrialimportance.• Advances in analytical science, particularly in mass spectrometry and NMR, that underpin the proteomiccapabilities.56

GROUP MEMBERSAcademic Staff:Professor Geoff McMullan, Group LeaderProfessor of MicrobiologyContact details:T: +44 (0)28 70324755g.mcmullan@ulster.ac.ukProfessor McMullan’s research continues to be focused upon the use of genomic information to provide a deeperunderstanding of how microorganisms function. In the past 10 years there has been a dramatic growth in theavailability of genetic data for microorganisms as a number of groups around the world have sequenced the genomesof over 500 organisms.These microorganisms include many disease-causing bacteria in addition to others exploited by the pharmaceuticaland biotechnology industries. By using this genetic information to understand how microorganisms function underdifferent conditions, such as evading the human immune system, it is possible to identify new drug targets or toidentify new products of commercial value.Professor McMullan and his team have developed a range of techniques to enable the exploitation of microbialgenomic information, including a platform of techniques to study the proteins expressed within a bacterial cell at agiven time. This work has involved collaboration with leading scientists at the University of Georgia at Athens (USA)and within the company, Applied Biosystems, a life science technology provider.This strategy has allowed us Professor McMullan and his team to identify cellular signaling mechanisms withina bacterium called Ochrobactrum anthropi, the cause of an increasing number of hospital acquired infections, thatcould allow this organism to resist ‘attack’ by macrophages used as part of the human response to infection (seeFigure below taken from Graham RL; Sharma MK; Ternan NG; Weatherly DB; Jackson PJ; Tarleton RL; McMullan G;A semi-quantitative GeLC-MS analysis of temporal proteome expression in the emerging nosocomial pathogenOchrobactrum anthropi.; Genome Biol.; 2007; 8, R110).57

Publications:Graham RJL, Graham C, McMullan G; Microbial proteomics: a mass spectrometry primer for biologists; Microbial CellFactories, 6:26, 2007Graham RLJ, Pollock CE, O’Loughlin SN, Ternan NG, Weatherly DB, Jackson PJ, Tarleton RL and McMullan G; (2007)Multidimensional analysis of the insoluble sub-proteome of Oceanobacillus iheyensis HTE831, an Alkaliphilic andhalotolerant deep-sea bacterium isolated from the Iheya ridge; Proteomics, 7: 82-91, 2007Graham RLJ, Sharma MK, Ternan NG, Weatherly DB, Tarleton RL, McMullan G; A Differential Semi-Quantitative GeLC-MS Analysis of Temporal Proteome Expression in the Emerging Nosocomial Pathogen Ochrobactrum anthropi. BMCGenome Biology; 8(6): R110, 2007Graham JE, Graham RLJ, Beirne R, McGilligan VE, Downes CS, Moore JE, Moore CBT, McMullan G; The use ofconjunctival swab for the proteomic characterisation of Dry Eye Syndrome; Journal of Proteomics and Bioinformatics;1: 20-33, 2008Professor Ibrahim BanatProfessor of MicrobiologyContact details:+44 (0)28 70323062im.banat@ulster.ac.ukMain research Interests:• Biosurfactants production and utilization in microbial cell adhesion, biofilm formation, pathogenicity, cellsignaling, enhanced oil recovery and bioremediation.• Exploring anticancer properties of selected fungi extract with the aim of developing novel anticancer drugs.• Molecular and cell biology and use of thermophilic geobacilli extremophilic bacteria and potential application.• Ethanol fermentation, isolation, characterization and optimization of fermentative alcohol producing yeasts andethanol production for use as biofuel.Professor Banat also aims to further develop exploring anticancer properties of fungi and identification of the activemolecules suitable for drug development.At present I also hold a lead a major industrial collaboration with Unilever, the University of Oxford and NewcastleUniversity, funded by the DTI, to examine routes for the production of sustainable consumer products based onthe microbial processing of agricultural feedstock and wastes. Specifically we aim to target the production ofbacterial biosurfactants as replacements for petrochemical surfactants. Such expertise is applicable to cosmetics andpharmaceutical Industries.Other key considerations relates to the use of appropriate agricultural feedstock which I hope to concentrate onis related to the use of microbial processes to develop sustainable systems, e.g. the production of biofuel ethanolfrom cellulosic wastes using simultaneous saccharification and fermentation at elevated temperatures and the areainvolving the exploitation of soil associated thermophilic extremophiles and their gene expression and potentialexploitation to effectively harness their unique properties.Esteem:• Invited keynote presentation in the StocExpo Turkey, the Black & Caspian Seas, Nov. 2008.• Was invited to act as an expert referee for research review for the University Professor of Microbiology ofKuwait 2008.58

Publications:Rodrigues L, Banat IM, Teixeira J, Oliveira R; Strategies for the prevention of microbiall biofilm formationon silicone rubber voice prostheses; Journal of Biomedical Materials Research Part B-Applied Biomaterials,81B: 358-370, 2007Marchant R, Franzetti A, Pavlostathis SG, Okutman Tas D, Erdbrűgger I, Űnyayar A, Mazmanci MA, Banat,IM; Thermophilic bacteria in cool temperate soils: are they metabolically active or continually added byglobal atmospheric transport; Applied Microbiology and Biotechnology, 5: 841-852, 2008Plessas S, Koliopoulos D, Kourkoutas Y, Psarianos C, Alexopoulos A, Marchant R, Banat IM and KoutinasAA; Upgrading of discarded oranges through fermentation using kefir in food industry; Food Chemistry,106, 40-49, 2008Plessas S; Bosnea L; Psarianos, Koutinas AA, Marchant R & Banat IM; Lactic acid production by mixed culturesof Kluyveromyces marxianus, Lactobacillus delbrueckii ssp bulgaricus and Lactobacillus helventicus; BioresourceTechnology 99: 5951-5955, 2008Thavasi R, Jayalakshmi S, Balasubramanian T and Banat IM; Production and characterization of a glycolipid biosurfactantfrom Bacillus megaterium using economically cheaper sources; World Journal of Microbiology and Biotechnology, 24: 917-925, 2008Wilkins MR, Mueller M, Eichling S and Banat IM; Fermentation of Xylose by the thermotolerant yeaststrains Kluyveromyces marxianus IMB2, IMB4, and IMB5 under anaerobic conditions; Process Biochemistry, 43:346-350, 2008Professor James DooleyProfessor of MicrobiologyContact details:T: +44 (0)28 70324427jsg.dooley@ulster.ac.ukProfessor James Dooley obtained a BSc in Microbiology from the National University of Ireland (Galway) in 1982and a PhD in Biochemistry from the University of Victoria (Canada) in 1988. He moved to the University of Ulsterin 1990 from the Moredun Research Institute in Edinburgh where he was undertaking research into improved diagnosticsof animal diseases.Professor Dooley’s current research interests are centred on developing a greater understanding of the biologyof human and animal pathogens. He has ongoing collaborations with the Northern Ireland Public Health serviceencouraging a service-based focus on some of the work. The main research areas are:• Improved molecular techniques for diagnostic microbiology and epidemiology, with a major focus on difficult toculture pathogens, particularly the protozoan parasite Cryptosporidium parvum.• Pathogenic mechanisms of Cryptosporidium species.• Role of protozoa in the ecology of pathogenic bacteria with particular emphasis on Campylobacter species.• Bacterial biofilm production by respiratory pathogens with emphasis on Pseudomonas aeruginosa.• Horizontal gene transfer in antibiotic resistant bacteria with particular emphasis on members of the genusEnterococcus.Professor Dooley’s work employs the latest molecular biology technology by embracing both proteomic and genomic59

analyses. However there is still a strong emphasis on understanding the whole organism and it’s relationship withthe environment. Therefore microscopy features prominently in many of the research activities. Molecular biologyhas been combined with the highly sensitive technique of Laser Capture Microscopy for improved diagnosis andmolecular epidemiology of a variety of pathogens that are difficult to culture.Professor Dooley has also been involved in a series of consultancy activities making use of the Innovation Voucherscheme operated by Invest Northern Ireland. Projects involving control of hospital acquired infection and point-ofcarediagnostics have been undertaken with industrial partners.Publications:Maeda Y, Kenny F, Coulter WA, Loughrey A, Nagano Y, Goldsmith CE, Millar BC, Dooley JS, Lowery CJ,Rooney PJ, Matsuda M, Moore JE; Bactericidal activity of denture-cleaning formulations against planktonichealth care-associated and community-associated methicillin-resistant Staphylococcus aureus; Am J InfectControl, 35: 619-622, 2007Nagano Y, Finn MB, Lowery CJ, Murphy T, Moriarty J, Power E, Toolan D, O’Loughlin A, Watabe M, McCorryKA, Crothers E, Dooley JS, Rao JR, Rooney PJ, Millar BC, Matsuda M, Elborn JS, Moore JE; Occurrence ofCryptosporidium parvum and bacterial pathogens in faecal material in the red fox (Vulpes vulpes) population,Vet Res Commun., 31: 559-564, 2007Shigematsu M, Nagano Y, Millar BC, Kenny F, Lowery CJ, Xiao L, Rao JR, Nicholson V, Watabe M, Heaney N, Sunnotel O,McCorry K, Rooney PJ, Snelling WJ, Dooley JSG, Elborn S, Matsuda M & Moore JE; Molecular detection and identificationof Cryptosporidium species in lettuce employing nested small subunit rRNA PCR and direct automated sequencing;British Journal of Biomedical Science, 64:133-135, 2007Sunnotel O, Snelling WJ, McDonough N, Browne L, Moore JE, Dooley JS, Lowery CJ; Effectiveness of standardUV depuration at inactivating Cryptosporidium parvum recovered from spiked Pacific oysters (Crassostreagigas); Appl Environ Microbiol, 73: 5083-5087, 2007Maeda Y, Loughrey A, Earle JA, Millar BC, Rao JR, Kearns A, McConville O, Goldsmith CE, Rooney PJ, DooleyJS, Lowery CJ, Snelling WJ, McMahon A, McDowell D, Moore JE; Antibacterial activity of honey againstcommunity-associated methicillin-resistant Staphylococcus aureus (CA-MRSA); Complement Ther Clin Pract.14: 77-82, 2008Snelling WJ, Stern NJ, Lowery CJ, Moore JE, Gibbons E, Baker C, Dooley JS; Colonization of broilers byCampylobacter jejuni internalized within Acanthamoeba castellanii; Arch Microbiol, 189: 175-179, 2008Stirling J, Griffith M, Dooley JS, Goldsmith CE, Loughrey A, Lowery CJ, McClurg R, McCorry K, McDowell D, McMahonA, Millar BC, Rao J, Rooney PJ, Snelling WJ, Matsuda M, Moore JE; Zoonoses Associated with Petting Farms and OpenZoos; Vector Borne Zoonotic Diseases, 8: 85-92, 2008Stirling J, Griffith M, Blair I, Cormican M, Dooley JS, Goldsmith CE, Glover SG, Loughrey A, Lowery CJ, Matsuda M,McClurg R, McCorry K, McDowell D, McMahon A, Cherie Millar B, Nagano Y, Rao JR, Rooney PJ, Smyth M, SnellingWJ, Xu J, Moore JE; Prevalence of gastrointestinal bacterial pathogens in a population of zoo animals; Zoonoses PublicHealth, 55:166-172, 200860

Professor Roger MarchantMain Research Interests:• Global transport of bacteria and their survival under adverse conditions.• Production of biosurfactants by microorganisms.• Thermophilic soil bacteria of the genus Geobacillus and their potential use for the bioremediation of hydrocarboncontaminated sites.• Ethanol fermentation systems for the production of potable and fuel alcohol.• The use of lignocellulosic biomass as a feedstock for the production of bioethanol.During the period from August 2007 to July 2008 the major funded research activities being undertaken were theDTI funded project in collaboration with the University of Oxford, University of Newcastle and Unilever Ltd. onthe sustainable production of biosurfactants to replace chemical surfactants in domestic products; the recycling ofwastes from potato processing industries for the production of bioethanol. The latter project was funded by theBritish Council and was a collaborative project with the National Technical University of Athens and the NationalAgricultural Research Foundation of Greece. Research supervision for the period covered 5 students one of whomsuccessfully completed during the period. Papers were also presented at a meeting on Protection and Restorationof the Environment 29 June-3 July 2008 held in Kefallonia Greece.Major measures of esteem during this period were an invitation to give a lecture at the University of Mersin in Turkey(27 May 2008), appointment as an Executive editor of the international journal Biotechnology Letters, the award ofan honorary doctorate from the University of Patras in Greece (December 2007) and the award of a Senior DistinguishedResearch Fellowship by the University of Ulster (December 2008). Council membership for the BritishMycological Society was also extant during this period.Professor Marchant delivering a lecture entitledΌλα είναι παντού, το περιβάλλον επιλέγει(“Everything is everywhere, the environment selects”)during the honorary degree ceremony in the University of Patras.Despite reaching normal retirement age in July 2008, Professor Marchant hopes to continue research activities andfuture research plans involve a focus on the production of bioethanol from lignocellulosic biomass and continuinginvestigation of the global distribution and transport of thermophilic bacteria.Publications:Dimitrellou D, Kourkoutas Y, Banat IM, Marchant R and Koutinas AA; Whey-cheese production using freezedriedkefir culture as a starter; Journal of Applied Microbiology, 103, 1170-1183, 2007Dritsa V, Rigas F, Natsis K and Marchant R; Characterization of a fungal strain isolated from a polyphenolpolluted site; Bioresource Technology, 98: 1741-1747, 2007Perfumo A, Banat IM, Marchant R and Vezzulli L; Thermally enhanced approaches for bioremediation ofhydrocarbon-contaminated soils; Chemosphere, 66: 179-184, 200761

Plessas S, Bekatorou A, Koutinas AA, Soupioni M, Banat IM and Marchant R; Use of Saccharomyces cerevisiaecells immobilized on orange peel as biocatalyst for alcoholic fermentation; Bioresource Technology, 98: 860-865, 2007Plessas S, Bekatorou A, Kanellaki M, Koutinas AA, Marchant R and Banat IM; Use of immobilized cell biocatalysts inbaking; Process Biochemistry, 42: 1244-1249, 2007Marchant R, Franzetti A, Pavlostathis SG, Okutman Tas D, Erdbrűgger I, Űnyayar A, Mazmanci MA, Banat IM;Thermophilic bacteria in cool temperate soils: are they metabolically active or continually added by globalatmospheric transport; Applied Microbiology and Biotechnology, 5: 841-852, 2008Plessas S, Koliopoulos D, Kourkoutas Y, Psarianos C, Alexopoulos A, Marchant R, Banat IM and Koutinas AA;Upgrading of discarded oranges through fermentation using kefir in food industry; Food Chemistry, 106, 40-49, 2008Plessas S; Bosnea L; Psarianos, Koutinas AA, Marchant R & Banat IM; Lactic acid production by mixed culturesof Kluyveromyces marxianus, Lactobacillus delbrueckii ssp bulgaricus and Lactobacillus helventicus; BioresourceTechnology 99: 5951-5955, 2008Professor W. Franklin SmythProfessor of Bio-Analytical ChemistryContact details:T: +44 (0)28 70324425wf.smyth@ulster.ac.ukProfessor Franklin Smyth is Professor of Bioanalytical Chemistry whose research interests lie in the general area ofidentification and determination of low molecular mass organic molecules of biological importance, such as naturalproducts in plants and synthetic drugs in biological matrices.Professor Smyth’s main research interests are:(a)(b)metabolomic investigations of natural products, biological activity-testing and structural characterisation of plantsubstances with potential medicinal significance, particularly those that have antibacterial potential; anddevelopment of mass spectrometric assays for psycho-active drugs in hair and saliva samples.Franklin is using LC-ESI-ion trap mass spectrometry and LC-ESI-QToF mass spectrometry in metabolomicinvestigations of natural products and the development of mass spectrometric assays for psycho-active drugs.62

He has developed a research link with Dr Peter Brooks (University of The Sunshine Coast, Queensland, Australia) toinvestigate the isolation and characterisation of local natural product pharmaceuticals, from which technology transfercould arise in the discovery of a new anti-MRSA antibacterial, for example. Bioassay-led separation of the activecrude fractions is currently being refined using LC-ESI-MS to lead to the characterisation of individual compoundswith antibacterial activity.Suicide in Northern Ireland is the highest in the UK and it has been suggested that selective serotonin reuptakeinhibitors, which are the most widely used antidepressant drugs, are associated with an increased risk of suicidalbehaviour and self-harm. Professor Smyth, Dr Stephen McClean, Dr Bernie Doherty, Dr Virginia Rodriguez, togetherwith Professor Julian Leslie in Psychology, have developed a technique based on LC-ESI-MS that can detect earlieranti-depressant and other drug use in hair samples. It is intended that this will be used in a pilot study using hairsamples from at-risk young people in North and West Belfast. This will ultimately allow for an investigation into thepossible association between self-harm/suicide and such drugs in these regions.PublicationsDoherty B, O’Donnell F, Smyth WF, Leslie JC, Ramachandran VN, Boyd NS, Hack CJ, O’Kane E and McClean S; A studyof the analytical behaviour of selected psycho-active drugs using liquid chromatography, ion trap mass spectrometry,gas chromatography and polarography and the construction of an appropriate database for drug characterisation;Talanta, 72: 755–761, 2007Doherty B, Rodriguez V, Leslie JC, McClean S and Smyth WF; An ESI- MS/MS investigation of selected psychoactivepharmaceuticals and its application in drug and metabolite profiling by LC-ESI-MS/MS; Rapid Communications in MassSpectrometry, 21: 2031-2038, 2007Smyth WF and Rodriguez V; Recent studies of the electrospray ionisation behaviour of selected drugs and theirapplication in capillary electrophoresis mass spectrometry and liquid chromatography-mass spectrometry; Journal ofChromatography A, 1159: 159-174, 2007Smyth TJ, Ramachandran VN, McGuigan A, Hopps J and Smyth WF; The Characterisation of Nicotine and RelatedCompounds using Electrospray Ionisation with Ion Trap Mass Spectrometry and with Quadrupole Time of Flight MassSpectrometry and their detection by LC-ESI-MS; Rapid Communications in Mass Spectrometry, 21: 557-566, 2007Dr Anne BridgenLecturer in BioimagingContact details:T: +44 (0)28 70324903a.bridgen@ulster.ac.ukDr Bridgen’s research focuses on the molecular biology of a group of exotic viruses, the Bunyaviridae, some of whichare severe pathogens of man and animals. They are negative sense, tri-segmented RNA viruses that are carried by avariety of (mainly) arthropod vectors, particularly ticks and mosquitoes. Her research focuses on three main areas:Pathogenesis of the diseaseDr Bridgen has studied the effects on wild type and immune deficient mice infected with a relatively apathogenicvirus, Dugbe virus in collaboration with Professor John Fazakerley in Edinburgh funded by the Royal Society. Annecontinues to work on a research project in collaboration with Dr Michael Baron of the Institute of Animal Health inPirbright (IAH) with funding awarded by the BBSRC to study one of the serious pathogens in this virus group, Nairobisheep disease virus, using the special containment facilities available at the IAH.63

Biochemical studies/ viral evasion of innate immunityDr Bridgen is particularly interested in a novel domain seen in one of the nairoviral proteins, the polymerase protein,which has recently been shown to remove both ubiquitin and the ubiquitin-like molecule ISG-15 from targetedproteins (see Frias-Staheli N et al below). It seems that this is a new way in which the virus can evade the host’simmune defence mechanisms. This paper is of major significance becasue it elucidated details of a novel way in whichviruses evade the innate immune response, by modifying the extent of the ubiquitin like protein ISG15 bound tocellular proteins. I continued to research in this area (along with a Masters student) in efforts to identify cellularinteraction partners of this viral protease.Viral reverse geneticsThis is the manipulation of viral cDNA in order to modify the virus, which is the best way to study the role of specificproteins and gene regulatory regions.Dr Bridgen is a member of the Editorial Board of the Journal of General Virology.Publications:Frias-Staheli N, Giannakopoulos NV, Kikkert M, Taylor SL, Bridgen A, Paragas J, Richt JA, Rowland RR, SchmaljohnCS, Lenschow DJ, Snijder EJ, García-Sastre A, Virgin HW 4 th ; Ovarian tumor domain-containing viral proteases evadeubiquitin- and ISG15-dependent innate immune responses; Cell Host Microbe, 2: 404-416, 2007Dr Colm LoweryLecturer in Medical MicrobiologyContact details:T: +44 (0)28 70323528cj.lowery@ulster.ac.ukMain research interests:Dr Colm Lowery’s main research interest is in the development of rapid molecular techniques for diagnostic microbiologyand epidemiology, with a major focus on difficult to culture pathogens, particularly the protozoan parasiteCryptosporidium parvum.In order to understand the disease process and alleviate symptoms of disease we need to study its ‘little known’pathogenesis. Colm is extremely interested in researching the pathogenic mechanisms of Cryptosporidium speciesand has recently published an important investigative paper in this field in Molecular and Cellular Proteomics (see detailsunder “publications” below).Recently Colm has been investigating the application of a variety of technologies including Laser Capture Microscopyand real time detection systems for improved diagnosis and molecular epidemiology of a variety of difficult to culturebacteria and protozoan pathogens of medical importance. He has recently published a research paper using thistechnology to detect single cells of Cryptosporidum sp. on archive glass slides in the Journal of Clinical Microbiology (seedetails under “publications” below).This work has also formed the basis of several recent successful funding applications including a Northern IrelandWater sponsored PhD studentship (£8,000 for five years). Other successful funding applications in this area ofresearch include: Office of Innovation: £750 towards consumable costs for investigating the use of laser capturemicro-dissection (LCM) in detecting of Cryptosporidium oocysts from archive glass slides; Pre-Proof of Concept(POC) project TD Ref No: 135, £6750 awarded for investigating the development of a Laser Capture CryptosporidiumGenotyping Service for Water Managers.Potential end users for this rapid detection and genotyping service – as determined by extensive marketing analysisby students at UU Jordanstown - are NI/UK water managers. Drinking water managers are obligated to supply water64

for domestic use or food production and so must comply with the standards in the (UK) Northern Ireland WaterQuality Regulations, which incorporate European Union standards and more stringent UK national standards.Dr Lowery is currently co-supervising three MSc students with Professor James Dooley and Dr Olaf Sunnotel – theaim of the work being to develop a rapid diagnostic test for Mycobacterium tuberculosis. This work is being carriedout in conjunction with Professor John E. Moore and Dr BC Millar at Belfast City HospitalIn addition to this work Colm also has an interest in researching the epidemiology of Cryptosporidium sp. in theenvironment and has recently published papers in this area (see below):Publications:Maeda Y, Kenny F, Coulter WA, Loughrey A, Nagano Y, Goldsmith CE, Millar BC, Dooley JS, Lowery CJ,Rooney PJ, Matsuda M, Moore JE; Bactericidal activity of denture-cleaning formulations against planktonichealth care-associated and community-associated methicillin-resistant Staphylococcus aureus; Am J InfectControl, 35: 619-622, 2007Nagano Y, Finn MB, Lowery CJ, Murphy T, Moriarty J, Power E, Toolan D, O’Loughlin A, Watabe M, McCorryKA, Crothers E, Dooley JS, Rao JR, Rooney PJ, Millar BC, Matsuda M, Elborn JS, Moore JE; Occurrence ofCryptosporidium parvum and bacterial pathogens in faecal material in the red fox (Vulpes vulpes) population,Vet Res Commun., 31: 559-564, 2007Sunnotel O, Snelling WJ, McDonough N, Browne L, Moore JE, Dooley JS, Lowery CJ; Effectiveness of standardUV depuration at inactivating Cryptosporidium parvum recovered from spiked Pacific oysters (Crassostreagigas); Appl Environ Microbiol, 73: 5083-5087, 2007Shigematsu M, Nagano Y, Millar BC, Kenny F, Lowery CJ, Xiao L, Rao JR, Nicholson V, Watabe M, Heaney N, Sunnotel O,McCorry K, Rooney PJ, Snelling WJ, Dooley JSG, Elborn S, Matsuda M & Moore JE; Molecular detection and identificationof Cryptosporidium species in lettuce employing nested small subunit rRNA PCR and direct automated sequencing;British Journal of Biomedical Science, 64:133-135, 2007Maeda Y, Loughrey A, Earle JA, Millar BC, Rao JR, Kearns A, McConville O, Goldsmith CE, Rooney PJ, DooleyJS, Lowery CJ, Snelling WJ, McMahon A, McDowell D, Moore JE; Antibacterial activity of honey againstcommunity-associated methicillin-resistant Staphylococcus aureus (CA-MRSA); Complement Ther Clin Pract.14: 77-82, 2008Snelling WJ, Stern NJ, Lowery CJ, Moore JE, Gibbons E, Baker C, Dooley JS; Colonization of broilers byCampylobacter jejuni internalized within Acanthamoeba castellanii; Arch Microbiol, 189: 175-179, 2008Stirling J, Griffith M, Dooley JS, Goldsmith CE, Loughrey A, Lowery CJ, McClurg R, McCorry K, McDowell D, McMahonA, Millar BC, Rao J, Rooney PJ, Snelling WJ, Matsuda M, Moore JE; Zoonoses Associated with Petting Farms and OpenZoos; Vector Borne Zoonotic Diseases, 8: 85-92, 2008Stirling J, Griffith M, Blair I, Cormican M, Dooley JS, Goldsmith CE, Glover SG, Loughrey A, Lowery CJ, Matsuda M,McClurg R, McCorry K, McDowell D, McMahon A, Cherie Millar B, Nagano Y, Rao JR, Rooney PJ, Smyth M, SnellingWJ, Xu J, Moore JE; Prevalence of gastrointestinal bacterial pathogens in a population of zoo animals; Zoonoses PublicHealth, 55:166-172, 200865

Dr Stephen McCleanLecturer in ProteomicsContact details:T: +44 (0)28 70324406s.mcclean@ulster.ac.ukBrief profile:Dr Stephen McClean obtained undergraduate, Masters and PhD degrees from the University of Ulster and held aresearch position there before becoming a Lecturer in Proteomics in December 2001.Main research interests:As an analytical chemist he has broad interest in the application of chromatography and mass spectrometrictechnologies to the analysis of a range of molecules in biological matrices.Of particular interest is the application of ion trap, MALDI-TOF and QToF MS/MS to the isolation and characterizationof novel peptides from amphibian skin secretions, in particular those from the tiger leg monkey frog Phyllomedusahypochondrialis azurea. The characterization and bioactivity testing of molecules from other amphibian skin secretions,reptile and arachnid venoms also fall within the remit of this research. QTOF MS/MS de novo peptide sequencing hasbeen successfully applied to the determination of novel peptide structures in these matrices.A T_ PHY P_ NEW _ 1 8 0 _ 7 2 _ 1 0 0 8 0 8 _ 1 5 8 9 Ma x En t 3 9 3 [Ev - 3 7 2 5 4 ,It5 0 ,En 1 ] ( 0 .0 5 0 ,2 0 0 .0 0 ,0 .2 0 0 ,1 4 0 0 .0 0 ,2 ,C mp ) 1 : TO F MS MS 7 9 5 .5 0 ES +1 0 0L G P A L I TR K P L K G K P b Ma xPK G K L PK R T I L A P G L y Ma x1 4 7 3 .9 9b 1 41 5 8 9 .0 6 ( M +H ) +%01 2 8 8 .9 1b 1 27 3 7 .5 73 1 4 .2 3 4 2 4 .3 01 4 7 5 .0 91 0 4 7 .7 96 5 2 .4 9 7 9 5 .1 2 9 0 9 .6 21 8 6 .1 3a 51 1 7 5 .8 11 3 6 0 .8 51 0 2 2 .7 1 b 1 01 5 8 9 .9 11 5 8 .9 46 4 4 .9 1M/z1 0 0 2 0 0 3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0 9 0 0 1 0 0 0 1 1 0 0 1 2 0 0 1 3 0 0 1 4 0 0 1 5 0 0 1 6 0 0He has also studied the profiling of anti-depressent and anti-psychotic agents in human hair samples using ion trapmultiple stage mass spectrometry compared with QToF MS/MS to elucidate fragmentation pathways for selecteddrugs and metabolites.Esteem indicators:Stephen has over 40 peer-reviewed publications and has secured income for his research as well as undertakinganalytical consultancy work with external companies. To date he has supervised eight PhD projects to completionand is currently supervising research projects at undergraduate and postgraduate level. He is a member of theOrganising Committee of the Irish Mass Spectrometry Society, the British Mass Spectrometry Society and the RoyalSociety of Chemistry. He is also a Member of the Editorial Board of the Open Spectroscopy Journal and acts asreviewer for the following journals: Analytica Chimica Acta, Electrophoresis, Journal of Comparative Biochemistryand Physiology, Proteomics and Rapid Communications in Mass Spectrometry.During the year Stephen was invited to deliver a presentation entitled: “QTOF MS/MS de novo sequencing of naturallyoccurring peptides” at the Irish Mass Spectrometry Society Proteomics Meeting, Food Research Centre, Ashtown,66

Dublin (in November 2007) and he was also Chair of the afternoon session of Irish Mass Spectrometry SocietyConference, in Dublin (May 2008).Publication:Thompson AH, Bjourson AJ, Orr DF, Shaw C and McClean S; Amphibian skin secretomics: application of parallelquadrupole time-of-flight mass spectrometry and peptide precursor cDNA cloning to rapidly characterize the skinsecretory peptidome of Phyllomedusa hypochondrialis azurea: discovery of a novel peptide family, the hyposins;Journal of Proteome Research, 6: 3604 –3613, 2007Dr Poonam Singh (nee Nigam)Senior Lecturer in BiotechnologyContact details:T: +44 (0)28 70324053p.singh@ulster.ac.ukIndicators of esteemDr Singh (nee Nigam) is currently an Associate Advisor in the Biotechnology British Council. She is also acted asan External Examiner PhD student viva at Manchester University (Ms Castelo sponsored by European CommissionMarie Curie Fellowship for early stage Research Training Program).Dr Singh was invited to give the following lectures at international conferences:“Bioremediation of Textile waste water through solid state fermentation systems”, at the International Conference on NewHorizons in Biotechnology Trivandrum, India (26-29 November 2007 – IL, 26: 047, 2007).“Studies on Encapsulated and entrapped yeast for Bioethanol production”, Biospectrum, International Symposium onAdvances in Food Biotechnology & Nutrition, (30 Nov-1 Dec 2007), Mar Athanasios College for Advanced Studies,Tiruvalla, Kerala, India (pp. 25-26: LL-06, 2007).Publications:Genest S, Kerr C, Shah A, Rahman MM, Naser GMM, Nigam P, Nahar L, Sarker SD; Comparative Bioactivity Studies onTwo Mimosa Species; The Latin American And Caribbean Bulletin of Medicinal And Aromatic Plants (BLACPMA Derechos dePublicación © 2008 Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas, 7: 38–43, 2008Robinson T & Nigam P; Remediation of textile dye-waste water using a white rot fungus Bjerkandera adusta throughsolid-state fermentation (SSF); Applied Biochemistry and Biotechnology, 151: 618-628, 2008Dr Nigel TernanLecturer in Microbial ProteomicsContact details:T: +44 (0)28 70323063ng.ternan@ulster.ac.ukDr Nigel Ternan gained his Ph.D. from Queen’s University Belfast (1997) and was apointed to a lectureship inMicrobiology at the University of Ulster in 2003, having previously held the position of Research Fellow at UU.He has previously investigated the catalytic activities of novel microbial enzymes from the point of view of both67

environmental remediation and as routes to new bioproducts. Recent biomedical sciences research in the Ternanlaboratory has focused on a systems biology approach to understanding stress response in the important humanpathogen, Clostridium difficile, as well as the development of nanostructured coatings to prevent biofouling of medicaldevices and collaboration with local industry to develop in situ treatment processes for reducing infective load inhealthcare environments.The completion of successful programmes of research by Dr Ternan has resulted in over 20 peer-reviewed publicationsand competitively awarded external funding in excess of £60k. The Ternan laboratory has recently characterised abiological pathway leading to the production of the antiviral compound, phosphonoacetate Analysis of this pathwaywas initially facilitated by funding from the Royal Society and a subsequent 2 year grant from the prestigious UKEngineering and Physical Sciences Research Council has enabled the Ternan laboratory to undertake a systemsbiology investigation of the pathway in collaboration with the School of Mechanical and Aerospace Engineering atQUB.Clostridium difficile has risen from relative obscurity 20 years ago to be recognised as an important hospital pathogen,responsible for a wide spectrum of enteric diseases. Limited post-genomic information currently exists on C. difficile.Therefore, a comprehensive post-genomic analysis of clinically relevant stress in C. difficile is underway in the Ternanlaboratory, which utilises proteomics, transcriptomics and biochemical analyses to further our understanding ofhow this pathogen works at a systems level. The work is driven in part by in silico analyses of potential drug targetsidentified in comparative studies followed by expression studies to determine the regulation of these virulencefactors. This work should lead to greater understanding of their physiological role, and thus allow the developmentof strategies to disrupt or interfere with that role, thereby weakening the pathogen. Overall the work should allowus to elevate our understanding of genome function in this important pathogen.The Ternan laboratory also delivers consultancy services for industrial partners. Recent clients include SeagateTechnologies, Invista Chemicals, Ltd., and Soltex Global Ltd. All these companies have benefited from the expertiseavailable within the Microbiology and Biotechnology Research Group and the Ternan laboratory.Dr Ternan currently supervises two PhD students and six MSc students and has previously supervised five MResstudents. He has acted as an expert reviewer for: Proteomics, Journal of Proteome Research, Journal of Bacteriology,Can. Journal of Microbiology, Water Research, Environmental Technology, Biodegradation, and also on three occasionsfor the Biotechnology and Biological Sciences Research Council. He is a member of the Society for GeneralMicrobiology, serving on the Irish Branch Committee from 1998-2001, holds a 1 st Dan black belt in Shotokan Karate,and has won gold in several international Karate competitions.In the period under review, Dr Ternan (along with Professor McMullan) provided consultancy services for InvistaTextiles, Londonderry, providing a “Report on wastewater treatment plant considerations to increase efficiency”. He68

also secured a Vacation Studentship from the Society for General Microbiology for a project entitled: “Realisation ofthe extracellular proteome of Clostridium difficile strain 630 using a novel biotinylation-driven enrichment strategy”.Publications:Graham RLJ, Sharma MK, Ternan NG, Weatherly DB, Tarleton RL, McMullan G; A Differential Semi-Quantitative GeLC-MS Analysis of Temporal Proteome Expression in the Emerging Nosocomial Pathogen Ochrobactrum anthropi. BMCGenome Biology (in press)Graham RLJ, Pollock CE, O’Loughlin SN, Ternan NG, Weatherly DB, Jackson PJ, Tarleton RL and McMullan G; (2007)Multidimensional analysis of the insoluble sub-proteome of Oceanobacillus iheyensis HTE831, an Alkaliphilic andhalotolerant deep-sea bacterium isolated from the Iheya ridge; Proteomics, 7: 82-91, 200769

9. NORTHERN IRELAND CENTRE FOR FOODAND HEALTH (NICHE)Human nutrition research at the University of Ulster is centred in the Northern Ireland Centre for Food & Health(NICHE), a centre of excellence set up with EU structural funds in 1996 to provide greater understanding of dietrelatedhealth issues. NICHE has 20 academic, 5 technical and 9 research staff, as well as 29 postgraduate researchstudents.Research is aimed at identifying food components or dietary regimes likely to lead to benefits for human health.An important aspect of our work is the development and validation of biomarkers for chronic disease to facilitatedietary intervention studies in healthy subjects at risk of disease.Human Nutrition research within NICHE was recently reviewed and reorganized under the following six researchheadings:• energy balance, appetite regulation and nutrition education;• folate and related B vitamins in health and disease;• phytochemicals and gut microflora in health and disease;• micronutrient modulation of immune and inflammatory responses;• nutrition toxicology and child development; and• psychological factors associated with food and nutrition.Research remains focused on human dietary interventions around the core research facility of the human interventionstudies unit. Although much of our research effort is focussed on studies in healthy humans, in recent years we haveextended our efforts to include research in specific patient groups through establishing collaborations with cliniciansin the specialised areas of cardiology, gastroenterology and paediatrics. Some, though not all, of this work includesmore dietetics related research, which is expected to have greater emphasis within NICHE in the longer term.Images of some of the facilities available in the Human Intervention Studies Unit (HISU),within the Centre for Molecular Biosciences, University of Ulster70

Other core research facilities identified were those involved with the analysis of water-soluble vitamins, fattyacids and fat-soluble vitamins, trace elements and immune measures. Most other analysis would be outsourced tointernational centres of excellence including the Vitamin Research Laboratory, Trinity College Dublin and the MRCHuman Nutrition Research, Cambridge. Research funding opportunities will be mainly through a reactionary modeand opportunities will include the recent MRC’s Patient Research Cohorts Initiative Call. Proactive approaches willbe focused under the research areas identified above.In most cases it is anticipated that research outcomes will be of direct relevance to public health but fundamentalresearch in vitro and in collaboration with those undertaking genomic and proteomic research will remain a feature.In particular, the University’s investment in a metabolomics facility under SRIF 3 will give exciting opportunities forbasic research in humans. Researchers within NICHE will continue to engage with the food industry in an effort toexploit potentially lucrative opportunities in relation to the functional food business and the health claims agenda. Itis anticipated that part of this portfolio of research will be applied research of direct relevance to the food industrywith consultancy encouraged and providing a stronger stance on intellectual property and commercialisation thanhitherto.MEMBERS OF THE GROUP:Professor Sean StrainProfessor of Human NutritionDirector of NICHEContact Details:T: +44 (0)28 70324795jj.strain@ulster.ac.ukAfter graduating with a BSc (Chemistry), BAgr (Agricultural Chemistry) and PhD (Nutritional Biochemistry), all fromQueen’s University, Professor Sean Strain spent several years (1977-1980) in academia in Australia before joining theUniversity of Ulster 1981. He is Professor of Human Nutrition (since 1994) in the Northern Ireland Centre for Food& Health (NICHE). His research interests are mainly in the areas of nutrition and toxicology, trace element nutritionand in B-vitamin and homocysteine metabolism. The work on nutrition and toxicology involves collaboration withUniversity of Rochester, New York and the Ministry of Health, Seychelles in a longitudinal observational motherchildcohort which is investigating associations between maternal exposure to nutrients, especially long-chainpolyunsaturated fatty acids (LCPUFA) and child development in the Republic of Seychelles where fish consumptionis high. Findings to date, support the potential importance to child development of n-3 LCPUFA present in fish andof LCPUFA in the overall diet and indicate that the beneficial effects of LCPUFA can outweigh the adverse effects ofmaternal methyl-mercury exposure. Work on B-vitamins and homocysteine metabolism is in collaboration with thegroup led by Professor Helene McNulty.Professor Strain is a member of various national and international committees including the Dietetic Products andNutrition Panel of the European Food Safety Authority, Parma and Chairs its Working Group on Health Claims;Food Strategy Implementation Partnership; MRC College of Experts; MRC Physiological Systems and Clinical SciencesSpecial Review Panel; Food Safety Promotions Board, Cork; Member of the Board of Directors, International LifeSciences Institute, Europe; Member of the Board of Governors of BBSRC Food Research Institute, Norwich;Chairman of the Board of European Nutrition Leadership Programme.Invited Lectures9-13 June 2008: EURECCA Annual Meeting, Montenegro5 June 2008: Health Claims Meeting, Health & Wellbeing, Special Interest Group, London13-15 May 2008: Second International Seafood & health Meeting, Bergen25-29 March 2008: Organised Workshop and gave opening talk, PHIME Meeting, Prague5 March 2008: Chair, Dairy Council Conference, Belfast8 November 2007: Colloquium on Nutrient Profiling, FIN, Paris71

26-28 Sept 2007: International Seafood Congress, Dublin29-31 Aug 2007: SSA GutImpact Conference, Haikko - ‘From research to products’Publications:Barnes MS, Bonham MP, Robson PJ, Strain JJ, Lowe-Strong AS, Eaton-Evans J, Ginty F and Wallace JMW; Assessmentof 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D3 concentrations in male and female multiple sclerosis patientsand control volunteers, Multiple Sclerosis, 13: 670-672, 2007Harvey LJ, Dainty JR, Hollands WJ, Bull VJ, Hoogewerff JA, Foxall RJ, McAnena L, Strain JJ and Fairweather-Tait SJ; Effectof high-dose iron supplements on fractional zinc absorption and status in pregnant women, American Journal ofClinical Nutrition, 85: 131-136, 2007Hodkinson CF, Kelly M, Alexander HD, Bradbury I, Robson PJ, Bonham, MP, O’Connor JM, Coudray C, Strain JJ andWallace JMW; Effect of zinc supplementation on the immune status of healthy older individuals aged 55 - 70 years:the ZENITH study, Journal of Gerontology: Biological Sciences, 62A, 6: 598-608, 2007Hoey L, McNulty H, Askin N, Dunne A, Ward M, Pentieva K, Strain JJ, Molloy AM, Flynn C, Scott JM. Impact of avoluntary food fortification policy on folate, related B-vitamin status and homocysteine in healthy adults, AmericanJournal of Clinical Nutrition, 86: 1405-1413, 2007Myers GJ, Davidson PW, Strain JJ; Nutrient and methyl mercury exposure from consuming fish, Journal of Nutrition,137: 2805-2808, 2007Stewart-Knox BJ, Simpson EEA, Parr H, Rae G, Polito A, Intorre F, Meunier M, Andriollo M, O’Connor JM, Coudray C,Strain JJ; Taste acuity in response to zinc in older Europeans, British Journal of Nutrition, 99: 129-136, 2007Bonham MP, Duffy EM, Robson PJ, Wallace JM, Myers GJ, Davidson PW, Clarkson TW, Shamlaye CF, Strain JJ, LivingstoneMB; Contribution of fish to intakes of micronutrients important for fetal development: a dietary survey of pregnantwomen in the Republic of Seychelles, Public Health Nutrition, 6: 1-9, 2008Bonham MP, Duffy EM, Wallace JM, Robson PJ, Myers GJ, Davidson PW, Clarkson TW, Shamlaye CF, Strain JJ; Habitual fishconsumption does not prevent a decrease in LCPUFA status in pregnant women (the Seychelles Child DevelopmentNutrition Study), Prostaglandins Leukot Essent Fatty Acids, 78: 343-350, 2008Cashman KD, Hill TR, Lucey AJ, Taylor N, Seamans KM, Muldowney S, Fitzgerald AP, Flynn A, Barnes MS, Horigan G,Bonham MP, Duffy EM, Strain J, Wallace JM, Kiely M; Estimation of the dietary requirement for vitamin D in healthyadults, American Journal of Clinical Nutrition, 88: 1535-1542, 2008Cashman KD, Hill TR, Cotter AA, Boreham CA, Dubitzky W, Murray L, Strain J, Flynn A, Robson PJ, Wallace JM, Kiely M;Low vitamin D status adversely affects bone health parameters in adolescents, American Journal of Clinical Nutrition,87: 1039-1044, 2008Choi SW, Benzie IF, Ma SW, Strain JJ, Hannigan BM; Acute hyperglycemia and oxidative stress: direct cause and effect?,Free Radic Biol Med, 44: 1217-1231, 2008Davidson PW, Strain JJ, Myers GJ, Thurston SW, Bonham MP, Shamlaye CF, Stokes-Riner A, Wallace JM, Robson PJ,Duffy EM, Georger LA, Sloane-Reeves J, Cernichiari E, Canfield RL, Cox C, Huang LS, Janciuras J, Clarkson TW;Neurodevelopmental effects of maternal nutritional status and exposure to methylmercury from eating fish duringpregnancy, Neurotoxicology, 29: 767-775, 2008Hill TR, Cotter AA, Mitchell S, Boreham CA, Dubitzky W, Murray L, Strain JJ, Flynn A, Robson PJ, Wallace JM, Kiely M,Cashman KD; Vitamin D status and its determinants in adolescents from the Northern Ireland Young Hearts 2000cohort, British Journal of Nutrition, 99: 1061-1067, 2008Hoey L, McNulty H, Askin N, Dunne A, Ward M, Pentieva K, Strain J, Molloy AM, Flynn CA, Scott JM, Effect of a72

voluntary food fortification policy on folate, related B vitamin status, and homocysteine in healthy adults, AmericanJournal of Clinical Nutrition, 86: 1405-1413, 2008Simpson EE, McConville C, Rae G, O’Connor JM, Stewart-Knox BJ, Coudray C, Strain JJ; Salivary cortisol, stress andmood in healthy older adults: the Zenith study, Biol Psychol, 78: 1, 1-9, 2008Stanisławska-Sachadyn A, Brown KS, Mitchell LE, Woodside JV, Young IS, Scott JM, Murray L, Boreham CA, McNulty H,Strain JJ, Whitehead AS; An insertion/deletion polymorphism of the dihydrofolate reductase (DHFR) gene is associatedwith serum and red blood cell folate concentrations in women, Human Genetics, 123: 289-295, 2008Stanisławska-Sachadyn A, Woodside JV, Brown KS, Young IS, Murray L, McNulty H, Strain JJ, Boreham CA, ScottJM, Whitehead AS, Mitchell LE; Evidence for sex differences in the determinants of homocysteine concentrations,Molecular Gen Metab, 93: 355-362, 2008Stewart-Knox BJ, Bunting BP, Gilpin S, Parr HJ, Pinhão S, Strain JJ, de Almeida MD, Gibney M; Attitudes toward genetictesting and personalised nutrition in a representative sample of European consumers, British Journal of Nutrition, 8:1-8, 2008Stewart-Knox BJ, Simpson EE, Parr H, Rae G, Polito A, Intorre F, Andriollo Sanchez M, Meunier N, O’Connor JM,Maiani G, Coudray C, Strain JJ; Taste acuity in response to zinc supplementation in older Europeans, British Journal ofNutrition, 1: 129-136, 2008Strain JJ, Davidson PW, Bonham MP, Duffy EM, Stokes-Riner A, Thurston SW, Wallace JM, Robson PJ, Shamlaye CF,Georger LA, Sloane-Reeves J, Cernichiari E, Canfield RL, Cox C, Huang LS, Janciuras J, Myers GJ, Clarkson TW;Associations of maternal long-chain polyunsaturated fatty acids, methyl mercury, and infant development in theSeychelles Child Development Nutrition Study, Neurotoxicology, 29: 5, 776-782, 2008Wallace JM, Bonham MP, Strain J, Duffy EM, Robson PJ, Ward M, McNulty H, Davidson PW, Myers GJ, Shamlaye CF,Clarkson TW, Molloy AM, Scott JM, Ueland PM; Homocysteine concentration, related B vitamins, and betaine inpregnant women recruited to the Seychelles Child Development Study, American Journal of Clinical Nutrition, 87:391-397, 2008Dr Maria BarnesResearch AssociateContact Details:T: +44 (0)28 70323539m.barnes@ulster.ac.ukDr Barnes has been a member of NICHE since 2004 and her research primarily focuses on dietary modulation ofimmune function and bone health. Dr Barnes’ PhD research focused on the vitamin D status of the general populationand the role of vitamin D in immune and bone health. From 2006, Dr Barnes was involved in a Food StandardsAgency funded project entitled: “Dietary requirements for vitamin D: An investigation of the relative significance ofdietary intake and sunlight on vitamin D status in young and elderly adults.” This was a large intervention study incollaboration with University College Cork investigating the intake of vitamin D required to prevent seasonal vitaminD deficiency in adults aged 20-40 and 65-85 years, to aid in the development of a dietary reference value for vitaminD in these age groups. Dr Barnes is currently working on the follow-up to this study which is also funded by the FoodStandards Agency and is entitled: “Vitamin D status and associated health outcomes: Towards an evidence basis forredefining vitamin D status sufficient to reduce risk of chronic disease”. This study focuses on the impact of vitaminD status on metabolic health, bone health, cardiovascular disease and inflammation. Vitamin D variability parametersincluding vitamin D receptor genotyping are also being assessed.73

Dr Barnes has developed expertise in conducting human intervention studies and specialised laboratory techniques,particularly those associated with vitamin D metabolism and immune function. Her work has also focused on dietaryassessment, body composition and bone mineral density measurements.Other research interests include the effect of vitamin D status on immune conditions, particularly multiple sclerosis,vitamin D requirements during pregnancy and the influence of body composition on nutrient status.Dr Barnes is a Member of: The Nutrition Society, UK; the Multiple Sclerosis Society, UK; the Ulster ImmunologyGroup; and the Institute of Biomedical Science (Licentiate)Press releases:http://news.ulster.ac.uk/releases/2008/4014.htmlhttp://news.ulster.ac.uk/releases/2007/3543.htmlPublications:KD Cashman, TR Hill, AJ Lucey, N Taylor, KM Seamans, S Muldowney, AP FitzGerald, A Flynn, MS Barnes, G Horigan,MP Bonham, EM Duffy, JJ Strain, JMW Wallace & M Kiely; Estimation of the dietary requirement for Vitamin D inhealthy adults; American Journal of Clinical Nutrition, 88: 1535-1542, 2008MS Barnes, MP Bonham, PJ Robson, JJ Strain, AS Lowe-Strong, J Eaton-Evans, F Ginty & JMW Wallace; Assessment of25-hydroxyvitamin D and 1,25-dihydroxyvitamin D 3levels in male and female multiple sclerosis patients and healthycontrols; Multiple Sclerosis, 13: 670-672, 2007Dr Emeir DuffyLecturer in Human NutritionContact Details:T: +44 (0)28 70323543em.duffy@ulster.ac.ukDr Emeir Duffy’s main research interests include the effect of diet, specifically omega-3 fatty acids and vitamin D, onhealth and autoimmune diseases. She also has an interest in marine derived functional foods. During this reportingperiod Dr Duffy was a member of Seychelles Child Development Nutrition Research Group where she was activelyinvolved in the EU 6 th Framework funded project ‘PHIME’ investigating methyl mercury (MeHg) toxicity duringpregnancy. The PHIME consortium consists of 31 partners in 20 countries and will run over five years (2006-2011).In Europe and worldwide there is great speculation as to the effect of toxic metals, in particular MeHg, on childneurodevelopment. Results from these projects will provide information and guidance referring to health impactsassociated with consuming foodstuffs contaminated with toxic metals.Dr Duffy was a member of the vitamin D research group where she was actively involved in the Food Standards Agencyfunded projects ‘An investigation of the relative significance of both dietary sources and sunlight on vitamin D statusand/or functional markers, with particular emphasis on provision of scientific basis for dietary recommendations’ and‘Vitamin D status and associated health outcomes’. The results of the first study have been published and the secondstudy is still ongoing. Vitamin D deficiency is a major public health challenge facing the world and results from thesestudies will impact on public health strategies aimed at targeting this problem.In 2007, Dr Duffy formed partnership with 6 other institutions on the Island of Ireland to form the Marine FunctionalFoods Research Initiative Consortium of which she acts as the PI for the University of Ulster. This initiative is toestablish Ireland as a world-competitor in the area of marine functional foods and identify novel marine derived74

ioactives by enabling technological transfer between academia and industry. To further establish links with the Marineindustry and UU she was successful in being awarded a Fusion project and an Enterprise Ireland funded project toinvestiate the effect of a marine derived calcium supplement on bone health. Median term deliverables include theidentification of dietary compounds that demonstrate anti-cancer activity in vitro together with identifying beneficialeffects of marine-derived compounds on cancer and bone health with potential applications in functional foods.Dr Duffy was involved in a project funded by CAST, in conjunction with the LMC Northern Ireland, investigating theeffect of grass feeding on the omega-3 content of red meat produced in Northern Ireland. Medium term deliverablesinclude the identification of grass-finished red meat as a valuable source of dietary omega-3 bringing added valueto Northern Irish produced beef and lamb. Dr Duffy was actively involved in the Lupus Research Group NorthernIreland and a committee member of the Ulster Immunology Group (UIG). Awarded a DEL funded PhD to furtherinvestiate the effect of vitamin D on systemic lupus erythematosus. In October 2007, she formed part of the localorganising committee for the British Society of Immunology (BSI) 50 th Anniversary Symposium hosted by the UIG inBelfast.Publications:Bonham MP, Duffy EM, Robson PJ, Wallace JM, Myers GJ, Davidson PW, Clarkson TW, Shamlaye CF, Strain J, LivingstoneMB; Contribution of fish to intakes of micronutrients important for fetal development: a dietary survey of pregnantwomen in the Republic of Seychelles; Public Health Nutrition, 6: 1-9, 2008Bonham MP, Duffy EM, Wallace JM, Robson PJ, Myers GJ, Davidson PW, Clarkson TW, Shamlaye CF, Strain JJ; Habitual fishconsumption does not prevent a decrease in LCPUFA status in pregnant women (the Seychelles Child DevelopmentNutrition Study); Prostaglandins Leukot Essent Fatty Acids, 78: 343-350, 2008Davidson PW, Strain JJ, Myers GJ, Thurston SW, Bonham MP, Shamlaye CF, Stokes-Riner A, Wallace JM, Robson PJ,Duffy EM, Georger LA, Sloane-Reeves J, Cernichiari E, Canfield RL, Cox C, Huang LS, Janciuras J, Clarkson TW;Neurodevelopmental effects of maternal nutritional status and exposure to methylmercury from eating fish duringpregnancy; Neurotoxicology, 29: 767-775, 2008Cashman KD, Hill TR, Lucey AJ, Taylor N, Seamans KM, Muldowney S, Fitzgerald AP, Flynn A, Barnes MS, Horigan G,Bonham MP, Duffy EM, Strain JJ, Wallace JM, Kiely M; Estimation of the dietary requirement for vitamin D in healthyadults; American Journal of Clinical Nutrition, 88: 1535-1542, 2008Strain JJ, Davidson PW, Bonham MP, Duffy EM, Stokes-Riner A, Thurston SW, Wallace JM, Robson PJ, Shamlaye CF,Georger LA, Sloane-Reeves J, Cernichiari E, Canfield RL, Cox C, Huang LS, Janciuras J, Myers GJ, Clarkson TW;Associations of maternal long-chain polyunsaturated fatty acids, methyl mercury, and infant development in theSeychelles Child Development Nutrition Study; Neurotoxicology, 29: 776-782, 2008Wallace JM, Bonham MP, Strain J, Duffy EM, Robson PJ, Ward M, McNulty H, Davidson PW, Myers GJ, Shamlaye CF,Clarkson TW, Molloy AM, Scott JM, Ueland PM; Homocysteine concentration, related B vitamins, and betaine inpregnant women recruited to the Seychelles Child Development Study; American Journal of Clinical Nutrition, 87: 391-397, 2008Wright SA, O'Prey FM, McHenry MT, Leahey WJ, Devine AB, Duffy EM, Johnston DG, Finch MB, Bell AL, McVeigh GE.A randomised interventional trial of omega-3-polyunsaturated fatty acids on endothelial function and disease activityin systemic lupus erythematosus; Ann Rheum Dis, 67: 841-848, 200875

Dr Alison GallagherSenior Lecturer in Biomedical Sciences (Human Nutrition)Contact Details:T: +44 (0)28 70323178am.gallagher@ulster.ac.ukDr Gallagher is a Registered Public Health Nutritionist and her current research interests include: investigation of therisk factors for development of disease; health effects of plans and plant components; physical activity and health.Development of risk factors for diseaseDr Gallagher has a longstanding involvement with the Young Hearts Project, a longitudinal investigation of risk factorsfor CVD, obesity and bone health which has provided a valuable dataset on diet, lifestyle and health from adolescenceto early adulthood in a representative sample of individuals from Northern Ireland. In the present reporting periodwork on B-vitamins and bone health and on the relationship between dietary glycaemic index and risk factors formetabolic syndrome were presented at the Nutrition Society Summer meeting. In addition from this data set werecently showed that increased arterial stiffness in young adult women (but not in men) is associated with increasedrisk of metabolic syndrome traits (Ferreira et al. 2007).Health effects of plants and plant componentsDr Gallagher’s early research work focussed on the evaluation of traditional remedies for diabetes. Work undertakenin collaboration with Strathclyde Institute of Pharmacy and Biomedical Sciences on galegine (derived from the herbalGalegine officinalis) and weight loss was published during this reporting period (Mooney et al. 2008). Dr Gallagher’scurrent research interests in this area include: health impact of dietary salicylates – in particular colorectal cancerprevention; the impact of bioactive components on satiety (including a consultancy project with ORAFTI); and healtheffects of modulating postprandial responses.Nutrition, physical activity and healthDr Gallagher’s research interest in this area of physical activity has more recently involved the evaluation ofintervention programmes to address obesity, including work with Community Sports Development, Derry CityCouncil to evaluate a school-based nutrition and physical activity intervention programme (with MP Bonham andfunded by Northern Ireland Chest Heart and Stroke); a long-term physical activity intervention in overweight/obese adults (with a DEL-funded PhD student T Morgan), and commencement of an evaluation of an interventionprogramme in older people (with EEA Simpson, Psychology).Dr Christopher GillLecturerContact details:T: +44 (0)28 70323181c.gill@ulster.ac.ukDr Gill’s research primarily focuses on the effect of diet on cancer, with specific interests in dietary componentsand colorectal cancer (especially phytochemicals in fruits, vegetables and seaweed including, brasscia, olive oil, andberries).Dr Gill also has a specific interest in gut microflora, faecal water toxicity (the aqueous phase of human faeces) andthe implications for colon cancer risk. Dr Gill’s research utilises cell modelling in conjunction with animal and human76

dietary intervention studies to identify potential mechanisms of action. He is currently a member of the scientificadvisory board for the Nordforsk Nordic Centre of Excellence Food and Health Initiative and the Danish PeerReview College.Publications:McCann MJ, Gill CI, Linton T, Berrar D, McGlynn H, Rowland IR; Enterolactone restricts the proliferation of theLNCaP human prostate cancer cell line in vitro; Mol Nutr Food Res, 52: 567-580, 2008Hashim YZ, Rowland IR, McGlynn H, Servili M, Selvaggini R, Taticchi A, Esposto S, Montedoro G, Kaisalo L, Wähälä K,Gill CI. Inhibitory effects of olive oil phenolics on invasion in human colon adenocarcinoma cells in vitro;International Journal of Cancer, 122: 495-500, 2008MacArtain P, Gill CI, Brooks M, Campbell R, Rowland IR; Nutritional value of edible seaweeds; Nutrition Reviews, 65:535-543, 2007Dr Mary Hannon-FletcherLecturer in Cellular PathologyContact Details:T: +44 (0)28 70323247mp.hannon@ulster.ac.ukDr Hannon-Fletcher’s research focuses on Human Nutrition observational, case-controlled and intervention studiesin disease (clinical settings) and in healthy groups. Of particular interest is oxidative stress measured by blood levelsof antioxidants and macromolecule damage (DNA, lipid and carbohydrate) in Type 1 diabetes, renal disease andhealthy control groups. This research also focuses on dietary intake (using food diaries and FFQ) and the relationshipbetween the intake of micro- and macronutrients and their effect on oxidative stress in health and disease.Current research focuses levels of DNA damage and oxidative stress in type 1 diabetes, and was invited to presenther work on ′Nutritional intake and oxidative stress in type 1 diabetes, to the Research and Development office,Endocrinology, Diabetes and Nutrition, Meeting in Coleraine 12 th October 2007, and presented a poster at theDiabetes UK, Professional Conference, Glasgow March 2008: Title: dietary intake in males with type 1 diabetes: arecurrent recommendations adequate?This research is of great interest to individuals with Type 1 diabetes and policy makers alike as it brings new informationon the impact of the diet and disease progression.Multivitamin supplements77

In addition, results of a pilot study conducted with colleagues in the Western Health and Social Care Trust toinvestigate the effect of taking a multi vitamin supplement on renal function and nutrient status in dialysis patients inthe Trust over a three month period were published recently on the University of Ulster web site and on BBC andITV news sites and numerous Renal web news sites, indicating the impact this research has on patient health. It ishoped that this type of intervention may provide the evidence base required to introduce this type of regime intoclinical care in haemodialysis patients in Northern Ireland.DNA damaged Lymphocytes: Left: stained with ethidium bromide right: head and tail indicated.Dr Hannon-Fletcher is a Fellow of the Institute of Biomedical Sciences, a registered Biomedical Scientist with theHealth Professions Council (HPC), a Chartered Scientist with the Science Council, a Registered Nutritionist withthe Nutrition Society and a member of Diabetes UK. In addition, Mary is a member of the scientific and conferenceorganizing committee of the European Childhood Obesity Group 2009 ECOG meeting, to be held in Dublin inSeptember 2008. Mary has keen interest in research ethics and sits on the School of Biomedical Science ResearchEthics Committee and is a member of the HPSS Research Ethical Committees, Northern Ireland (OREC NI).Publications:Hannon-Fletcher MP, Barnett YA; Lymphocyte cytochrome P450 expression: inducibility studies in male Wistar rats;British Journal of Biomedical Sciences, 65: 1-6, 2008McCaffrey TA, Rennie KL, Kerr MA, Wallace JM, Hannon-Fletcher MP, Coward WA, Jebb SA, Livingstone MB; Energydensity of the diet and change in body fatness from childhood to adolescence: is there a relation? American Journalof Clinical Nutrition, 87: 1230-1237, 2008Dr Geraldine HoriganResearch AssociateContact Details:T: +44 (0)28 70323516gb.horigan@ulster.ac.ukDr Horigan’s has been part of NICHE since 2002 and her main research interests are gene-nutrient interactionsin homocysteine metabolism, particularly the interaction between riboflavin the C677T polymorphism inMethylenetetrahydrofolate reductase (MTHFR) and blood pressure. Dietary requirements for vitamin D, bone healthand human intervention studies.Dr Horigan’s research activities include investigating vitamin D status in Irish adults in collaboration with UniversityCollege Cork. This large intervention study funded by the Food Standards Agency examined the intake of vitamin Drequired to prevent seasonal vitamin D deficiency in adults aged 20-85 years.Dr Horigan is currently a Research Associate involved in the Trinity Ulster and Department of Agriculture (TUDA)study one of three studies to be undertaken as part of a large cross-border collaborative project, TUDA is an78

observational study of 6000 patients recruited from both the North and South of Ireland with early evidence ofAlzheimer’s disease, osteoporosis and CVD. This research aims to provide information on current dietary trends,nutrigenomic and lifestyle information. As part of this project Dr Horigan will be involved in recruiting 2000hypertensive patients.Dr Horigan is a Member of: The Nutrition Society, UK; the National Association of Phlebotomists (NAP) (NAPapproved venipuncture (adult) trainer).Publications:Cashman K, Hill T, Lucey A, Taylor N, Seamans K, Muldowney S, Fitzgerald A, Flynn A, Barnes M, Horigan G, Bonham M,Duffy E, Strain JJ, Wallace J, & Kiely M; Estimation of the dietary requirement for vitamin D in healthy adults;American Journal of Clinical Nutrition, 88: 1535-1542, 2008Dickey W, Ward M, Whittle C, Kelly M, Pentieva K, Horigan G, Patton S & McNulty H; Homocysteine and relatedB-vitamin status in coeliac disease: Effects of gluten exclusion and histological recovery; Scandinavian Journal ofGastroenterology, 43: 682-688, 2008Dr Mary KellyResearch AssociateContact Details:T: +44 (0)28 70323969mt.kelly@ulster.ac.ukDr Mary Kelly completed her honours degree in Human Nutrition at the University of Ulster, and continued her studiesthere by completing a Masters of Research degree, before undertaking a PhD in the area of obesity research.Dr Kelly has been a part of NICHE since October 2005 and her main research interests are in the areas of appetite,satiety, the control of food intake and dietary factors influencing overweight and obesity. Dr Kelly has previouslyworked on industry-funded studies which have evaluated the effects of oligofructose enriched inulin on satiety,food intake, blood lipids and satiety hormones. She has also worked on a Food Standards Agency funded projectinvestigating the contribution made by food portion size to food and energy intake.Dr Kelly has recently been appointed as Lecturer in Human Nutrition where she will contribute to teaching andassessment in taught programmes within NICHE as well as being actively involved in working as part of a largemultidisciplinary research team in the Nutrition and Bone Health Research Unit.Publications:Kelly MT, Rennie KL, Wallace JMW, Robson PJ, Welch RW, Hannon-Fletcher MP and Livingstone MBE; Associationsbetween the portion sizes of food groups consumed and measures of adiposity in the British National Diet andNutrition Survey; British Journal of Nutrition (in press)Kelly MT, Wallace JM, Robson PJ, Rennie KL, Welch RW, Hannon-Fletcher MP, Brennan S, Fletcher A and LivingstoneMBE; Increased portion size leads to a sustained increase in energy intake over 4 days in normal weight and overweightmen and women; British Journal of Nutrition (in press)79

Dr Maeve KerrResearch AssociateContact Details:T: +44 (0)28 70323398ma.kerr@ulster.ac.ukDr Kerr’s research interests include obesity in relation to disease risk. Her research projects include the examinationof snacking patterns and snack food intake among children and adolescents at varying risk of obesity. This research,funded by the Food Standards Agency, has provided information on the types of foods that are typically consumed assnacks by UK adolescents. From a public health perspective, the findings may provide scope for policy interventionsto place particular emphasis on reducing typical portion sizes consumed of energy dense snack foods among UKadolescents.Dr Kerr also has an interest in folate, related B vitamins (B6, B12 and riboflavin) and homocysteine in relation todisease risk. Her research activities in this area include examination of folate and B vitamin status among children andadolescents. This research has shown that the well-established progressive increases in homocysteine from 4 to 18years reflect significant decreases in the biomarker status of all four metabolically related B vitamins. These resultsmay facilitate the setting of evidence-based dietary reference values for B vitamins in age and sex specific categories,which are currently unavailable, for potential use within a clinical setting.Dr Kerr’s other research activities include examination of the effects of consumption of green tea on visceral andsubcutaneous abdominal fatness and cardiovascular function. This research aims to examine the effects of greentea catechins on body composition, particularly with respect to visceral fat, in a Western population. Dr Kerr hasgained expertise in the areas of conducting human intervention studies and her work has involved dietary nutritionalassessment, body composition assessment and determination of bone mineral density.Dr Kerr is a Registered Nutritionist (R Nutr 1646) as well as a Member of: The Nutrition Society, UK and theNational Association of Phlebotomists (NAP) (NAP approved venipuncture (adult) trainer).Publications:Kerr MA, Wallace JM, Hannon-Fletcher MP and Livingstone MBE; Snacking patterns among adolescents: A comparisonof type, frequency and portion size between Britain in 1997 and Northern Ireland in 2005; British Journal of Nutrition,101: 122-131, 2009Kerr MA, Livingstone MBE, Bates CJ, Bradbury I, Scott JM, Ward M, Pentieva K, Mansoor MA and McNulty H; Folate,related B vitamins and homocysteine in childhood and adolescence: potential implications for disease risk in laterlife; Pediatrics, 123: 627-635, 2009McCaffrey TA, Rennie KL, Kerr MA, Wallace JM, Hannon-Fletcher MP, Jebb SA, Coward WA and Livingstone MBE;Energy density of the diet and change in body fatness from childhood to adolescence; is there a relationship? AmericanJournal of Clinical Nutrition, 87: 1230-1237, 200880

Professor Barbara LivingstoneProfessor of NutritionContact Details:T: +44 (0)28 70324471mbe.livingstone@ulster.ac.ukProfessor Livingstone’s main research areas/interests are:• Dietary and lifestyle risk factors for obesity, particularly in children and adolescents• Mechanisms of control of appetite, satiety and food intake.• Development of intervention strategies for the prevention of obesity in children and adolescents.• Development of evidence based dietary guidelines for healthy eating• Validity of dietary survey methodologiesExcess body weight is one of the most serious threats to future health. Overweight already affects up to 80% of adultsand 20% of children and adolescents in the EU, with 150 million adults and 15 million children expected to be obeseby 2010. The burgeoning rates of obesity in genetically stable populations suggest that an increasingly obesogenicenvironment is the major driving force behind this epidemic. In the past few decades several key environmental,cultural and economic factors have converged to increase the probability of overeating in the face of reduced energyneeds.In the past five years the group has carried out a number of observational and intervention studies to betterunderstand the impact of energy density, portion size and snacking in inciting overeating. The findings of this work haveshown that portion sizes of many popular snack foods consumed by adolescents (particularly high energy carbonatedand soft drinks) have increased over time. Under fully residential conditions we have convincingly demonstratedthat increased portion size leads to a sustained increase in energy intake. The findings of these studies, which werecommissioned by the Food Standards Agency, have been used to inform FSA strategies aimed at reducing the energyintakes of the UK population.Other associated work being conducted by the group include collaboration with University College Cork on thedevelopment of food consumption databases for development of nutrition and food safety policy, including dietarystrategies for the reduction of obesity. We have collaborated with the University of Nottingham on a Unilever fundedproject to investigate the effect of catechin enriched green tea on visceral fat in adults and analysis of the results iscurrently underway.Professor Livingstone has recently been appointed as Chair of the Data and Research Advisory Group: ObesityPrevention (Fit Futures) by the Department of Health, Social Services and Public Safety (N Ireland). In addition shehas been invited to be an expert member of the International Life Sciences Institute (European Branch)- AppetiteRegulation Task Force.Indicators of Esteem:Invited speaker:• University of North Carolina at Greensboro USA, “Energy density, snacking and portion size: associations withobesity”, February 2008• Food Standards Agency, Belfast, “Nutrient profiling”, June 200881

Memberships of External Committees/Professional bodies:Professor Livingstone is a Member of:• Board of Governors (Scientific), British Nutrition Foundation;• Scientific Advisory Committee, Food Safety Promotion Board (Safefood), Ireland;• Northern Ireland Food Advisory Committee (NIFAC) – Food Standards Agency;• International Life Sciences Institute – European Branch - Appetite Regulation Task Force;• The Nutrition Society, UK;• Association for the Study of Obesity, UK.She is also the Chair of the Data and Research Advisory Group: Obesity Prevention (Fit Futures): Department ofHealth, Social Services and Public Safety (N Ireland).Publications:Irvine PA, Livingstone MBE, Welch RW; Strategies for modifying foods to increase satiety, and reduce subsequentintakes; Agro Food Industry Hi-Tech, 18: 22-24, 2007Carter J, Wilkinson D, Blacker S, Rayson M, Bilzon J, Izard R, Coward A, Wright A, Nevill A, Rennie K, McCaffrey T,Livingstone B; An investigation of a novel three-dimensional activity monitor to predict free-living energy expenditure;Journal of Sports Sciences, 26: 553-561, 2008McCaffrey TA, Rennie KL, Kerr MA, Wallace JM, Hannon-Fletcher MP, Coward, Jebb SA, Livingstone MBE; Energydensity of the diet and change in body fatness from childhood to adolescence: is there a relation? American Journal ofClinical Nutrition, 87: 1230-1237, 2008Moorhead SA, Livingstone MBE, Dunne A, Welch RW; The level of carbonation of a sugar-sweetened beverage preloadaffects satiety and short-term energy and food intakes; British Journal of Nutrition, 99: 1362-1369, 2008Ryan M, Livingstone MBE, Ducluzeau P-H, Salle A, Genaitay M, Ritz P; Is a failure to recognize an increase in foodintake a key to understanding insulin-induced weight gain? Diabetes Care, 31: 448-449, 2008Dr Pamela MageeLecturer in Human NutritionContact Details:T: +44 (0)28 70324360pj.magee@ulster.ac.ukDr Magee’s main research interests include the effects of diet on cancer including breast, prostate and colon cancer.Dr Magee has a particular interest in the effects of phytochemicals, including soy isoflavones and protease inhibitors,on the carcinogenic process which are studied using a variety of in vitro cancer cell models.Dr Magee also has an interest in vitamin D, including its effects on cancer cells in vitro and also vitamin D status andmetabolism in men with prostate cancer.As part of the Marine Functional Foods Research Initiative, the potential health benefits of marine-derivedbioactive compounds in cancer and on bone health are being investigated with a long-term view of functional fooddevelopment.Median term deliverables will include the identification of dietary compounds that demonstrate anti-cancer activityin vitro that warrant further study.82

In addition Dr Magee’s research aims to determine if vitamin D status and/or metabolism is perturbed or differs inmen with prostate cancer compared to controls.Finally, beneficial effects of marine-derived compounds on cancer and bone health will be determined and potentialfunctional foods identified.Dr Magee is a member of the editorial board for the journal Food and Chemical Toxicology, a member of the NutritionSociety and a Registered Nutritionist.Publication:Mortensen A, Kulling SE, Schwartz H, Rowland I, Ruefer C, Rimbach G, Cassidy A, Magee P et al; Analytical andcompositional aspects of isoflavones in food and their biological effects; Molecular Nutrition and Food Research, 53 (inpress)Professor Helene McNultyProfessor of Human Nutrition and DieteticsContact Details:T: +44 (0)28 70324583h.mcnulty@ulster.ac.ukProfessor McNulty’s main research interests are:• Folate and metabolically related B-vitamins in disease prevention: neural tube defects; cancer; cardiovasculardisease; cognitive function• Food folate analysis and bioavailability• Food fortification• Micronutrient requirements/recommendations for humans.Professor Helene McNulty leads the Folate Group within NICHE focusing on the role of folate and the metabolicallyrelated B-vitamins in health and disease. The emphasis of her group’s research is in the area of applied nutrition, i.e.research with clear applications in generating public health policy on nutrition in disease prevention. For example,in the past year, the issue of food fortification with folic acid has been very much on the scientific and politicalagenda in the UK, Ireland and elsewhere in Europe and our team at the University of Ulster has made a significantcontribution to this debate through direct representation (i.e. invited lectures and committee activities) as well asthrough our publications. We have developed several international links (in the US and Europe) and also collaboratewith colleagues in other disciplines in the BMSRI. A major strength of the group is an ongoing and highly successfulcollaboration with Professor John Scott’s team in Trinity College Dublin and we have had several highly productivemeetings between our two centres over the past year. We have recently extended our collaborative links to includekey clinical areas within the health service: gastroenterology; cardiology; obstetrics. As evidenced in this submission,to date these collaborations have lead to new PhD opportunities and clinically relevant publications. The list ofpublications from the Folate Group reflects internationally competitive research in high-ranking journals. In addition,the range of journals covered includes, but extends beyond, the discipline of nutrition. Recently, the group hasembraced the new challenges of how common genetic variations and their interaction with nutrients can influencedisease risk.In the period under review the group has published a total of 10 papers in high impact factor journals (two of whichare first ranked their field), including 2 invited review articles. The group also filed a patent on “Use of riboflavin in thetreatment of blood pressure in people with the MTHFR 677C→T polymorphism”. (International Patent Application:PCT/EP2008/ 001437 ; 23 June 2008) Inventors: Ward M, McNulty H, Scott JM, Horrigan G, Strain JJ, Purvis J.83

Indicators of Esteem:Professor McNulty was recently elected as a Member of the Royal Irish Academy and was invited to speak at thefollowing meetings:“Folates, the need for action. The problem and potential solutions”, Invited expert speaker at the InteractiveSciences and Industry international workshop, Eurreca Week, Montenegro. 10/06/08“Assessment of folate and related B-vitamin intakes”, Invited speaker at the EURRECA project expert workshopon Striving for Excellence in Nutrient Intake Assessment, Prague, Czech Republic. 15/05/08“Folic acid supplementation and optimal health: getting the balance right”, National Institutes of Health,International Speaker Lecture Programme, Washington DC, USA. 16/04/08“Cognitive function – can the right diet slow brain ageing?” Keynote speaker at the Dairy Council conferencefor health and education professionals “An Age-Old Dilemma: Good Nutrition for Older People”, theOdyssey, Belfast. 5/03/08“Folate and related B-vitamins”, Invited expert speaker at the EURRECA project international workshop onMicronutrient Status Methods, Norwich. 19/02/08“Folic acid and related B-vitamins in disease prevention”, Inaugural Annual Science Lecture at the Instituteof Food Science and Technology Northern Ireland Branch meeting, Loughry Food Technology Centre,Cookstown. 12/02/08“Folic acid – why and how it matters”, Keynote speaker at the Association for Spina Bifida and Hydrocephalus(ASBAH) Study Day for Health Professionals, Antrim. 18/10/07Publications:Hoey L, McNulty H, Askin N, Dunne A, Ward M, Pentieva K, Strain JJ, Molloy AM, Flynn C, Scott JM; Impact of avoluntary food fortification policy on folate, related B-vitamin status and homocysteine in healthy adults; AmericanJournal of Clinical Nutrition, 86:1405-1413, 2007Williams E, Stewart-Knox B, McConville C, Bradbury I, Armstrong NC, McNulty H; Folate status and mood: is therea relationship? Public Health Nutrition, 11: 118-123, 2007Dickey W, Ward M, Whittle C, Kelly M, Pentieva K, Horigan G, Patton S, McNulty H; Homocysteine and relatedB-vitamin status in coeliac disease: effects of gluten exclusion and histological recovery; Scandanavian Journal ofGastroenterology, 43: 682-688, 2008McNulty H, Pentieva K, Hoey L, Ward M; Homocysteine and B-vitamins. Proceedings of the Nutrition Society, 67: 232-237, 2008McNulty H and Scott JM; Intake and status of folate and related B-vitamins: considerations and challenges in achievingoptimal status; British Journal of Nutrition, 99: S48-S54, 2008Stanislawska-Sachadyn A, Woodside JV, Brown KS, Young IS, Murray L, McNulty H, Strain JJ, Boreham CA, Scott JM,Mitchell LE, Whitehead AS; Evidence for sex differences in the determinants of homocysteine; Molecular Genetics andMetabolism, 93: 355-362, 2008Stanislawska-Sachadyn A, Brown KS, Mitchell LE, Woodside JV, Young IS, Scott JM, Murray L, Boreham CA, McNulty H,Strain JJ, Whitehead AS; An insertion/deletion polymorphism of the dihydrofolate reductase (DHFR) gene is associatedwith serum and red blood cell folate concentrations in women; Human Genetics, 123: 289-295, 200884

Wallace JMW, Bonham MP, Strain JJ, Duffy EM, Robson PJ, Ward M, McNulty H, Davidson PW, Myers GJ, Shamlaye C,Clarkson TW, Molloy AM, Scott JM and Ueland PM; Homocysteine concentration, related B-vitamins and betaine inpregnant women recruited to the Seychelles Child Development Study; American Journal of Clinical Nutrition, 87: 391-397, 2008Hoey L, McNulty H, McCann EME, McCracken KJ, Scott JM, Blaznik Marc B, Molloy AM, Graham C, Pentieva K; Layinghens can convert high doses of folic acid added to the feed into natural folates in eggs providing a novel source offood folate; British Journal of Nutrition (in press)Kerr MA, Livingstone B, Bates CJ, Bradbury I, Scott JM, Ward M, Pentieva K, Mansoor MA, McNulty H; Folate, related Bvitamins and homocysteine in childhood and adolescence: potential implications for disease risk in later life; Pediatrics(in press)Dr Patrick NaughtonSenior Lecturer in Medical MicrobiologyContact Details:T: +44 (0)28 70324689pj.naughton@ulster.ac.ukDr Patrick Naughton’s research focuses on diet and bacterial interactions in the gastrointestinal tract, with a particularemphasis on antibiotic resistance in food-poisoning bacteria and the use of myoelectrical techniques (with Dr ViolettaNaughton) in the investigation of the effects of diet and bacteria on gut motility.In the past five year’s his research has focussed on the role of prebiotics in the gastrointestinal tract and their influenceon both the normal flora and gastrointestinal pathogens such as Salmonella and other Gram negative pathogens andin developing methods to identify antibiotic resistance patterns in food borne pathogens (with Prof James Dooley). Asubstantial proportion of Dr Naughton’s research is funded by SafeFood (Food Safety Promotion Board).Dr Jacqueline O’ConnorAssociate Head of SchoolSchool of Biomedical SciencesContact Details:T: +44 (0)28 70324186jm.oconnor@ulster.ac.ukDr O’Connor’s research interests include: Trace elements in health and disease; trace elements and immune functionand DNA damage; nutrition and immune function; nutrition and cognitive function and mood, psychoneuroimmunologyand choline and human health.She is principal investigator of the Ulster part of the ZENITH project. This, recently completed, multidisciplinary projectaimed to provide data on the beneficial and/or adverse effects on mental and physical health of zinc supplementationin ageing Europeans, in order to evaluate the need for dietary recommendations specific to this population. Effectsof zinc supplementation on relevant micronutrient status and intestinal absorption of zinc have been evaluated.Cognitive function and psychological factors including mood, food choice and taste were also monitored. Effects ofzinc on biomarkers health including those of immune status, thyroid function, oxidative status, lipid metabolism andbone turnover were also investigated. In addition interactions between immune function and psychological measures85

were examined. The intervention and analyses stages of this project has been completed and to date there have beena significant number of publications associated with. It involved collaboration with CeNeS Ltd who were responsiblefor the expertise and equipment necessary for carrying out the computerised tests of cognitive function and for thecollection and collation of the resulting data. CeNeS Ltd is the sole supplier of the Cambridge NeuropsychologicalTest Automated Battery (CANTAB) which is a computerised battery of tests for neuropsychological evaluation.Dr O’Connor is also involved in the Northern Ireland Fish Oil Study (NIFOS) which is examining the impact of fish oilsupplementation on psychological health of older adults. It is hypothesised that marine (fish oil) n-3 polyunsaturatedfatty acids (n-3 PUFA) will modulate the immune system leading to changes in vascular blood flow to brain andthereby affecting cognitive function. There is a growing body of evidence that demonstrates that the long chain n-3PUFA, DHA is essential for cognitive development in animals and infants and children. However, to date surprisinglylittle work has been done to examine the effects of n-3 PUFA on cognitive decline in humans. The little that hasbeen reported is mainly observational work. It is proposed that the 55-70 years age group, an age group thatshows a marked increase in mild cognitive impairment, may benefit greatly from supplementation. We are currentlycarrying out a long-term (6 months) intervention study in older adults, supplementing with fish oil to investigatethe impact on psychological function. Seven Seas Ltd have kindly supplied fish oil supplements for this study whichis in collaboration with the School of Psychology at Ulster. An extension of this study is also investigating attitudestowards the use of fish oil supplements, comparing the attitudes and perceived knowledge of consumers and nonconsumers.To date there is virtually no literature on this topic, so it is hoped that this original work will identifypotential factors which might inform the decision to either supplement with fish oil or to choose not to take suchsupplements. This information is likely to be of benefit in relation to health promotion, in encouraging consumptionof fish oil supplements, or to the supplement production industry.Publications:Hininger-Favier I, Andriollo-Sanchez M, Arnaud J, Meunier N, Bord S, Graham C, Polito A, Maiani G, O'Connor JM,Coudray C, Roussel AM; Age- and sex-dependent effects of long-term zinc supplementation on essential trace elementstatus and lipid metabolism in European subjects: the Zenith Study; British Journal of Nutrition, 97: 569-578, 2007Hodkinson CF, Kelly M, Alexander HD, Bradbury I, Robson PJ, Bonham MP, O’Connor JM, Coudray C, Strain JJ andWallace JM; Effect of Zinc Supplementation on the Immune Status of Healthy Older Individuals Aged 55–70 Years: theZENITH Study; Journal of Gerontology A Biol Sci Med Sci; 62: 598-608, 2007Intorre F, Polito A, Andriollo-Sanchez M, Azzini E, Raguzzini A, Toti E, Zaccaria M, Catasta G, Meunier N, Ducros V,O'Connor JM, Coudray C, Roussel AM, Maiani G; Effect of zinc supplementation on vitamin status of middle-aged andolder European adults: the ZENITH study; European Journal of Clinical Nutrition, 2007Simpson EE, McConville C, Rae G, O'Connor JM, Stewart-Knox BJ, Coudray C, Strain JJ; Salivary cortisol, stress andmood in healthy older adults: The Zenith study; Biological Psychology, 78: 1-9, 2008Stewart-Knox BJ, Simpson EE, Parr H, Rae G, Polito A, Intorre F, Andriollo Sanchez M, Meunier N, O'Connor JM,Maiani G, Coudray C, Strain JJ; Taste acuity in response to zinc supplementation in older Europeans; British Journal ofNutrition, 99:129-136, 200886

Dr Kristina PentievaSenior LecturerContact Details:T: +44 (0)28 70324675k.pentieva@ulster.ac.ukDr Pentieva is a member of Folate Research Group within NICHE. Her main research interests are in the fieldof folate and metabolically related B-vitamins and their role in health and disease. In particucar, she is involved ininvestigating bioavailability of different folate derivatives and the bioavailability of folate from various food matricesin healthy subjects including people with common polymorphisms for genes encoding enzymes involved in folatemetabolism. In addition, she is interested in the influence of gender, age and genotype on folate and B-vitamin statusin view of the implications for dietary recommendations for different population groups and food fortification policy.Another object of her interests is the development of novel functional foods enriched with natural folates as analternative approach to fortification.Dr Pentieva is a member of The Nutrition Society (UK) and the European Academy of Nutritional Sciences.Publications:Hoey L, McNulty H, Askin N, Dunne A, Ward M, Pentieva K, Strain JJ, Molloy AM, Flynn CA, Scott JM; Impact of avoluntary food fortification policy on folate, related B-vitamin status and homocysteine in healthy adults; AmericanJournal of Clinical Nutrition, 86:1405-1413, 2007McNulty H, Pentieva K, Hoey L and Ward W; Folic acid and related B-vitamins in disease prevention; Food Science andTechnology; 21: 41-43, 2007Bekaert B, Cooper ML, Green F, McNulty H, Pentieva K, Scott JM, Molloy AM, Rayman MP; Effect of selenium statusand supplementation with high-selenium yeast on plasma homocysteine and B vitamin concentrations in the UKelderly; Molecular Nutrition and Food Research, 52: 1324-1333, 2008Dickey W, Ward M, Whittle CR, Kelly MT, Pentieva K, Horigan G, Patton S, McNulty H; Homocysteine and relatedB-vitamin status in celiac disease: effects of gluten exclusion and histological recovery; Scandinavian Journal ofgastroenterology, 43: 682-688, 2008McNulty H, Pentieva K, Hoey L and Ward W; Homocysteine, B-vitamins and CVD; Proceedings of the Nutrition Society,67: 232-237, 2008Dr Ruth PriceResearch AssociateContact Details:T: +44 (0)28 70323515rk.price@ulster.ac.ukDr Price has been a member of NICHE since 2000, and her main research interest is in the area of wholegrains andheath. She is currently the lead researcher on the EU-funded Integrated Project “Healthgrain– exploiting bioactivity ofEuropean cereal grains for improved nutrition and health benefits”. The aim of this work is to increase understandingof the mechanisms whereby minor components present in cereals (particularly wholegrain wheat foods) impacton human physiology, and thus may contribute to the prevention or alleviation of heart disease and other diseases.87

Within this work both short-term and longer-term clinical trials are being used to evaluate the uptake and healthbenefits of these potentially bioactive wholegrain components. Of particular interest is the role and potential of themicronutrient betaine within the wholegrain. The structure of this project allows findings to be communicated tocereal producers / processors, aiding the production of foods rich in protective wholegrain components, as well ashealth professionals, helping to support current European nutritional guidelines and health-claim legislation.As part of this work, Dr Price has developed expertise in conducting human intervention trials as well as inspecialised laboratory techniques determining clinical risk markers for health. Particular analysis of interest includesinflammation status, oxidative stress as well as micronutrient and phytochemical status. Her work has also involveddietary nutritional assessment as well as the determination of bone mineral density.Other research interests include the phenolic and antioxidant activity of foods including cereals and fruit juices, andDr Price has been involved with a project with Agri-Food & Biosciences Institute (AFBI), Belfast, assessing the effectsof processing on these parameters. In addition Dr Price continues to be involved in FUSION projects and mentorsstudents in the area of product development and functional foods.Dr Price is a Member of The Nutrition Society, UK.Publication:Price RK, Welch RW, Lee-Manion AM, Bradbury I, Strain JJ. Total phenolics and antioxidant potential in plasma andurine of humans after consumption of wheat bran; Cereal Chemistry, 18: 152-157, 2008Dr Barbara Stewart-KnoxSenior Lecturer in Biomedical SciencesContact Details:T: +44 (0)28 70324781b.knox@ulster.ac.ukDr Stewart-Knox has an interest in the following research themes:• Food choice, psycho-social and sensory determinants• Nutrient mediated psychological functions• Food product development related consumer issues• Attitudes toward infant feeding• Health promotion issues.However, Dr Stewart-Knox’s main research interest is the psycho-social aspects of food.NICHE conducts research into a range of food-related consumer issues and psychological functions using a rangeof methodologies both quantitative and qualitative in the following areas:• Pre- and post-launch food product evaluation• Determinants of food choice:Attitudes toward food related issuesSensory perceptions of food.• Investigation into food/nutrient mediated psychological functions:Affective88

CognitiveBehavioural.• Understanding health behaviour:Infant feedingSmoking.Publications:Simpson EE, McConville C, Rae G, O'Connor JM, Stewart-Knox BJ, Coudray C, Strain JJ; Salivary cortisol, stress andmood in healthy older adults: The Zenith study; Biological Psychology, 78: 1-9, 2008Stewart-Knox BJ, Bunting BP, Gilpin S, Parr HJ, Pinhão S, de Almeida MDV & Gibney M; Attitudes toward genetic testingand personalised nutrition in a representative sample of European consumers; British Journal of Nutrition [E-publicationcopy Ahead of print] (2008)Stewart-Knox BJ, Simpson EE, Parr H, Rae G, Polito A, Intorre F, Andriollo Sanchez M, Meunier N, O'Connor JM, MaianiG, Coudray C, Strain JJ; Taste acuity in response to zinc supplementation in older Europeans; British Journal of Nutrition,99:129-136, 2008Williams E, Stewart-Knox BJ, McConville C, Bradbury I, Armstrong N & McNulty H; Folate Status and Mood: Is Therea Relationship? Public Health Nutrition, 11: 118-123, 2008Dr Julie WallaceSenior Research FellowDr Wallace’s primary research focuses on modulation of immune function by diet and also the relationship betweenbody composition and immune function/inflammation.Alterations in immune function and inflammation are associated with the major diseases on the developed world,including cardiovascular disease, cancer and dementia. While it has been recognized for many years that deficiencyof particular nutrients can lead to impaired immunity and susceptibility to infection, suboptimal status of nutrients,as is evident in the Western World can also lead to impaired immune function. NICHE conducts fundamentalresearch assessing changes in immune function associated with normal physiological processes and also associatedwith pathological disease processes. The group also researches the complex relationship between specific nutrientsand immune function.In the last five years the group has carried out observational research and reported changes in immunological andhaemostatic function in pregnancy, which protect the mother and fetus from pregnancy complications. This researchalso highlighted the potential benefits for pregnant women in continuing folic acid supplementation throughoutpregnancy. Research has also shown that the immune system of men and women aged 55-70years shows differentassociations with age, with ageing of the immune system in women possibly delayed owing to the protective actionsof the female hormones.The influence of specific micronutrients including omega-3 fatty acids, zinc, γ-tocopherol and vitamin D in modulatingimmune function is a particular interest of the research group and a number of studies have been undertaken andare currently being performed in this area. The intervention studies focus on a nutritional approach, providing89

micronutrient supplementation at a level which can be achieved by dietary strategies with whole foods or functionalfoods.Dr Mary WardSenior Lecturer in Human Nutrition and DieteticsContact Details:T: +44 (0)28 70323076mw.ward@ulster.ac.ukDr Ward’s is a key member of the Folate Research Group. Her research focuses primarily on the role of B-vitaminsand homocysteine in healthy and diseased (particularly cardiovascular disease) populations and much of this work isconducted in collaboration with local NHS trusts.One area of particular interest is the interaction between folate, riboflavin and a common polymorphism (C677T)in one of the folate metabolising enzymes methylenetetetrahydrofolate reductase. Ongoing work indicates thatriboflavin, administered at a dietary level, appears to be a potent modulator of Blood Pressure in individuals whocarry this particular polymorphism (approximately 10% of the UK / Irish population) and has led to a patent beingfiled on “Use of riboflavin in the treatment of blood pressure in people with the MTHFR 677C→T polymorphism”.(International Patent Application: PCT/EP2008/ 001437 ; 23 June 2008) Inventors: Ward M, McNulty H, Scott JM,Horrigan G, Strain JJ, Purvis J.This gene/nutrient relationship will be further investigated in a large study (involving 6000 participants) funded bythe Irish Department of Agriculture & Food/Department of Health and Children, conducted by the team at UlsterUniversity and collaborators at both Trinity College Dublin and University College Dublin.Other interests include B-vitamin requirements in different population groups and aspects of folate bioavailability.Publications:Hoey L, McNulty H, Askin N, Dunne A, Ward M, Pentieva K, Strain JJ, Molloy AM, Flynn C, Scott JM; Impact of avoluntary food fortification policy on folate, related B-vitamin status and homocysteine in healthy adults; AmericanJournal of Clinical Nutrition, 86: 1405-1413, 2007Dickey W, Ward M, Whittle C, Kelly M, Pentieva K, Horigan G,Patton S and McNulty H; Homocysteine and relatedB-vitamin status in coeliac disease: effects of gluten exclusion and histological recovery; Scandanavian Journal ofGastroenterology, 43: 682-688, 2008McNulty H, Pentieva K, Hoey L, Ward M; Homocysteine and B-vitamins. Proceedings of the Nutrition Society, 67: 232-237, 2008Wallace JMW, Bonham MP, Strain JJ, Duffy EM, Robson PJ, Ward M, McNulty H, Davidson PW, Myers GJ, Shamlaye CF,Clarkson TW, Molloy AM, Scott JM and Ueland PM; Homocysteine concentration, related B-vitamins and betaine inpregnant women recruited to the Seychelles Child Development Study, American Journal of Clinical Nutrition, 87: 391-397, 200890

Professor Rob WelchProfessor of Food Science and NutritionContact Details:T: +44 (0)28 70324205rw.welch@ulster.ac.ukProfessor Welch’s research is focussed on three strands:• Cereals, phytochemicals and health;• The influence of food characteristics on appetite and satiety and intake;• The potential health effects of food-derived peptides.Professor Welch is Principal Investigator for the University of Ulster contribution to “Healthgrain– exploitingbioactivity of European cereal grains for improved nutrition and health benefits” an EU-funded Integrated Project,running from 2005-2010, that has over 40 partners from across Europe. The overall aim of the work at the Universityis to increase understanding of the mechanisms whereby minor components present in cereals (particularly wholegrainwheat foods) impact on human physiology, and thus may contribute to the prevention or alleviation of heartdisease and other diseases. Initial short-term studies that evaluated the uptake of these components by humans arebeing followed by longer–term human interventions that evaluate a range of biomarkers for heart disease and otherpathologies. This research, which has been facilitated by inputs from other research centres, will provide new insightsinto the role of whole-grain foods in the alleviation of heart disease and other conditions.The identification of food characteristics that influence appetite and satiety offers the potential for the developmentof foods that may help to prevent or alleviate overweight and obesity. This research is of relevant to public healthinitiatives, and to the food industry. Ongoing research has shown that food characteristics that are often neglectedin mainstream nutrition can influence appetite and satiety, and affect food and energy intake. These characteristicsinclude physical structure (solids vs liquids; gas/air content), and the presence of components such as non-digestiblecarbohydrates (NDC). Professsor Welch is Principal Investigator on an industry-funded study that is evaluating aNDC food ingredient for effects on satiety, food intake, blood lipids and satiety hormones. It is anticipated that thisresearch may assist in the substantiation of health claims.The research into the potential health effects of food-derived peptides has been conducted in collaboration withother colleagues in BMSRI. This work challenges the conventional view that dietary protein is completely brokendown into amino acids prior to absorption, and is assessing the potential for diet-derived peptides to be absorbedinto the plasma and to exert physiological effects of relevance to health and disease.Prof Welch was an invited speaker at 1st European BENEO Scientific Symposium, Brussels, April 11, 2008, EnergyMetabolism of Functional Carbohydrates: New Findings; Appetite and food intake regulation: human data.Publications:Moorhead SA, Livingstone MBE, Dunne A, Welch RW; The level of carbonation of a sugar-sweetened beverage preloadaffects satiety and short-term energy and food intakes; British Journal of Nutrition, 99: 1362-1369, 2008Price RK, Welch RW, Lee-Manion AM, Bradbury I, Strain JJ; Total phenolics and antioxidant potential in plasma andurine of humans after consumption of wheat bran; Cereal Chemistry, 85:152-157, 2008Irvine PA, Livingstone MBE, Welch RW; Strategies for modifying foods to increase satiety, and reduce subsequentintakes; Agro Food Industry Hi-Tech, 18: 22-24, 200791

10. STEM CELL & EPIGENETICS RESEARCH GROUPThe Stem Cells & Epigenetics Group has been exploiting the developing theme of stem cell research. The Group isequipped with transgenic mouse facilities, including a microinjection station with Nikon microscope and Narashigemicromanipulators, Nikon Eclipse 600 upright fluorescence microscope and SPF mouse facility with dedicatedtechnical staff. There are also designated stem cell laboratories for culture, differentiation and visualisation of stemcells.The research activities of the group have centred upon the stem cells in the blood and gonads and the group haveconcentrated on five main project areas:• Immunosenescence through decrease of DNA repair capacity with age, as measured in clonal populations of Tcells from donors of different ages.• Epigenetic reprogramming in normal development and in disease, including work into fundamental aspects ofDNA methylation through construction and analysis of DNA methylase-defective mouse lines.• Germ cell development and its relevance for infertility syndromes: the role of candidate genes in maleinfertility.• Stem cell function and reprogramming during the ontology of leukaemia, to identify potential new drug treatmentsas well as exploring the possibility of expanding stem cells from fetal cord.• Examining the links between DNA repair and methylation, leading to insights into mechanisms of drug resistancein tumours and potential benefits in terms of treatment selection.92

MEMBERS OF THE GROUPDr Colum Walsh, Group LeaderSenior Lecturer in Molecular GeneticsContact details:T: +44 (0)28 70324484cp.walsh@ulster.ac.ukDr Walsh’s main research interests are in the fields of Epigenetics and Fertility.We are currently focused on the role of DNA methylation in reprogramming gene expression during germ celldevelopment, particularly in the oocytes. This process is extremely important for resetting genes and avoidingdevelopmental disease syndromes such as Beckwith-Weidemann and Angelman.We have also found a novel link between DNA modification and DNA repair which may not only explain someof the puzzling features of colon cancer cells but also lead to novel therapeutic approaches in the future. Wehave created cell lines deficient in MLH1 (a repair protein) and DNMT1 (a DNA modification protein) and haveextensive preliminary data on these. We wish to exploit the model systems we have created to examine moreclosely the cross-talk between the modification and repair systems and the effects of perturbing each on cellularresistance to chemotherapeutic drugs.Further information on this Group’s research activities can be found at the following website: http://www.science.ulster.ac.uk/stemcell/index.html93

Publications:Lees-Murdock DJ, Lau HT, Castrillon DH, De Felici M, Walsh CP; DNA methyltransferase loading, but not de novomethylation, is an oocyte-autonomous process stimulated by SCF signaling; Developmental Biology, 321: 238-250, 2008Related ArticlesLees-Murdock DJ, Walsh CP; DNA methylation reprogramming in the germ line; Epigenetics, 3: 5-13, 2008 [Review]Presentations at conferences:Speaker, Joint UK/German Epigenetics meeting, Überherrn, Germany 2007Speaker, UK Stem Cell Network regional meeting, Antrim, 2007Speaker, XIV International Workshop on the Development and Function of the Reproductive Organs, Frascati,Italy, 2008Speaker, Cancer RRG Annual Meeting, Antrim, Northern Ireland, 2008Dr Robin W FreeburnLecturer in Haematology and ImmunologyContact details:+44 (0)28 70324606 rw.freeburn@ulster.ac.ukMain research interests:The main area of investigation in the lab is the role of Wnt proteins in lymphocytic leukaemia. Two projects are currentlylooking at chronic lymphocytic leukaemia (CLL) and acute lymphoblastic leukaemia (ALL) to identify abnormalitiesand signalling defects in the Wnt pathways that may contribute towards these leukaemias. In collaboration withBelfast City Hospital, a mix of molecular analysis, protein pathway analysis and cell based assays are used to investigateleukaemic cell lines and patient samples. Another area of interest is the regulation of intracellular signalling pathwaysin T cells, in particular the role played by inositol phosphatases in negatively regulating pathways activated by theCD28 and CD3 receptors.Immunobiology and fluorescent imaging techniques are being used to investigate the activation and control ofsignalling pathways such as PKB, DOK and Map kinases. Specific projects are looking at pathways downstream of PI3kinases and the role of the inositol phosphatases, SHIP and PTEN, in this regulation. PTEN is a commonly mutatedtumour suppressor gene and its role of in the leukaemogenesis of lymphocytic malignancies is another area of activeresearch. This includes investigation into the role of genetic mutation, especially single nucleotide polymorphisms,in the pathogenesis of lymphocytic leukaemias. The expression of SHIP isoforms has been shown to change with94

lymphoid development. With the use of haemopoietic stem cells, we are examining mRNA and protein expressionof these isoforms as lymphoid progenitors mature and differentiate during haemopoiesis, which should expand thecurrent understanding on the role of inositol phosphatases in lymphocyte development. Other areas of researchinclude Umbilical cord blood stem cell transplantation, Proteomic analysis of haemopoietic differentiation and theregulation of embryonic stem (ES) cell self-renewal.Publications:Corrigan PM, Dobbin E, Freeburn RW, Wheadon H; Patterns of Wnt/Fzd/LRP Gene Expression during EmbryonicHematopoiesis; Stem Cells & Development, 2008 Sep 18. [Epub ahead of print]Dobbin E, Corrigan PM, Walsh CP, Welham MJ, Freeburn RW, Wheadon H; Tel/PDGFRbeta inhibits self-renewal anddirects myelomonocytic differentiation of ES cells; Leukaemia Research, 32: 1554-1564, 2008Dr Freeburn is a Member of the Scientific Committee of the Northern Ireland Leukaemia Research Fund, as well asa Member of the Haematology Association of Ireland.Presentations at Conferences:P Corrigan, E Dobbin, H Wheadon and Robin Freeburn; Wnt3a and Wnt5a play a key role in establishing haemopoieticdevelopment during mouse embryogenesis. Haematology Association of Ireland, Sligo, October 2007E Dobbin, C Graham, Robin Freeburn and H Wheadon; Regulated Expression of Tel/PDGFR beta tyrosine kinase inembryonic stem cells drives myelopoiesis. Haematology Association of Ireland, Sligo, October 2007P Corrigan, E Dobbin, H Wheadon and Robin Freeburn; Wnt3a and Wnt5a play a key role in establishing haemopoieticdevelopment during mouse embryogenesis. UK National Stem cell Network Scientific Conference, Edinburgh, April 2008.Dobbin E, Corrigan P, Walsh CP, Welham MJ, Freeburn RW, Wheadon H; Regulated expression of Tel/PDGFRbetainhibits self-renewal and directs myelomonocytic differentiation of ES cells. UK National Stem cell Network ScientificConference, Edinburgh, April 2008.Dr Diane Lees-MurdockLecturer in Biomedical SciencesContact details:T: +44 (0)28 70323166dj.lees@ulster.ac.ukResearch InterestsDr Lees Murdock’s main research interests are in the area of epigenetic reprogramming and in particular:• Methylation dynamics in the mouse oocyte• Establishment of paternal imprints in male primordial germ cells• Methylation of various classes of repeat sequences in the mouse germ line• Post-transciptional control of DNA methyltransferases and DNA methylation reprogramming• Role of DNA methylation in stem cell plasticityDNA methylation is essential for normal development to ensure proper regulation of gene expression, chromosomestability, genomic imprinting, X chromosome inactivation and stem cell differentiation. Anomalies in this process arebelieved to limit the success of in vitro fertilisation (IVF) and growing evidence indicates that epigenetic alterationsmay be involved in diseases such as cancer, autoimmune and psychiatric disorders.95

Publications:Lees-Murdock DJ, Lau HT, Castrillon DH, De Felici M, Walsh CP; DNA methyltransferase loading, but not de novomethylation, is an oocyte-autonomous process stimulated by SCF signaling; Developmental Biology, 321: 238-250,2008Related ArticlesLees-Murdock DJ, Walsh CP; DNA methylation reprogramming in the germ line; Epigenetics, 3: 5-13, 2008 [Review]Dr Helen WheadonLecturer in ImmunologyResearch InterestsSignal transduction pathways involved in stem cell self-renewal, haemopoietic and angiogenic development. The use ofstem cell models to study the cellular signalling events involved in the progression of myeloid leukaemias, to identifyand target key molecules for therapeutic intervention.96

Publications:Corrigan PM, Dobbin E, Freeburn RW, Wheadon H; Patterns of Wnt/Fzd/LRP Gene Expression during EmbryonicHematopoiesis; Stem Cells & Development, 2008 Sep 18. [Epub ahead of print]Dobbin E, Corrigan PM, Walsh CP, Welham MJ, Freeburn RW, Wheadon H; Tel/PDGFRbeta inhibits self-renewal anddirects myelomonocytic differentiation of ES cells; Leukaemia Research, 32: 1554-1564, 2008Dr Olaf SunnotelResearch AssociateContact details:T: +44 (0)28 70323545o.sunnotel@ulster.ac.ukDr Sunnotel worked during this period initially with Dr Walsh on an Invest Northern Ireland-sponsored projectexamining a candidate gene which is mutated in infertile azoospermic males. For the latter part of the reportingperiod he began work with Dr Lees-Murdock on post-transcriptional control of DNMT1 expression.97

11. SYSTEMS BIOLOGY RESEARCH GROUPThe strategy of the Systems Biology Research Group (SBRG) is focused on the bioinformatics and computationalelements of the now strongly growing interdisciplinary field of systems biology. Systems biology is defined as “thequantitative analysis of the dynamic interactions between several components of a biological system and aims to understand thebehaviour of the system as a whole. It applies the concepts and methodologies of systems theory and engineering to the studyof complex biological systems through iteration between computational and mathematical modelling and experimentation.Systems Biology is a tool to increase understanding of the system, to develop more directed experiments and finally allowpredictions”.This strategic view on the Group’s research aligns well with national and international priorities. Complementing thisresearch strategy, academic members of the Group are currently in the process to develop a basic teaching coursein systems biology. As personalized medicine seems to find its way into national and international research agendas,first steps have been taken to explore this dimension in the context of systems biology.The main research themes investigated by the SBRG, include modelling of interactions in kinase/phosphatase systems;modelling and simulation of gene regulatory networks; qualitative modelling of the bile acid and xenobiotic system;computational study of the genetic causes of LQT syndrome; and various aspects of management and analysis ofbiological information.In the reporting period, members of the Group published a considerable number of articles in high-calibre internationaljournals and conferences (some of which were included in the 2008 RAE submission) and was awarded considerablelevels of research grants. The Group has also consolidated its research partner network nationally and internationally,including renowned organizations such as the University of Queensland, Brisbane, Australia; the Haifa Institute ofTechnology, Israel; Korea Advanced Institute of Science and Technology (KAIST), Republic of Korea. Some membersof the Group have been members of international advisory boards and journal editorial boards.The Group has 5 dual processor servers that provide Web services and content-management software, groupware,file and database services (Oracle Enterprise server 10G) as well as Grid services (Globus and CONDOR). Forlarge-scale computing tasks, there is a 64-way Itanium Altix 3700 supercomputer with 128GB of addressable memoryand 8 TB of disk storage. Projects using this system range from protein-unfolding simulations to tracing of stainedstructures in large image stacks.98

MEMBERS OF THE GROUPProfessor Werner Dubitzky, Group LeaderProfessor of BioinformaticsContact details:T: +44 (0)28 70324478w.dubitzky@ulster.ac.ukProfessor Dubitzky’s main research activities in the reporting period included:• preparation of research papers for RAE 2008;• preparation of research grant applications;• research in modelling, analyzing and simulating biomedical systems;• working on new edited volumes (books and special issues in international journals and an encyclopedia);• management and research on ongoing research projects;• networking.The key themes of Werner’s research activities in this reporting period revolved around computational elementsof systems biology and e-science (which are both part of national and European research priorities). These themeswill continue to be his research focus into the future, perhaps with a stronger element of personalized medicine,dynamical modelling and integration of heterogeneous information for modelling and simulation of biological systemsand scientific knowledge discovery.Publications:Romberg M, Benfenati E & Dubitzky W; Open Computing Grid for Molecular Sciences in E-G. Talbi & A. Zomaya(editors), Grids for Bioinformatics and Computational Biology, Wiley Book Series on Parallel and Distributed Computing;John Wiley & Sons, New York, pp1-22. ISBN: 978-0-471-78409-8, 2007Cashman KD, Hill TR, Cotter AA, Boreham CA, Dubitzky W, Murray L, Strain J, Flynn A, Robson PJ, Wallace JM & KielyM; Low vitamin D status adversely affects bone health parameters in adolescents, American Journal of Clinical Nutrition,87: 1039-1044, 2008Fuß H, Dubitzky W, Downes CS & Kurth MJ; Src family kinases and receptors: analysis of three activation mechanismsby dynamic systems modelling; Biophysical Journal, 94, 1995-2006, 2008Hill TR, Cotter AA, Mitchell S, Boreham CA, Dubitzky W, Murray L, Strain JJ, Flynn A, Robson PJ, Wallace JM, Kiely M& Cashman KD; Vitamin D status and its determinants in adolescents from the Northern Ireland Young Hearts 2000cohort; British Journal of Nutrition, 99: 1061-1067, 2008Kravtsov V, Schuster A, Carmeli D, Kurowski K & Dubitzky W; Grid-enabling complex system applications withQosCosGrid: An architectural perspective, in Proceedings of the International Conference on Grid Computing andApplications (GCA'08), Las-Vegas, USA, 2008Kravtsov V, Carmeli D, Dubitzky W, Orda A, Schuster A, Silberstein M & Yoshpa B; Quasi-Opportunistic Supercomputingin Grid Environments, in Proceedings of the International Conference on Algorithms and Architectures, Cyprus, 233-244,2008Kravtsov V, Swain M, Dubin U, Dubitzky W & Schuster A; A Fast and Efficient Algorithm for Topology-AwareCoallocation, in Proceedings of the International Conference on Computational Science, Krakow, Poland, 274-283, 200899

Kravtsov V, Swain M, Schuster A, Dubitzky W and Dubin U; Grid computing solutions for distributed repositories ofprotein folding and unfolding simulations, in Proceedings of the International Conference on Computational Science (ICCS2008), Poland, 274-283, 2008Sánchez A, Montes J, Dubitzky W, Valdés JJ, Pérez MS & de Miguel P; Data Mining Meets Grid Computing: Time toDance? in W. Dubitzky (editor); Data Mining Techniques in Grid Computing Environments, Wiley, pp. 1-16, 2008Stankovski V, Swain M, Kravtsov V, Niessen T, Wegener D, Röhm M, Trnkoczy J, May M, Franke J, Schuster A & DubitzkyW; Digging Deep into the Data Mine with DataMiningGrid; IEEE Internet Computing, 12: 69-76, 2008Stankovski V, Swain M, Kravtsov V, Niessen T, Wegener D, Kindermann J & Dubitzky W; Grid-enabling data miningapplications with DataMiningGrid: An architectural perspective; Future Generation Computer Systems, 24: 259–279,2008Swain M, Mandel JJ and Dubitzky W; Comparing Grid Computing Solutions for Reverse-Engineering Gene RegulatoryNetworks, in Proceedings of the International Conference on Computational Science (ICCS 2008), Poland, 106-115, 2008Swain M, Ostropytskyy V, Silva CG, Stahl F, Riche O, Brito RMM, Dubitzky W; Grid Computing Solutions for DistributedRepositories of Protein Folding and Unfolding Simulations; Proceedings of the International Conference on ComputationalScience (ICCS 2008), Krakow, Poland, 70-79, 2008Gulyas L, de Back W, Szemes G, Kurowski K, Dubitzky W and Kampis G; Templates for Distributed Agent-BasedSimulations, 20th European Modeling and Simulation Symposium, September 2008, Briatico, Italy, 2008 (in press)Professor Bert SakmannProfessor of Biomedical SciencesThe appointment of the Nobel Prize-winning scientist, Professor Bert Sakmann, in 2007 was hailed as a coup forthe University of Ulster and further recognition of its continued emphasis and commitment to research excellence.Professor Sakmann was awarded the 1991 Nobel Prize for Physiology, with his research partner Erwin Neher, fortheir discoveries ‘concerning the function of single ion channels in cells’.Professor Sakmann is leading a pioneering research project into the nature of nerve cells, the main aim of which isto learn more about how the brain processes information. This project is being conducted by Professor Sakmann’sNeurobiology laboratory at the Max Planck Institute (Munich) in conjunction with the Biomedical Sciences ResearchInstitute (BMSRI) and other major research centres. Researchers within the BMSRI, led by Dr Kurt Saetzler, havedeveloped software that will be used to analyse research data arising from this project. It is hoped that the softwareand its 3D imaging facility developed at Ulster will help identify “building blocks” that influence brain mechanisms thatenable us to make decisions, to learn and to memorise and this should provide even deeper insights into patterns inhuman brain activity.Professor Sakmann delivered a special public lecture entitled: ”Decision-making: anatomy and physiology in the cerebralcortex”, at the Coleraine campus in October 2008 to mark his tenure as Professor of Biomedical Sciences atUlster.Professor Sakmann is interested in using computerised or so-called in silico models to simulate how neuronscommunicate with each other. This will contribute significantly to our future understanding on how we thinkand memorise and is at the forefront of international research in Neuroscience as documented by below list ofpublications.100

Publications:Frick A, Feldmeyer D, Sakmann B; Postnatal development of synaptic transmission in local networks of L5A pyramidalneurons in rat somatosensory cortex; Journal of Physiology, 585: 103-116, 2007Helmstaedter M, de Kock CP, Feldmeyer D, Bruno RM, Sakmann B; Reconstruction of an average cortical column insilico; Brain Research Reviews, 55: 193-203, 2007Kerr JN, de Kock CP, Greenberg DS, Bruno RM, Sakmann B, Helmchen F; Spatial organization of neuronal populationresponses in layer 2/3 of rat barrel cortex; Journal of Neuroscience, 27:13316-13328, 2007Krieger P, Kuner T, Sakmann B; Synaptic connections between layer 5B pyramidal neurons in mouse somatosensorycortex are independent of apical dendrite bundling; Journal of Neuroscience, 27: 11473-11482, 2007Larkum ME, Waters J, Sakmann B, Helmchen F; Dendritic spikes in apical dendrites of neocortical layer 2/3 pyramidalneurons; Journal of Neuroscience, 27: 8999-9008, 2007Oberlaender M, Bruno RM, Sakmann B, Broser PJ; Transmitted light brightfield mosaic microscopy for three-dimensionaltracing of single neuron morphology; Journal of Biomedical Optics, 12: 064029, 2007Sarid L, Bruno R, Sakmann B, Segev I, Feldmeyer D; Modeling a layer 4-to-layer 2/3 module of a single column in ratneocortex: interweaving in vitro and in vivo experimental observations; Proceedings of the National Academy of Sciences(USA), 104: 16353-16358, 2007Tan HO, Reid CA, Single FN, Davies PJ, Chiu C, Murphy S, Clarke AL, Dibbens L, Krestel H, Mulley JC, Jones MV,Seeburg PH, Sakmann B, Berkovic SF, Sprengel R, Petrou S; Reduced cortical inhibition in a mouse model of familialchildhood absence epilepsy; Proceedings of the National Academy of Sciences (USA), 104: 17536-17541, 2007Broser P, Grinevich V, Osten P, Sakmann B, Wallace DJ; Critical period plasticity of axonal arbors of layer 2/3 pyramidalneurons in rat somatosensory cortex: layer-specific reduction of projections into deprived cortical columns;Cereb Cortex, 18: 1588-1603, 2008Broser PJ, Erdogan S, Grinevich V, Osten P, Sakmann B, Wallace DJ; Automated axon length quantification for populationsof labelled neurons; Journal of Neurosci Methods, 169: 43-54, 2008de Kock CP, Sakmann B; High frequency action potential bursts (>or= 100 Hz) in L2/3 and L5B thick tufted neuronsin anaesthetized and awake rat primary somatosensory cortex; Journal of Physiology, 586: 3353-3364, 2008Frick A, Feldmeyer D, Helmstaedter M, Sakmann B; Monosynaptic connections between pairs of L5A pyramidalneurons in columns of juvenile rat somatosensory cortex; Cereb Cortex, 18:397-406, 2008Voigts J, Sakmann B, Celikel T; Unsupervised whisker tracking in unrestrained behaving animals; Journal of Neurophysiology,100: 504-515, 2008Wallace DJ, Sakmann B; Plasticity of representational maps in somatosensory cortex observed by in vivo voltagesensitivedye imaging; Cereb Cortex, 18: 1361-1373, 2008101

Dr Daniel BerrarLecturer in Biomedical SciencesBrief biography:Dr Daniel Berrar studied Medical Informatics at the University of Applied Sciences of Heilbronn (Germany), theUniversity of Heidelberg (Germany), and the University of Montreal (Canada). He received the BSc in MedicalInformatics from the University of Heidelberg in 1996 and the MSc in 1999. From July 2000 to January 2002, he wasconducting research in the Intelligent Bioinformatics Systems Group at the German Cancer Research Center inHeidelberg. In February 2002, he joined the Systems Biology Research Group at the School of Biomedical Sciences,Faculty of Life and Health Science, at the University of Ulster at Coleraine, Northern Ireland. He completed his Ph.D.in Bioinformatics in October 2004. From 2005 to 2007, Daniel Berrar worked as research fellow in the SystemsBiology Research Group at the University of Ulster. Since July 2007, he is lecturer in Biomedical Sciences at theUniversity of Ulster. In August 2008, Daniel was awarded a research fellowship by the Japanese Society for thePromotion of Science to conduct collaborative research from November 2008 to November 2010 with Dr HiroakiKitano at the Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo.Main research activities in the period:• Research in the investigated areas.• Preparation, publication and presentation of research results.• Preparation of new research grant proposals.• Co-supervision of one PhD student.• Member of editorial board of one international journal.• Membership of four international program committees (IPC): CAMDA07, IDA07, IFIP AI08, DMIN08.• Networking with research institutes in the UK and Japan.• Design of module “Introduction to Statistics and Genomic Data Analysis using R” (BMS860).• Referee for 12 journals and 4 conferences.Dr Berrar is the named inventor for two patents filed during the reporting period:• United Kingdom Patent Application No. 0724131.8: Use of KIR genes for predicting response to therapy• United Kingdom Patent Application, No. 0821787.9: A genomic-based method of stratifying breast cancerpatients.Publications:Graham JE, Berrar D, McGilligan VE, Leccisotti A, Moore JE, Bron AJ, and Moore TCB; Attitudes towards diagnostictests and therapies for dry eye disease; Ophthalmic Research, accepted (2008)McCann MJ, Gill CI, Linton T, Berrar D, McGlynn H, Rowland IR; Enterolactone restricts the proliferation of theLNCaP human prostate cancer cell line in vitro; Mol Nutr Food Res, 52: 567-580, 2008Dr Chin-Kuo ChangLecturer in BiostatisticsDuring the period, Dr Chang’s study was accepted for presentation by poster in the annual meeting of AmericanSociety of Epidemiologic Research in Chicago in June with the abstract published in AJE:102

Publication:Chang CK, Tseng KC, Lai NS, and Chou AL; Prognostic factors of chronic hepatitis C patients treated by pegylatedinterferon-alfa plus Ribavirin in Taiwan; American Journal of Epidemiology, 167: S73, 2008Dr Kurt SaetzlerLecturer in Computational BiologyContact details:T: +44 (0)28 70324021k.saetzler@ulster.ac.ukDr Kurt Saetzler’s main research interest is in spatial modelling of biological systems and digital image processing.Below find a list of projects and international project partners with whom he is networking and cooperating with:Spatial Systems Biology: coordinator of a COST network application involving several sites across Europe.3-D reconstructions from synaptic morphologies using serial electron-microscopical ultrathin sections: this is in collaborationwith: Professor Bert Sakmann (Max Planck Institute for Neurobiology, Munich), Michael Frotscher (University ofFreiburg), Joachim Luebke (Research Centre Juelich), Dr Arnd Roth and Professor Michael Haeusser (UCL). Thiswork also involves the coordination and development as part of the OpenCAR reconstruction project (opencar.ulster.ac.uk).Spatio-temporal simulations of synaptic transmission: a European network interested in the simulation of synaptictransmission has been formed (Professor Michael Haeusser, Dr Arnd Roth (UCL), Professor Jean-Daniel Boissonnatand Dr Mariette Yvinec (INRIA), Professor Peter Bastian, Dr Stefan Lang (University of Stuttgart), Dr MarkusKirkilionis (Warwick)). A European grant application is still pending.Tracing of stained neurons in SBFSEM series: novel algorithms have been developed as part of a collaboration with theMax Planck Institute for Medical Research in Heidelberg (Professors Winfried Denk and Bert Sakmann and Dr RandyBruno).The overarching topic, systems biology, which tries to integrate in-vivo and/or in-vitro experiments with in-silicomathematical models is at the core of the Life Science Interface between the BBSRC and the EPSRC in the UK. It isalso seen as strategically important to increase the competitiveness of European Science world- wide.Abstracts for conference presentations/posters:Rollenhagen et al. Structural determinants of transmission and plasticity of input synapses on layer 5 pyramidalneurons. Neuroscience Meeting 2007, Abstract and Slide Presentation, Session Number 656.3.Frotscher et al. Fine structure of mossy fiber synapses in the hippocampus revealed by high pressure freezing andfreeze substitution. Neuroscience Meeting 2007, Abstract and Slide Presentation, Session Number 656.7.Saetzler et al. The effects of non-rigid alignments on 3d reconstructions and quantitative measurements in largeseries of electron microscopical ultra-thin sections. Neuroscience Meeting 2007, Abstract, Session Number 104.23/BBB22.Publications:Morrow P and Saetzler K; Validation of in vivo Leukocyte Velocity Estimates via Modeling and Simulation; ConferenceRecord of the Forty-First Asilomar Conference on Signals, Systems and Computers, ACSSC 2007, 1288-1292, 2007Rollenhagen et al. Structural Determinants of Transmission at Large Hippocampal Mossy Fiber Synapses; Journal ofNeuroscience, 27: 10434-10444, 2007103

Zhang et al; Incorporating Feature Based Priors into the Geodesic Active Contour Model and its Application inBiomedical Imagery; Machine Vision and Image Processing Conference, IMVIP ’07, International, 67-74, 2007Guerreiro-Lucas LA, Pop SR, Machado MJ, Ma YL, Waters SL, Richardson G, Saetzler K, Jensen OE, Mitchell CA;Experimental and theoretical modelling of blind-ended vessels within a developing angiogenic plexus; MicrovascularResearch, 76: 161-168, 2008Ma Y-L and Saetzler K; A parallelized surface extraction algorithm for large binary image data sets based on an adaptive3-D Delaunay subdivision strategy; IEEE Transactions on Visualization and Computer Graphics, 14, 160–172, 2008Dr Martin SwainResearch Fellow in BioinformaticsContact details:T: +44 (0)28 70323367mt.swain@ulster.ac.ukDr Swain’s research activities during the reporting period have been mainly focussed on the QosCosGrid Project. Thishas included ongoing development work on a number of use-cases, including topology discovery for gene regulatorynetworks, simulations of the cell membrane, and the development of an evolutionary algorithm toolbox. Duringthis time he has been developing software using ProActive Java and QosCosGrid’s OpenMPI, as well as performingsystem administration tasks on the computational resources that we have contributed to the project’s test-bed.Highlights of this work include:• Presenting a talk on “Reverse Engineering Gene Regulatory Networks” at the Systems Biology RegionalNetwork meeting in Donegal, September 2007.• Attending QosCosGrid meetings in Amsterdam, Barcelona, and Haifa: presented results from our ownresearch and participating in discussions related to project development. Attended the Project Review inBrussels, Oct 2007.• Presenting two papers at the international Conference on Computational Science, June 23-25 th ,Krakow, Poland.• Visiting the University of Coimbra, Portugal for 1 week and gave an invited talk on “Grid Solutions for theP-found Repository of Protein Folding and Unfolding Simulations”, November 2007.• Visiting the University of Queensland for 2 weeks to collaborate on the QosCosGrid project. I also gave aninvited talk on “Distributed Data Grid Solutions for Repositories of Protein Folding and Unfolding Solutions”, July2008.Dr Swain is Member of the Programming Committee for the Barcelona School on Biomedical Informatics that isbeing planned for February 2009.Publications:Hudson BD, Whitley DC, Ford MG, Swain M and Essex JW; Pattern recognition based on color-coded quantummechanical surfaces for molecular alignment; Journal of Mol Model, 14: 49-57, 2008Kravtsov V, Swain M, Dubin U, Dubitzky W & Schuster A; A Fast and Efficient Algorithm for Topology-AwareCoallocation, in Proceedings of the International Conference on Computational Science, Krakow, Poland, 274-283, 2008Kravtsov V, Swain M, Schuster A, Dubitzky W and Dubin U; Grid computing solutions for distributed repositories ofprotein folding and unfolding simulations, in Proceedings of the International Conference on Computational Science (ICCS2008), Poland, 274-283, 2008104

Silva CG, Brito J, Swain M, Dubitzky W and Brito RMM; P-found GRID: A distributed repository for protein folding andunfolding simulations; The Protein Folding and Unfolding Simulation Repository, IBERGRID, May 12-14, Porto, 2008Stankovski V, Swain M, Kravtsov V, Niessen T, Wegener D, Röhm M, Trnkoczy J, May M, Franke J, Schuster A & DubitzkyW; Digging Deep into the Data Mine with DataMiningGrid; IEEE Internet Computing, 12: 69-76, 2008Stankovski V, Swain M, Kravtsov V, Niessen T, Wegener D, Kindermann J & Dubitzky W; Grid-enabling data miningapplications with DataMiningGrid: An architectural perspective; Future Generation Computer Systems, 24: 259–279,2008Swain M, Mandel JJ and Dubitzky W; Comparing Grid Computing Solutions for Reverse-Engineering Gene RegulatoryNetworks, in Proceedings of the International Conference on Computational Science (ICCS 2008), Poland, 106-115, 2008Swain M, Ostropytskyy V, Silva CG, Stahl F, Riche O, Brito RMM, Dubitzky W; Grid Computing Solutions for DistributedRepositories of Protein Folding and Unfolding Simulations; Proceedings of the International Conference on ComputationalScience (ICCS 2008), Krakow, Poland, 70-79, 2008Swain M and Chue Hong N P; Data pre-processing using OGSA-DAI; Book chapter in Data Mining Techniques in GridComputing Environments, Wiley, 2008Vitaliy OstropytskyyResearch AssociateVitaliy Ostropytskyy has been mostly focussed on the European FP6 Chemomentum project during this period.Chemomentum is aimed at developing new ICT in the context of in the context of the European regulatory initiative“Registration and Evaluation of Chemicals” (REACH), promoting the REACH initiative aimed at reducing animaltesting, by developing in silico, grid-based tools. His activities included ongoing development on distributed datamanagement and ontology management of the Chemomentum system. He has been developing software usingJava and Maven tool; and also performing system administration tasks, integrating dedicated server to the sharedChemomentum project’s test-bed.Some of Vitaliy’s work focussed on the Protein Folding and Unfolding Data repository; the system facilitates thesharing of simulation data created by molecular dynamics protein unfolding simulations. The early prototype of thesystem has been updated based on the feedback from the corresponding research community. The repository ispopulated with protein folding and unfolding simulations in order to perform data mining procedures.Some highlights of his work in the reporting period include:• Presenting a talk on “Chemomentum Project - Data Management” at the “European Software, Services and GridTechnology Days”, September 2007, Brussels.• Attending European FP6 Chemomentum project meetings in Juelich (Germany), Milan (Italy), Tartu (Estonia),Dresden (Germany): presented results from our Working Package research and participating in discussionsrelated to project development.• Visiting the Technical University of Dresden (Germany) for 1 week to collaborate on the Chemomentumproject.Vitaliy is Member of the Technical Group 5 of Grid related IST projects, created at the European Grid TechnologyDays 2007.Publications:Swain M, Ostropytskyy V, Silva CG, Stahl F, Riche O, Brito RMM, Dubitzky W; Grid Computing Solutions for DistributedRepositories of Protein Folding and Unfolding Simulations; Proceedings of the International Conference on ComputationalScience (ICCS 2008), Krakow, Poland, 70-79, 2008105

Bala P, Baldridge K, Benfenati E, Casalegno M, Maran U, Miroslaw L, Ostropytskyy V, Rasch K, Sild S, Schöne R and WilliamsN; Handbook of Research on Computational GRID Technologies for Life Sciences, Biomedicine and Healthcare,Editor: M. Cannataro, Chapter Title: UNICORE – a middleware for Life Sciences Grids, 2008 (to appear)Schöne R, Rasch K, Ostropytskyy V, Mix H, Romberg M; The Chemomentum Data Services - A flexible Solution forData Handling in UNICORE Proceedings of 4th UNICORE Summit 2008, Springer LNCS, Euro-Par 2008 Workshopproceedings (to appear)106

12. VISION SCIENCES RESEARCH GROUPRESEARCH STRATEGYThe Vision Science Research Group (VSRG) conducts investigations on the entire visual system, from the opticalelements of the eye: the cornea and lens to the retina and higher visual pathways. The underlying strategy is to studythe structural and functional aspects of the ocular elements and visual system and how these are applied to the studyof developmental, growth and ageing processes. The main research themes in the group can be divided into clinicaland basic (laboratory) science:Laboratory Sciences:Optics: the optics of the lens and cornea are studied using ray tracing analysis, aberrometry, optical coherencetomography to determine changes with ageing, as the eye focuses and after refractive surgery.Biomechanics//Finite Element Analysis: the elasticity of the cornea and sclera is being measured by modelling the eyeballas a pressure vessel. Finite element analysis is used to model the optical/mechanical processes to determine howmechanical properties can impact on optical quality.Biochemistry/Cell biology: the protein chemistry of the eye lens is being studied to determine how the proteindistributions are linked to refractive index of the lens and cell culture techniques are used to look at damage toDNA in the cells from optical elements of the eye.Immunology: Immunological work had involved investigations of the ocular surface using patient samples, ocular surfacecells and donor tissue to identify biomarkers for application in translational patient based research which involvesdiagnostic and therapeutic approaches. Present research concentrates on two ocular surface conditions: HerpesSimplex Virus infection of the ocular surface and dry eye.Psychophysics: Psychophysical studies are being used to study the higher visual pathways as well as applied toinvestigations of age-related disease conditions such as glaucoma.Imaging: This work is conducted in collaboration with colleagues from Computing and Engineering and encompassesprojects on iris imaging to determine immutable features for biometric identification as well as retinal imaging forimproved diagnosis of eye disease.Clinical Sciences:Paediatric vision/epidemiological studies: Refractive errors in Northern Irish schoolchildren are being investigated in amajor epidemiological study that is the first of its kind.Developmental anomalies: Studies are being conducted on the ocular and optical anomalies in Downs syndrome andin Albinism.Geriatric/low vision: The association between ageing and eye disease is well known and these studies include work onmacular degeneration, glaucoma and the ocular effects of Alzheimer’s disease.Sports Vision: investigations are concerned with the effect of binocular vision on sports performance and how this canbe improved in a variety of different sports.Dyslexia: the effects of contrast and colour on reading, writing and learning ability are being investigated to comparevalidity of analytical methods and to determine the best methods of analysis, diagnosis and treatment for the childrenand adults who present with reading and writing difficulties.107

In addition there is a growing theme in healthcare ethics and medical law as applied to eye care practice. The mainareas of research are Gillick competency and presumed consent.108

MEMBERS OF THE GROUP:Academic StaffProfessor Barbara Pierscionek, Group LeaderProfessor of Optometry & Vision ScienceContact details:T: +44 (0)28 70323293b.pierscionek@ulster.ac.ukProfessor Pierscionek works on the all aspects of the anterior eye involving a range of biochemical and biophysicalmethods.The optics of the lens and cornea have been studied using ray tracing and mathematical analysis (Eikonal equation) todetermine the refractive indices of these elements and how these varies across species and with age and development.The optics of the eye is dependent on its rheological (biomechanical properties) and Professor Pierscionek, incollaboration with Dr Widlicka from the Wroclaw University of Technology have developed a means of measuringthe elastic properties of the cornea and sclera in an intact eyeball. Elasticity of the lens is being modelled using FiniteElement Analysis and based on experimental results from simulations of lens shape change (as it occurs in the eye).The link between optics and mechanics of the eye and how these alter with age, disease and surgery is a new field ofresearch which will be increasingly important as a national and international priority given the ageing population andthe growing demand for refractive surgery.Finite element lens:The functional (optical and mechanical) features are being studied in parallel with structural investigations of lensprotein distributions and how these change with growth and ageing in a variety of species. This work has resulted inestablishing collaborations with Professor Michael Dunn and Dr Giuliano Elia from the Conway Institute in Dublin.The biochemical work also involves cell culture and investigations of the viability of DNA and chromosomal damagein response to chemical agents and quantum dots. This work is conducted in collaboration with Dr Wei Chen fromthe University of Texas in Arlington and with Dr Ronald Schachar from Pfizer. It will also involve collaborations withProfessors McLaughlin and Meenan from the Nanotechnology Research Institute. This work is aimed at having afuture impact on better understanding the structure/function relationships of the anterior eye structures and howthese alter with age and disease.Cell CulturesIn addition, Professor Pierscionek is investigating iris biometry in collaboration with Professor Scotney and Dr Morrowfrom Computing and Engineering to design improved methods of identification. This addresses the internationalpriority in the biometrics as applied to issues of security, both national and international.109

Clinical work involves development of sports vision as a research theme and to see how binocular vision processescan be optimised to improve sports performance as well as reading and writing ability. This work is conducted withDr McDowell and Mr Gilsenan (private practice) and resulted in a television interviewed on 9th January 2008. Theimprovement of reading writing and sporting ability addresses national and international priorities in education andlearning.Professor Pierscionek utilises her legal qualifications to develop research in healthcare ethics and medical law asapplied to eye care practice. This has produced the first book of its kind on healthcare ethics and law for eye carepractice and a peer-review paper which from its publication in April to July 2008 had been accessed over 1465 timesand remains one of the top 10 most viewed articles in BMC Medical Ethics.Professor Pierscionek was invited to give a plenary lecture: “The paradox of the eye lens”, SPIE Student ChapterWroclaw, Poland (May 2008)During the year Professor Pierscionek also secured a DEL-funded studentship for “Identification of Iris Biometrics”(circa £48,000).Publications:Asejczyk-Widlicka M and Pierscionek BK; Fluctuations in intraocular pressure and the potential effect on aberrationsof the eye; British Journal of Ophthalmology, 91: 1054-1058, 2007Belaidi A and Pierscionek BK; Modelling internal stress distributions in the human lens: can opponent theoriescoexist? Journal of Vision, 7: 1-12, 2007Schachar RA, Kamangar F and Pierscionek BK; Edinger-Westphal and pharmacologically stimulated accommodativerefractive changes and lens ciliary process movements in rhesus monkeys; by L.A. Ostrin and A. Glasser; ExperimentalEye Research, 85: 298-301, 2007Keenan J, Orr DF and Pierscionek BK; Patterns of protein distribution in porcine eye lenses; Molecular Vision, 14: 1245-1253, 2008Pierscionek BK; What is presumed when we presume consent? BMC Medical Ethics, 9:8 doi:10.1186/1472-6939-9-8,2008Schachar RA, Chen W, Woo BK, Pierscionek BK, Zhang X and Ma L; Diffusion of nanoparticles into the capsule andcortex of the crystalline lens; Nanotechnology, 19: 1-4, 2008Schachar RA, Kamangar F and Pierscionek BK; Changes in lens dimensions and refractive index with age andaccommodation; Optometry and Vision Science, 85: 281-282, 2008Siedlecki D, Kasprzak H and Pierscionek BK; Radial gradient index intraocular lens: a theoretical model; Journal ofModern Optics, 55: 639-647, 2008Book:Pierscionek BK; Law and ethics for the eye-care professional; Elsevier (2008)110

Professor Roger AndersonProfessor of Vision ScienceContact details:T: +44 (0)28 70324891rs.anderson@ulster.ac.ukProfessor Anderson’s research interests centre around non-invasive assessment of the visual system using chromaticand achromatic measures of spatial acuity and the relationship between structural and functional measures of visualintegrity.The separation of neural and optical limits to both central and peripheral vision is also a major area of interest. Thishas particular clinical application in eye conditions such as glaucoma, age-related macular degeneration and in theageing eye where different visual functions may be selectively affected and neural damage must be separated from thefiltering effects of the eye’s optics. This work is being undertaken in collaboration with Moorfields Eye Hospital andthe UCL Institute of Ophthalmology in London where Professor Anderson is also Principal Optometrist (Research)and Professor of Visual Neuroscience respectively.Scanning laser image of optic nerve head.Professor Anderson’s recent work has increasingly involved the application of novel imaging methods to assessretinal structure and integrity in conditions that affect the photoreceptors of the retina, e.g. age-related maculardegeneration, retinitis pigmentosa and myopia. Current methods to grade retinal appearance in conditions suchas age-related macular degeneration do not relate well to the actual visual performance of the patient. A modifiedscanning laser ophthalmoscope, producing high magnification scans of the photoreceptor layer allows us to imagethe retinal cones in vivo. This may provide us with a better method to grade retinal structural change based onphotoreceptor loss.In vivo image of retinal conesProfessor Anderson continues his work as a member of the MRC College of Experts, the Royal Irish Academy LifeScience Committee, the General Optical Council Education Committee and the College of Optometrists ResearchCommittee.111

In 2009 he was appointed Chairman of the Education Committee of the European Council for Optometry and Optics(ECOO) and a member of the ECOO Executive Committee.Publications:Hogg RE, Stevenson MR, Chakravarthy U, Beirne RO, Anderson RS; Early features of AMD; Ophthalmology, 114:1028-1028e3, 2007Hogg RE, Anderson RS, Stevenson MR, Zlatkova MB, Chakravarthy U; In vivo macular pigment measurements.A comparison of Resonance Raman Spectroscopy and Heterochromatic Flicker Photometry; British Journal ofOphthalmology, 91: 485-490, 2007Anderson RS, Redmond T, McDowell DR, Dempsey KMM, Zlatkova MB; The robustness of various forms of perimetryto different levels of induced intraocular straylight; Invest Ophthalmol Vis Sci. (Epub ahead of print).Wolsley CJ, Silvestri G, O'Neill J, Saunders KJ, Anderson RS; The association between multifocal electroretinogramsand OCT retinal thickness in retinitis pigmentosa patients with good visual acuity; Eye, 2008 Oct 31 (Epub ahead ofprint)Beirne RO, Zlatkova MB, Chang CK, Chakravarthy U, Anderson RS; How does the short-wavelength-sensitive contrastsensitivity function for detection and resolution change with age in the periphery? Vision Research, 48: 1894-1901,2008Wolsley CJ, Saunders KJ, Silvestri G, Anderson RS; Investigation of Changes in the Myopic Retina using MultifocalElectroretinograms, Optical Coherence Tomography and Peripheral Resolution; Vision Research, 48: 1554-1561, 2008Zlatkova MB, Vassilev A, Anderson RS; Resolution acuity for equiluminant gratings of S-cone positive or negativecontrast in human vision; Journal of Vision, 8: 9.1-10 2008Dr Tara MooreSenior Lecturer in ImmunologyContact details:T: +44 (0)28 70324577t.moore@ulster.ac.ukDr Tara Moore’s research investigates the immunology of the ocular surface using patient samples, ocular surfacecells and donor tissue to identify biomarkers for application in translational patient based research, which involvesdiagnostic and therapeutic approaches. The translational research is greatly facilitated through close collaborativework with Consultant Ophthalmic Surgeons within the Belfast Health and Social Care Trust, Italy, Birmingham andMoorfields Eye clinic. Presently research concentrates on two ocular surface conditions: Herpes Simplex Virusinfection of the ocular surface and dry eye and it is funded primarily by the HPSS Research and Development Officeand Invest NI.Dr Moore works closely with other ocular immunology researchers within the Centre for Molecular Biosciences,which include: Mr Johnny Moore, Consultant Ophthalmologist and Visiting Professor, Dr Jo Graham, Post doctoralResearch Associate, Dr Elena Novitskya, Post doctoral Research Associate and Ophthalmologist, Dr Vicky McGilligan,Post doctoral Research Associate and Visiting Lecturer. Research interests focus on the microbiology of the ocularsurface and the associated immunological responses. Dr Moore’s research investigates the immunology of theocular surface using patient samples, ocular surface cells and donor tissue to identify biomarkers for application intranslational patient based research which involves diagnostic and therapeutic approaches.112

The translational research is greatly facilitated through close collaborative work with Consultant OphthalmicSurgeons within the Belfast Health and Social Care Trust, Italy, Birmingham and Moorfields Eye Hospital.Presently research concentrates on two ocular surface conditions: Herpes Simplex Virus infection of the ocularsurface and dry eye and it is funded primarily by the HPSS Research and Development Office and Invest NI. Herpessimplex virus type 1 (HSV-1) infections are amongst the most common clinically encountered infections in ophthalmicpractice. In particular, Herpes Simplex Keratitis (HSK) is a sight threatening ocular infection requiring a specific andprompt diagnosis. Correct diagnosis of HSK is critically important for appropriate patient management. The DryEye research includes clinical trials for new therapeutics and assessment of diagnostic assays for DE. Ultimately theresearch by Dr Moore and her team aims to deliver a personalised approach to the management of ocular surfaceproblems in the patient.Dr Moore was awarded a distinguished research fellowship award by the University of Ulster in December 2007for her sustained efforts in vision science research. She has developed worthwhile collaborations with centres ofexcellence nationally and internationally; published papers in some of the top journals and gained funding for herhighly innovative work.Publications:Cathcart M, McGrath P, Goodall EA & Moore CBT; An investigation of the interface between the Office of the PoliceOmbudsman for Northern Ireland and Forensic Physicians in Northern Ireland; Medicine Science and the Law, 8: 117-123, 2007Graham JE, Moore JE, Jiru X, Moore JE, Goodall EA, Dooley JSG, Hayes V, Dartt DA, Downes SC & Moore CBT;Ocular Pathogen or Commensal: A PCR Based Study of Surface Bacterial Flora in Normal and Dry Eyes; InvestigativeOphthalmology & Visual Science, 48: 5616-5623, 2007Novitskaya ES, Dean SJ, Moore JE, Sharma A; A novel method to study fluorescein staining of the ocular surface usingthe fluorescein angiogram setting of the fundus camera; Cont Lens Anterior Eye, 30: 258-259, 2007Atkinson SD, Moore JE, Shah S, Sharma S, Best RM, Leccisotti A, Alarbi M, Rimmer D, Gardiner T, Moore CBT; P63expression in conjunctival proliferative diseases: pterygium and LOC syndrome; Current Eye Research, 33: 551-558,2008Burns A, Goodall E, Moore CBT; A study of suicides in Londonderry, Northern Ireland, for the year period spanning2000–2005; Journal of Forensic and Legal Medicine, 15: 148-157, 2008Dean SJ, Novitskaya ES, Moore CBT, Moore JE, Sharma A; Documentation of corneal epithelial defects withfluorescein enhanced digital fundus camera photography; Clinical and Experimental Ophthalmology, 36: 113-118, 2008Graham JE, Moore JE, Moore JE, McClurg B, Moore CBT; Cross contamination of hospital ophthalmic slit lamps byocular bacteria; American Journal of Infection Control, 36: 605-606, 2008Graham JE, Graham RLJ, Beirne R, McGilligan VE, Downes CS, Moore JE, Moore CBT, McMullan G; The use ofconjunctival swab for the proteomic characterisation of Dry Eye Syndrome; Journal of Proteomics and Bioinformatics;1: 20-33, 2008Graham JE, Moore JE, Goodall EA, Dartt DA, Leccisotti A, McGilligan VE, Moore TC; Concordance between commondry eye diagnostic tests; British Journal of Ophthalmology, 2008Hall JA, Goodall E & Moore CBT; Alleged Drug Facilitated Sexual Assault (DFSA) in Northern Ireland from 1999 to2005: A Study of Blood Alcohol Levels; Journal of Forensic and Legal Medicine, 15: 497–504, 2008Hall JA & Moore CBT; A Review of Drug Facilitated Sexual Assault; Journal of Forensic and Legal Medicine, 15: 291-297,2008Novitskaya ES, Moore JE, Athanasiadis Y, Moore CBT, Sharma A; A highly sensitive technique for imaging and effectivemonitoring of staining of the ocular surface defect; Eye, 23: 234-235, 2008113

Stevenson TR, Goodall EA and Moore CBT; A retrospective audit of the extent and nature of domestic violence casesidentified over a three year period in the two District Command Units of the Police Service of Northern Ireland;Journal of Forensic and Legal Medicine, 15: 430–436, 2008Graham JE, Berrar D, McGilligan VE, Leccisotti A, Moore JE, Bron AJ, Moore CBT; Attitudes towards diagnostic testsand therapies for dry eye disease; Ophthalmic Research, 2008 (In press)Novitskaya ES, Moore JE,, Dean SJ, Athanasiadis Y, McGilligan VE, Moore T, Sharma A; Imaging the epithelial defects ofthe ocular surface with digital fundus camera using fluorescein angiography settings; Cornea, 2008 (In press)Professional Publications:Shah S, Leccisotti A, Moore JE, Moore CBT; E-Learning could solve Refractive Surgery Training Dilema. Aiming forWorldwide Excellence in Cataract and Refractive Surgery; Ophthalmology Times Europe, p29-30, 2007Shah S, Moore JE, Leccisotti A, McConville D, Moore CBT; Cataract, Refractive E-Learning Course; Cataract andrefractive surgery today Europe, 3: 83-85, 2008Shah S, McAlinden C, Leccisotti A, Moore JE, McConville D, Moore T; Past and present refractive techniques; Cataractand refractive surgery today Europe, 3: 80-82, 2008Shah S, McAlinden C, Leccisotti A, Moore JE, McConville D, Moore T; Preoperative assessment in refractive surgery;Cataract and refractive surgery today Europe, 3: 76-78, 2008Shah S, McAlinden C, Leccisotti A, Moore JE, McConville D, Moore T; Excimer laser refractive surgery; Cataract andrefractive surgery today Europe, 3: 61-63, 2008Shah S, McAlinden C, Leccisotti A, Moore JE, McConville D, Moore T; Review of two courses: correcting regular andirregular astigmatism, phakic IOLs; Cataract and refractive surgery today Europe, 3: 92-94, 2008Shah S, McAlinden C, Leccisotti A, Moore JE, McConville D, Moore T; Complications of Refractive surgery; Cataractand refractive surgery today Europe (In press)Dr Kathryn SaundersSenior Lecturer in Vision ScienceContact details:T: +44 (0)28 70324433kj.saunders@ulster.ac.ukDr Saunders’ research aims to improve understanding of the developing visual system and to enhance management ofpaediatric visual disorders. Collaboration with health and education professionals, related charities and stakeholdersensures the relevance and impact of this work in clinical service.The work published and ongoing during the period of the annual reporthas provided insight into visual function in the presence of Downsyndrome (the most common genetic cause of learning disability) andmyopia (which affects at least 10% of the population).Publications this year have also addressed clinical protocols used in the assessment of children with neurologicalimpairment; a vulnerable group that is increasing in number in the general population as survival rates of extremelypreterm babies with associated neurological damage improve.114

During the period of the annual report data collection for the externally funded epidemiological study of refractiveerrors in school children in Northern Ireland was completed, and follow-on funding (£50,466) was secured from theCollege of Optometrists. These important studies will provide the first description of refractive error in school agechildren in the UK and Ireland since the 1960’s. These novel data are not only valuable for researchers investigatingthe factors associated with the onset and progression of myopia; a ‘hot topic’ in vision science at present, they willbe an important resource for the eye care professions, the NHS and UK and Irish government agencies. In particularaccruing data may be used to inform decisions about the utility of screening for myopia and in implementing futureservice provision for the visually impaired.Ongoing work to develop further Down syndrome studies and to initiate work on visual development in albinisminvolved new collaborative links with DHSSPS colleagues and resulted in two DEL studentships (‘Ocular aberrationsin Down syndrome’, KJS primary supervisor and ‘Refractive development in Albinism’, KJS second supervisor (both£48,540)) for which students were interviewed and recruited.Dr Saunders is a Member of the Research Committee of the UK College of Optometrists; the Executive Committeeof the NI HPSS R&D Office Recognised Research Group in Vision; and the Executive Committee of the Vision Groupof the Northern Ireland Clinical Research Network.Publications:Little JA, Woodhouse JM, Lauritzen JS, Saunders KJ; The Impact of Optical Factors on Resolution Acuity in Childrenwith Down Syndrome; Investigative Ophthalmology and Visual Science, 48: 3995-4001, 2007McClelland JF, Saunders KJ, Hill N, Magee A, Shannon M, Jackson AJ; The changing visual profile of children attendinga regional specialist school for the visually impaired in Northern Ireland; Ophthalmic and Physiological Optics, 26: 556-560, 2007McCulloch DL, Mackie RT, Dutton GN, Bradnam MS, Day RE, McDaid GJ, Phillips S, Napier A, Herbert AM, SaundersKJ, Shepherd AJ; A visual skills inventory for children with neurological impairments; Developmental Medicine andChild Neurology, 49: 757-763, 2007Saunders, KJ, McClelland JF, Richardson PM, Stevenson M; Clinical Judgement of near pupil responses provides a usefulindicator of ocular accommodation (focusing ability) in children with cerebral palsy; Developmental Medicine andPaediatric Neurology, 50: 33-37, 2008Wolsley CJ, Saunders KJ, Silvestri G, Anderson RS; Investigation of changes in the myopic retina using multifocalelectroretinograms, optical coherence tomography and peripheral resolution acuity; Vision Research, 48:1554-1561, 2008115

Dr Raymond BeirneLecturer in OptometryContact details:T: +44 (0)28 70324477r.beirne@ulster.ac.ukDr Beirne’s research interests are in pure and applied human visual psychophysics, ocular ageing and ocular disease.He has been involved in a variety of laboratory-based and clinical studies of human visual function which havefocused on the normal short-wavelength visual system, how it is affected by age and the changes that can occur inthe ocular diseases of glaucoma and age-related macular degeneration.The Farnsworth-Munsell 100 hue test.In particular, he has examined the structure-function relationship between short-wavelength acuity and the neurallimits to vision imposed by the retinal anatomy. The aims of Dr Beirne’s research are to gain a better understandingof how visual function changes with age, the impact this has on the observer and the effect ocular disease has onvisual function. The ability to develop novel measures of visual function in ocular disease, which better identifydisease and progression earlier than traditional methods is an ultimate goal. Dr Beirne was included in the Universityof Ulster submission to the 2008 Research Assessment Exercise, UoA 12.Publications:Beirne RO, McIlreavy L & Zlatkova MB; The effect of lens yellowing on Farnsworth-Munsell 100 hue error score;Ophthalmic and Physiological Optics, 28: 448-456, 2008Beirne RO, Zlatkova MB, Chang CK, Chakravarthy U & Anderson RS; How does the short-wavelength-sensitivecontrast sensitivity function for detection and resolution change with age in the periphery? Vision Research, 48: 1894-1901, 2008AbstractsBeirn RO, Hogg RE, Stevenson MR, Anderson RS & Chakravarthy U; Visual function, age-related maculopathy stageand the subsequent development of age-related macular degeneration; Investigative Ophthalmology and Visual Science,49: ARVO E- abstract 2894, 2008Beirne RO, McIlreavy L, Gore S & Zlatkova MB; Age-related lens yellowing per se contributes little to the increase inFarnsworth-Munsell 100 hue error scores with age; Ophthalmic and Physiological Optics, 28: 96. 2008116

Dr Jan LauritzenLecturer in OptometryDr Lauritzen’s research focuses on human psychophysics of early visual processes in the retina, primary visual cortexand extrastriate areas, and computer modelling of those processes. In collaborations, Dr Lauritzen also has a widermultidisciplinary interest in computer modelling of physiological processes in general and the design of psychophysicalprotocols for sensory physiology and experimental psychology.Computer modelling:An array of model receptivefields used to represent simplecells in V1The early steps in vision are mediated by cells with relatively simple receptive fieldsthat have been well described. However, computer models using such receptive fieldsnevertheless provide poor predictions of psychophysical performance in tasks thoughtto be mediated exclusively or predominantly in the retina and primary visual cortex (V1),especially when the test image is complex, such as a natural image. Computer modellingof the connections between cells in V1 involved in contrast gain control mechanisms andresponses from outside the classical receptive field has been used to improve predictionof psychophysical results in contrast discrimination tasks involving natural images.A similar computer model has also been used to demonstrate that contrast gain controlcan adequately account for differences in the contrast in natural images produced bydifferent lighting conditions (diffuse and direct), thus providing a form of ‘contrastconstancy’.Example of an image pair of foliage taken in direct light (left) and diffuse illumination (right). A model of contrastnormalisation virtually eliminates the differences between the two images.Human psychophysicsContrast discrimination tasks, where human observers are detect a simple contrast stimulus before a maskingbackground, provide well-understood, predictable thresholds when the mask is also simple. However as the maskbecomes more complex, thresholds become rapidly less predictable, and for natural or pseudo-natural images resultscan be counter-intuitive. For example, masking experiments on natural images have shown that, when an image isfiltered to remove the contrast that should optimally mask a particular contrast channel, thresholds often increase(i.e. the task becomes harder). Intracortical interactions are thought responsible, and computer models are beingused to determine the nature of these interactions, in view of predicting psychophysical thresholds correctly fordifferent types of stimuli with a single model.117

Dr Julie McClellandLecturer in OptometryOngoing research during this reporting period has continued to investigate visual function in children with neurologicalimpairment (cerebral palsy). This research, which maintains collaborations with the Belfast Health and Social CareTrust, aims to improve the understanding of visual development in this population. A publication stemming from theCP research describes the use of a clinical tool to identify visual anomalies in this vulnerable group.Work describing the changing visual profile over a 30-year period of children attending a school for those with visualimpairment in Northern Ireland was published during this period. It highlights the increasing numbers of childrenwith visual impairment and additional difficulties attending this specialist school and describes the changing origins ofthe visual impairment over the previous 30 years.A PhD examining visual function in a group of children with reading difficulties will provide novel data from aEuropean population and will strengthen collaborations with clinical optometrists in Europe.Data collection for an epidemiological study of refractive error in Northern Ireland school age children has recentlybeen completed. This study investigated the prevalence and degree of refractive anomalies and associated riskfactors in a UK population.Funding was secured for a study to investigate the incidence and nature of refractive anomalies in children withalbinism. This population-based study will describe the visual profile of this particular group providing previouslyunavailable data. A PhD student has been recruited to the project.Publications:McClelland JF, Saunders KJ, Hill N, Magee A, Shannon M, Jackson AJ; The changing visual profile of children attendinga regional specialist school for the visually impaired in Northern Ireland; Ophthalmic and Physiological Optics, 26: 556-560, 2007Saunders KJ, McClelland JF, Richardson PM, Stevenson M; Clinical Judgement of near pupil responses provides a usefulindicator of ocular accommodation (focusing ability) in children with cerebral palsy; Developmental Medicine and ChildNeurology, 50: 33-37, 2008Mr Johnny Moore, ConsultantOphthalmologistVisiting ProfessorMr Johnny Moore, Visiting Professor with University of Ulster works closely with other ocular immunology researcherswithin the Centre for Molecular Biosciences, which include: Dr Tara Moore, Senior Lecturer, Dr Jo Graham, Postdoctoral Research Associate, Dr Elena Novitskaya, Post doctoral Research Associate and Ophthalmologist, Dr VickyMcGilligan, Post doctoral Research Associate and Visiting Lecturer. Mr Moore facilitates and promotes translational118

patient based research within the laboratory. Research interests focus in particular on diagnostic and therapeuticapproaches for the ocular surfce.ggFigure 1: This method known as impression cytology provides a flat mount of cells with well-preserved morphology often usedfor further assessment via real time PCR for detection of viral antigen or bacterial DNA or immunofluorescent detection ofviral antigen.The two common conditions which are investigated are Herpes Simplex Keratitis and Dry Eye. Herpes SimplexKeratitis (HSK) is a sight threatening ocular infection requiring a specific and prompt diagnosis which is caused byHerpes simplex virus type 1 (HSV-1). HSV-1 ocular infections are amongst the most common clinically encounteredinfections in ophthalmic practice. Correct diagnosis of HSK is critically important for appropriate patient managementand research within the group to date has focused on a fluorescein conjugated monoclonal antibody assay and nestedreal time PCR assay as diagnostic tools for HSK.Dry Eye research to date within the group has involved over 200 subjects and has investigated the microbiology ofthe ocular surface in terms of bacteria present and their impact on the cells of the ocular surface. Additional patientbased research includes: concordance between common dry eye diagnostic tests and attitudes towards diagnostictests and therapies for dry eye disease. All research efforts are within the area of personalised medicine for bothdiagnostics and therapeutic ocular pathology.External Research Grants (J Moore)Dr Tara Moore, Dr Victoria McGilligan, Prof Jonathan Moore, POC: Ocular Surface, Diagnostic tool, Invest NorthernIreland, £73,707Dr Victoria McGilligan, Prof Jonathan Moore, Dr Tara Moore, TRB Chemedica International SA, Dry Eye Trial,£25,000Dr Tara Moore, Dr Victoria McGilligan, Prof Jonathan Moore, Efficacy of a point of care diagnostic test to rapidly andaccurately diagnose herpes simplex keratitis, HPSS Research and Development Office RRG, £48,676Publications:Graham JE, Moore JE, Jiru X, Moore JE, Goodall EA, Dooley JSG, Hayes V, Dartt DA, Downes SC & Moore CBT;Ocular Pathogen or Commensal: A PCR Based Study of Surface Bacterial Flora in Normal and Dry Eyes; InvestigativeOphthalmology & Visual Science, 48: 5616-5623, 2007Novitskaya ES, Dean SJ, Moore JE, Sharma A; A novel method to study fluorescein staining of the ocular surface usingthe fluorescein angiogram setting of the fundus camera; Cont Lens Anterior Eye, 30: 258-259, 2007Atkinson SD, Moore JE, Shah S, Sharma S, Best RM, Leccisotti A, Alarbi M, Rimmer D, Gardiner T, Moore CBT; P63expression in conjunctival proliferative diseases: pterygium and LOC syndrome; Current Eye Research, 33: 551-558,2008Dean SJ, Novitskaya ES, Moore CBT, Moore JE, Sharma A; Documentation of corneal epithelial defects withfluorescein enhanced digital fundus camera photography; Clinical and Experimental Ophthalmology, 36: 113-118, 2008119

Graham JE, Moore JE, Moore JE, McClurg B, Moore CBT; Cross contamination of hospital ophthalmic slit lamps byocular bacteria; American Journal of Infection Control, 36: 605-606, 2008Graham JE, Graham RLJ, Beirne R, McGilligan VE, Downes CS, Moore JE, Moore CBT, McMullan G; The use ofconjunctival swab for the proteomic characterisation of Dry Eye Syndrome; Journal of Proteomics and Bioinformatics;1: 20-33, 2008Graham JE, Moore JE, Goodall EA, Dartt DA, Leccisotti A, McGilligan VE, Moore TC; Concordance between commondry eye diagnostic tests; British Journal of Ophthalmology, 2008Novitskaya ES, Moore JE, Athanasiadis Y, Moore CBT, Sharma A; A highly sensitive technique for imaging and effectivemonitoring of staining of the ocular surface defect; Eye, 23: 234-235, 2008Graham JE, Berrar D, McGilligan VE, Leccisotti A, Moore JE, Bron AJ, Moore CBT; Attitudes towards diagnostic testsand therapies for dry eye disease; Ophthalmic Research, 2008 (in press)Novitskaya ES, Moore JE, Dean SJ, Athanasiadis Y, McGilligan VE, Moore T, Sharma A; Imaging the epithelial defects ofthe ocular surface with digital fundus camera using fluorescein angiography settings; Cornea, 2008 (in press)Professional Publications:Shah S, Leccisotti A, Moore JE, Moore CBT; E-Learning could solve Refractive Surgery Training Dilema. Aiming forWorldwide Excellence in Cataract and Refractive Surgery; Ophthalmology Times Europe, p29-30, 2007Shah S, Moore JE, Leccisotti A, McConville D, Moore CBT; Cataract, Refractive E-Learning Course; Cataract andrefractive surgery today Europe, 3: 83-85, 2008Shah S, McAlinden C, Leccisotti A, Moore JE, McConville D, Moore T; Past and present refractive techniques; Cataractand refractive surgery today Europe, 3: 80-82, 2008hah S, McAlinden C, Leccisotti A, Moore JE, McConville D, Moore T; Preoperative assessment in refractive surgery;Cataract and refractive surgery today Europe, 3: 76-78, 2008Shah S, McAlinden C, Leccisotti A, Moore JE, McConville D, Moore T; Excimer laser refractive surgery; Cataract andrefractive surgery today Europe, 3: 61-63, 2008Shah S, McAlinden C, Leccisotti A, Moore JE, McConville D, Moore T; Review of two courses: correcting regular andirregular astigmatism, phakic IOLs; Cataract and refractive surgery today Europe, 3: 92-94, 2008Shah S, McAlinden C, Leccisotti A, Moore JE, McConville D, Moore T; Complications of Refractive surgery; Cataractand refractive surgery today Europe (in press)Dr Margarita Vidinova (publishes as Zlatkova)Lecturer in Biomedical SciencesContact details:T: +44 (0)28 70323140mb.vidinova@ulster.ac.ukDr Margarita Vidinova’s research interests focus on non-invasive psychophysical assessment of the retinal mechanismsof visual loss that occurs with age and in glaucoma. The relative contributions of optical and neural factors to thedecrease in visual function with age is also an important area of interest.120

During the period 2007-2008, the changes in spatial summation and resolution acuity with age for both chromatic andachromatic stimuli were investigated in order to reveal the mechanisms of neural loss with age and in glaucoma. Theresults were compared with structural measurements involving novel imaging methods to assess retinal structureand integrity. The work has been undertaken in collaboration with Moorfields Eye Hospital. Studies of Ageing ingeneral and Vision Ageing in particular are among the main national/international research priorities. The resultsof the glaucoma study are already attracting interest from both scientists and clinicians due to the impact that theresearch would have on detection of glaucoma.The results of the above studies were reported at both national and international conferences as listed below:RO Beirne, L McIlreavy, S Gore, MB Zlatkova; Age-related lens yellowing per se contributes little to the increase inFarnsworth-Munsell 100 hue error scores with age; Ophthalmic & Physiological Optics, 2008, 28 (1), p. 96. (BritishCongress for Optometry and Vision Science, University of Ulster, 4-5 September 2007).T Redmond, MB Zlatkova, DF Garway-Heath, RS Anderson; The effect of age on the area of complete spatial summationfor chromatic and achromatic stimuli. Association for Research in Vision and Ophthalmology (ARVO), 5846. April 27-May 1, 2008 (Annual Meeting, Fort Lauderdale, Florida. Electronic Abstract).Publications:Zlatkova MB, Vassilev A, Anderson RS; Resolution acuity for equiluminant gratings of S-cone positive or negativecontrast in human vision; Journal of Vision, 8: 1-10, 2008Beirne RO, Zlatkova MB, Chang C-K, Chakravarthy U, Anderson RS; How does the short-wavelength-sensitivecontrast sensitivity function for detection and resolution change with age in the periphery? Vision Reearch, 48: 1894-190, 2008Beirne RO, McIlreavy L, Zlatkova MB; The effect of age-related lens yellowing on Farnsworth-Munsell 100 hue errorscore; Ophthalmic Physiol Opt., 28: 448-456, 2008121

Research Staff:Dr David OrrSenior Research FellowDr David Orr graduated from Queen’s University Belfast with a BMedSci (2:1 Honours) degree in 1993 andsubsequently with a PhD in 1998. On completing his PhD, he accepted a post at University of Ulster in 1999 andprogressed to his current position as Senior Research Fellow in the Vision Science group. In 2008 he successfullycompleted a Post graduate Certificate in Higher Education Practice, (PgCHEP) specialising in e-learning and researchsupervision practice as well as teaching and learning and has attained the class of Fellow of the Institute of BiomedicalScienceHe has applied his expertise in protein chemistry to studying a variety of diseases: exploring potential moleculartherapeutics for progressive degenerative diseases, including ocular cancers, malignant endocrine cancers anddiabetes, characterising changes in the eye lens. He has identified more than 40 novel human and amphibian peptidesdeposited in Swiss-Prot and EMBL databases and holds a patent on the function of novel peptides entitled “044 InsulinReleasing Peptides”. In 2007 Dr Orr received an International Innovation award jointly funded by the IADR andGlaxoSmithKline (GSK) with Dr Fionnuala Lundy (Queens University) for our project, ‘Characterization of a novelcalcitonin gene-related peptide (CGRP) cleavage enzyme’.”Dr Orr’s expertise in structure-function analysis of peptides and receptor interaction-signalling mechanisms is beingapplied to two current projects on tumour proteomics and biomarker identification of ocular melanomas, (incollaboration with Professor Barbara Pierscionek and the Liverpool Ocular Oncology Centre (LOOC)) andchanges in the distribution of lens crystallin proteins in aging and disease (with Professor Barbara Pierscionek).This work has resulted in several peer reviewed publications and a major collaboration with Professor MikeDunn and Professor Giuliano Elia, Conway Institute, University College Dublin.Size Exclusion Elution Profile proteins in different parts of the porcine lensA. Outer lens B. Inner lens1.200.0301.000.80UA 0.600.400.020UA0.0100.200.000.0002.00 4.00 6.00 8.00 10.00 12.00 14.00 16.00 18.00 20.00Minutes2.00 4.00 6.00 8.00 10.00 12.00 14.00 16.00 18.00 20.00MinutesPublications:Keenan J, Orr DF, Pierscionek BK; Patterns of crystallin distribution in porcine eye lenses; Molecular Vision, 14: 1245-1253, 2008Ikhlas A, Karim El, Linden GJ, Orr DF, Lundy FT; Antimicrobial activity of neuropeptides against a range of microorganismsfrom skin, oral, respiratory and gastrointestinal tract sites; Journal of Neuroimmunol., 200: 11-16, 2008Thompson AH, Bjourson AJ, Orr DF, Shaw C, McClean S; Amphibian skin secretomics: application of parallel quadrupoletime-of-flight mass spectrometry and peptide precursor cDNA cloning to rapidly characterize the skin secretorypeptidome of Phyllomedusa hypochondrialis azurea: discovery of a novel peptide family, the hyposins; Journal ofProteome Research, 6: 3604-3613, 2007Thompson AH, Bjourson AJ, Orr DF, Shaw C, McClean S; A combined mass spectrometric and cDNA sequencingapproach to the isolation and characterization of novel antimicrobial peptides from the skin secretions of Phyllomedusahypochondrialis azurea; Peptides, 28: 1331-1343, 2007122

Dr Joanne GrahamResearch AssociateDr Joanna Graham is a post doctoral research associate in the area of ocular immunology. Dr Graham works with Dr Tara Moore and VisitingProfessor Johnny Moore. Her research focuses on the microbiology of the ocular surface and her work to datefocuses on Dry Eye Syndrome. Dr Graham has assessed various diagnostic tests for Dry Eye, for example usingimpression cytology staining as shown below. Other Dry Eye research involves the molecular analysis of bacteriapresent within conjunctival swabs or impression cytology samples taken from the ocular surface of subjectsFor further information on Dry Eye research carried out by Dr Graham and the team at the University of Ulstersee: http://www.dryeyeni.com/Publications:Graham JE, Moore JE, Jiru X, Moore JE, Goodall EA, Dooley JSG, Hayes V, Dartt DA, Downes SC & Moore CBT;Ocular Pathogen or Commensal: A PCR Based Study of Surface Bacterial Flora in Normal and Dry Eyes; InvestigativeOphthalmology & Visual Science, 48: 5616-5623, 2007Graham JE, Moore JE, Moore JE, McClurg B, Moore CBT; Cross contamination of hospital ophthalmic slit lamps byocular bacteria; American Journal of Infection Control, 36: 605-606, 2008Graham JE, Graham RLJ, Beirne R, McGilligan VE, Downes CS, Moore JE, Moore CBT, McMullan G; The use ofconjunctival swab for the proteomic characterisation of Dry Eye Syndrome; Journal of Proteomics and Bioinformatics;1: 20-33, 2008Graham JE, Moore JE, Goodall EA, Dartt DA, Leccisotti A, McGilligan VE, Moore TC; Concordance between commondry eye diagnostic tests; British Journal of Ophthalmology, 2008Graham JE, Berrar D, McGilligan VE, Leccisotti A, Moore JE, Bron AJ, Moore CBT; Attitudes towards diagnostic testsand therapies for dry eye disease; Ophthalmic Research, 2008 (in press)123

Dr Victoria McGilliganResearch AssociateContact details:T: +44 (0)28 70323284v.mcgilligan@ulster.ac.ukDr McGilligan’s current research interests lie within the area of ocular immunology and disease diagnostics, havingpreviously worked for a diagnostic development company. She is currently employed as a Post Doctoral ResearchAssociate and visiting lecturer to UU, employed under an Invest NI Proof of Concept grant. This project focuseson determining biomarkers and diagnostic tests for ocular surface diseases. Dr McGilligan previously worked as aResearch Associate on a HPSS Infectious Diseases RRG Grant, “A study to compare the efficacy of two potentialdiagnostic assays: A Flourescein conjugated monoclonal antibody in vivo assay and nested real time PCR assay torapidly and accurately diagnose herpes simplex keratitis.” Dr McGilligan is also involved in a mulit-centered phase 3clinical trial along with visiting Professor Johnny Moore to test a new eye drop for dry eye syndrome. “A 3-monthstudy of the efficacy and safety of SVS20 in patients with bilateral moderate dry eye syndrome: A prospective, doublemasked,randomised, controlled, parallel-group, 3‐arm, phase III trial” sponsored by TRB Chemedica.Publications:McGilligan VE, Wallace JM, Heavey PM, Ridley DL, Rowland IR; The effect of nicotine in vitro on the integrity of tightjunctions in Caco-2 cell monolayers; Food Chem Toxicology, 45: 1593-1598, 2007McGilligan VE, Wallace JM, Heavey PM, Ridley DL, Rowland IR; Hypothesis about mechanisms through which nicotinemight exert its effect on the interdependence of inflammation and gut barrier function in ulcerative colitis; InflammatoryBowel Disease, 13: 108-115, 2007Hughes R, Kurth MJ, McGilligan V, McGlynn H, Rowland I; Effect of colonic bacterial metabolites on Caco-2 cellparacellular permeability in vitro; Nutrition & Cancer, 60: 259-266, 2008124

Dr Elena NovitskayaResearch AssociateDr Elena Novitskaya, Postdoctoral Research Associate and Ophthalmologist, works with Dr Tara Moore and MrJohnny Moore, Visiting Professor, on a multi centred research project aimed to improve diagnosis of Herpes SimplexKeratitis. In collaboration with clinicians in Bedford Moorfields Eye Hospital clinical material is obtained for viraldetection by multiplex PCR and optimisation experiments to visualize direct fluorescence of anti HSV antibodies onHSV infected corneal rims with modern ophthalmic equipment. Other interests include development and introductionof a novel method of corneal photography using fluorescein angiography settings of the fundus camera.Publications:Athanasiadis Y, Novitskaya ES, Nithyanandrajan G, Sharma A; Subconjunctival triamcinalone for the treatment ofcorneal graft rejection and new vessels; Cont. Lens Anterior Eye (Accepted 2008)Dean SJ, Novitskaya ES, Moore CBT, Moore JE, Sharma A; Documentation of corneal epithelial defects with fluoresceinenhanced digital fundus camera photography; Clinical and Experimental Ophthalmology, 36: 113-118, 2008Novitskaya ES, Dean SJ, Moore JE, Sharma A; A novel method to study fluorescein staining of the ocular surface usingthe fluorescein angiogram setting of the fundus camera; Cont Lens Anterior Eye, 30: 258-259, 2007Novitskaya ES, Moore JE, Athanasiadis Y, Moore CBT, Sharma A; A highly sensitive technique for imaging and effectivemonitoring of staining of the ocular surface defect; Eye, 23: 234-235, 2008Novitskaya ES, Moore JE, Dean SJ, Athanasiadis Y, McGilligan VE, Moore T, Sharma A; Imaging the epithelial defects ofthe ocular surface with digital fundus camera using fluorescein angiography settings; Cornea, 2008 (in press)Novitskaya ES, McGilligan VE, Moore J, Sharma A, Dean S, Moore T; Difficulties imaging Herpes Simplex Keratitis withFITC labelled anti- HSV-1 antibodies in an ex-vivo model; Cornea, 2008125

13. Externally Funded Projects during the reporting periodFunding Body C.E.C. - Framework 7 - SMEAmount Awarded £270,735TitleHYFFI: Hydrocolloids as functional food ingredients for gut healthGrant Holders Gill, Dr CIR; Mitchell, Mr PCFunding Body Food Standards AgencyAmount Awarded £161,958TitleVitamin D status and associated health outcomes: towards and evidence basis for definingvitamin D status sufficient to reduce risk of chronic diseaseGrant Holders Wallace, Dr J; Bonham, Dr MP; Campbell, Dr DJ; Cashman, Prof K (University College Cork -UCC); Duffy, Dr E; Kiely, Dr M (UCC); Magee, Dr P; Strain, Prof JJFunding Body Environmental Protection AgencyAmount Awarded £63,263TitleAntimicrobial Resistant enterococci (ARE) in Irish waters: Sources, transfers and impactsGrant Holders Dooley, Prof JSG; Arnscheidt, Dr J (Environmental Sciences – ES); Jordan, Dr P (ES);Naughton, Dr PJBFunding Body Marigot LtdAmount Awarded £265,027TitleThe effect of the mineral supplement Aquamin together with the short chainfructooligosaccaride Nutraflora on bone mineral densityGrant Holders Duffy, Dr E; Bonham, Dr MP; Magee, Dr P; Strain, Prof JJ; Wallace, Dr JFunding Body The British Dietetic AssociationAmount Awarded £7,360TitleOffice Bearer RenumerationGrant Holders McKelvey-Martin, Prof VJ; Douglas, Mrs PFunding Body C.E.C. - Framework 7Amount sought £113,793TitleBison: Bisociation networks for creative information discoveryGrant Holders Dubitzky, Prof W; Berrar, Dr D; Swain, Dr MT; Thompson, DR PFunding Body Alzheimer’s Disease SocietyAmount Awarded £163,334TitleNew strategies to prevent neurodegeneration in Alzheimer disease using insulin-likedrugsGrant Holders Holscher, Dr C; Gault, Dr VFunding Body The College of OptometristsAmount Awarded £1,550TitleSummer Scholarship - Psychophysical assessment of non-refractive optical defects inhealthy adultsGrant Holder Lauritzen, Mr JFunding Body Health Research BoardAmount Awarded £41,379TitleHealth Research CentreGrant Holders Stewart-Knox, Dr BJ; Bunting, Prof BP (Psychology);126

Funding Body University of Nottingham via UnileverAmount Awarded £150,414TitleThe effect of a catechin-enriched green tea extract on visceral fatGrant Holders Livingstone, Prof MBE; Wallace, Dr JFunding Body Food Safety Promotion BoardAmount Awarded £3,500TitlePROJECT EXT: The effect of gamma-tocopherol (gamma-T) on gamma-T status,antioxidant capacity and nitrosative stress in apparently healthy smokersGrant Holders Wallace, Dr J; Robson, Dr PJ; Strain, Prof JJFunding Body OrganonAmount Awarded £250,945TitleOrganon Research ProjectsGrant Holder Flatt, Prof PRFunding Body Environmental Protection AgencyAmount Awarded £140,802TitleDistribution, structure and functioning of subterranean fauna within Irishgroundwater systemsGrant Holders Arnscheidt, Dr J (ES); Dooley, Prof JSG; Hack, Dr CJ; Jordan, Dr P (ES); Rippey, Prof BHRT (ES)Funding Body Health Research BoardAmount Awarded £47,088TitleA study to identify research priorities for the therapy professions in IrelandGrant Holders McKenna, Prof HP (Nursing); Hasson, Dr F (Nursing); Keeney, Mrs SR (Nursing);Kelly, Dr GP (Health Sciences); McDonough, Prof SM (Health Sciences); Ward, Dr MFunding Body Organix FoundationAmount Awarded £120,000TitleEndocrine disruption and cancerGrant Holders Howard, Prof CV; Downes, Prof CS; Soto, Prof AFunding Body SAAD Trading & Contracting CompanyAmount Awarded £250,000TitlePharmacy Donation – SAADGrant Holders Curran, Prof CI (Nursing); McKelvey-Martin, Prof VJ; Simpson, Mrs J (Faculty of Life andHealth Sciences)Funding Body JISCAmount Awarded £2,100TitleJISC TechDis Heat - Video sharing for reflective learning in chemistry practicalsGrant Holders McClean, Dr S; Hagan, Dr PFunding Body Self FinancingAmount Awarded £100,000TitleSupport of Research in the SAAD CentreGrant Holder Bjourson, Prof AJFunding Body N.I.H.R. via Moorfields Eye HospitalAmount Awarded £6,300TitleBMRC Support for PhD Studentship on Spatial summation for chromatic and achromaticstimuli with age and glaucoma127

Grant Holder Anderson, Prof RSFunding Body Rank Prize Fund - Vacation StudentshipAmount Awarded £1,600TitleConsumption of meat in men aged 18-35 years - a pilot studyGrant Holder Duffy, Dr EFunding Body The Wellcome TrustAmount Awarded £155,877TitleForward Thinking, Northern IrelandGrant Holders McKelvey-Martin, Prof VJ; Clarke, Mrs L (Education); Humes, Dr G (BELB); Hunter,Mr D; McKenna, Dr DJFunding Body Dept of Agriculture and Food - FIRMAmount Awarded £415,683TitleNational Nutritional Phenotype DatabaseGrant Holders Strain, Prof JJ; Gibney, Prof MJ (UCD); McNulty, Prof HM; Ward, Dr MFunding Body I.N.I. NetworkingAmount Awarded £1,868TitleBioCAD - a computer-aided design system for biomedical imageryGrant Holder Saetzler, Dr KFunding Body B.B.S.R.C.Amount Awarded £292,188TitleGuidance Cues and Pattern Prediction in the Developing Retinal Vasculature: A combinedexperimental and Theoretical modelling approachGrant Holder Mitchell, Dr CAFunding Body Society for EndocrinologyAmount Awarded £9,500TitleCharacterization of NPAS2 as a novel vitamin D receptor (VDR) interacting protein. Anovel role for vitamin D in regulation of the peripheral clock?Grant Holder Thompson, Dr PFunding Body The British Dietetic AssociationAmount Awarded £7,366TitleOffice Bearer RenumerationGrant Holders McKelvey-Martin, Prof VJ; Douglas, Mrs PFunding Body The National Centre for Social Reseach - NatCenAmount Awarded £8,242Title National Diet and Nutrition Survey - Sodium Study 2007/8Grant Holder Livingstone, Prof MBEFunding Body Northern Ireland Chest Heart and Stroke AssociationAmount Awarded £11,792TitleThe evaluation of a school-based physical activity programme aimed at reducingchildhood obesity and CVD risk profileGrant Holders Gallagher, Dr AM; Bonham, Dr MPFunding Body Alzheimer’s Research TrustAmount Awarded £16,700TitleEquipment applicationGrant Holders Holscher, Dr C; McKeown, Prof SR128

Funding Body Alzheimer’s Research TrustAmount Awarded £85,150TitleNeuroprotective effects of GLP-1 analogues in animal models of Alzheimer’s disease andtype 2 diabetesGrant Holders Holscher, Dr C; Gault, Dr VFunding Body B.B.S.R.C.Amount Awarded £125,824TitleLive attenuated nairovirus vaccines: targeted mutations in a recombinant virusGrant Holders Bridgen, Dr A; Baron, Dr M (IAH Pirbright)Funding Body Dept of Agriculture and Food - FIRMAmount Awarded £122,072TitleNational food consumption databases for food safety and nutritionGrant Holder Livingstone, Prof MBEFunding Body DEL - Cross-Border R&D ProgrammeAmount Awarded £1,242,392TitleIrish Universities Nutrition Alliance Project: Building additional and sustainable researchcapacity in nutrition and bone health at the University of UlsterGrant Holders McNulty, Prof HM; Cashman, Prof K (UCC); Gibney, Prof MJ (UCD); Scott, Prof JS (TCD);Strain, Prof JJ; Wallace, Dr J; Ward, Dr MFunding Body R&D Office HPSS RRG - Cohesion FundAmount Awarded £5,000TitleThe role of IFITM1 in cancer invasionGrant Holders Bjourson, Prof AJ; Mitchell, Dr CAFunding Body I.N.I. - Proof of ConceptAmount Awarded £77,000TitlePersonalized medicine in breast cancer: predicting metastasies-free survival inlymph-node negative breast cancer patientsGrant Holders Bjourson, Prof AJ; Berrar, Dr DFunding Body Richard Bright VEGF Research TrustAmount Awarded £5,000TitleGeneration of mice over-expressing VEGF 164b from the A-crystallin promoterGrant Holders Mitchell, Dr CA; Devlin, Mrs AHFunding Body The Wellcome TrustAmount Awarded £79,964TitlePost-transcriptional control of DNA methylationreprogramming in the mouseGrant Holders Lees-Murdock, Dr D; Walsh, Dr CPFunding Body The Procter & Gamble CompanyAmount Awarded £6,000TitleLaboratory expenditureGrant Holders Strain, Prof JJ; Wallace, Dr J129

Funding Body Royal Irish AcademyAmount Awarded £1,699TitleThe kinetics of antiretroviral transport in cultured CD4 T cells and in primary humanlymphocytesGrant Holder Janneh, Dr OFunding Body The College of OptometristsAmount Awarded £1,500TitleA comparative study of relative pupil size, ocular accommodation and intraocularpressure between individuals taking antihistamines and that of a control groupGrant Holder McClelland, Ms JFunding Body R&D Office - HPSS - Cohesion FundAmount Awarded £1,995TitleSmall equipment grant for dual pen chart recorderGrant Holder O’Harte, Prof FPMFunding Body International Association for Dental Research/ GlaxoSmithKline Innov.Amount Awarded £1,781TitleCharacterization of a novel calcitonin gene related peptide cleavage enzymeGrant Holders Orr, Dr DF; Lundy, Dr F (QUB)Funding Body Dept of Agriculture and Food - MFFRIAmount Awarded £87,240TitleMarine Functional Foods Research ProgrammeGrant Holders Duffy, Dr E; Bonham, Dr MP; Campbell, Dr DJ; Gill, Dr CIR; Magee, Dr P; Strain, Prof JJ;Wallace, Dr JFunding Body SAAD Trading & Contracting CompanyAmount Awarded £250,000TitleDiabetes Research Equipment - SAAD DonationGrant Holders Flatt, Prof PR; Abdel-Wahab, Dr YHA; Curran, Prof CI (Nursing); O’Harte, Prof FPM;Simpson, Mrs J (Faculty of Life and Health Sciences)Funding Body R&D Office Cancer RRG Cohesion FundAmount Awarded £5,000TitleCharacterisation of aberrant Wnt signalling in Chronic Lymphoid LeukaemiaGrant Holders Wheadon, Dr H; Catherwood, Dr MA; Freeburn, Dr RWFunding Body Marigot LtdAmount Awarded £14,205TitleConsultancy earnings - fusion with MarigotGrant Holders Duffy, Dr E; Bonham, Dr MP; Magee, Dr P; Wallace, Dr JFunding Body The British Council - IAESTEAmount Awarded £3,200Title Placement Training for 2 IAESTE Trainees 2008Grant Holder Webba da Silva, Dr MM130

Funding Body R&D Office HPSS RRGAmount Awarded £45,156TitleA Study to Compare the Efficacy of two Potential Diagnostic Assays: A FlouresceinConjugated Monolonal Antibody Invivo Assay and Nested Real Time PCR AssayGrant Holders Moore, Dr CBT Moore, Dr J (Royal Group Hospitals - RGH); O’Neill,Dr H (RGH); Shah, Dr S (RGH); Sharma, Dr A (RGH)Funding Body The Wellcome TrustAmount Awarded £5,000TitleTransatlantic dialogue on emerging technologies: bioethics symposiumGrant Holders McKelvey-Martin, Prof VJ; Cameron, Prof N (Centre for Policy on Emerging Technology,USA)Funding Body Prostate Research Campaign UKAmount Awarded £30,000TitleCharacterization & evaluation of novel CYP2A4 inhibitors as anti-proliferative/prodifferentiating agents targeted towards hormone refractory prostate cancerGrant Holder Thompson, Dr PFunding Body Food Standards AgencyAmount Awarded £38,507TitleInvestigation of the Holo TC, the active component of circulating vitamin B12 as asensitive marker of dietary intakeGrant Holders McNulty, Prof HM; Hoey, Dr L; Pentieva, Dr KD; Strain, Prof JJ; Ward, Dr MFunding Body C.E.C. - Framework 7Amount Awarded £196,777TitleFACET: Flavours, additives and food contact material exposure taskGrant Holders McKevitt, Dr A; Livingstone, Prof MBE; Strain, Prof JJFunding Body Hunter Fleming LtdAmount Awarded £7,014TitleHF0220 StudyGrant Holders Holscher, Dr C; Dowey, Dr LFunding Body R&D Office - HPSS - Cohesion FundAmount Awarded £4,550TitleCharacterisation of the in vitro and in vivo antitumor effects of novel syntheticanalogues of dihydroartemisinin and cisplatinGrant Holders Janneh, Dr OFunding Body The Nuffield Foundation - BursaryAmount Awarded £1,400TitleThe anticancer effects of novel analogues of dihydroartemisininGrant Holder Janneh, Dr OTotal amount awarded £5,548,715131

14. BIOMEDICAL SCIENCES RESEARCH INSTITUTEPhD STUDENTS 2007-08Student: Talib Fadhil AbbasTitle: Effects of insulin signalling failure on learning abilities and on neuronal activity in animal models of type 2DiabetesSupervisors: Dr Christian Holscher, Dr Victor GaultStudent: Phillip AllsoppTitle: Effect of novel fructan carbohydrates on gut microflora and its activitiesSupervisors: Dr Chris Gill, Prof Ian Rowland (recognized)Student: Leslie AlticTitle: Novel functional foods based on folate enrichmentSupervisors: Dr Kristina Pentieva, Prof Helene McNultyStudent: Sarah AtkinsonTitle: Anti-angiogenic proteins and human Intra-Uterine Growth RestrictionSupervisors: Dr Christopher Mitchell, Dr Stephen McCleanStudent: Nadina AskinTitle: Intake and status of vitamin B12 in healthy younger and older adults: implications for food fortification policySupervisors: Prof Helene McNulty, Dr Kristina Pentieva, Dr Mary WardStudent: Gianfranco BartoliniTitle: Molecular mechanisms for anti-tumour activity protease activity from grain legumes.Supervisors: Dr Pamela Magee, Dr Chris Gill, Dr Richard Owuso-Apenten, Dr Omar JannehStudent: Tomasz BorkowskiTitle: Evaluation of plant extracts for anticancer potential in in vitro assay using colon cancer cellsSupervisors: Dr Satyajit Sarker, Dr Chris Gill, Prof Ian Rowland (recognised)Student: Gillian BrowneTitle: The importance of hypoxia in the metastatic spread of prostate tumoursSupervisors: Dr Jenny Worthington, Prof Stephanie McKeownStudent: Sui-Wai ChoiTitle: Antioxidants in health and disease with particular focus on Vitamin CSupervisors: Prof Sean Strain, Prof Bernie Hannigan, Prof I Benzie (recognised)Student: Emma Marie CoatesTitle: Anti-cancer effects of soft fruit phytochemicals.Supervisors: Dr Chris Gill, Dr Pamela Magee, Dr Gordon McDougall, Prof Ian Rowland (recognised)Student: Victoria DanielsTitle: Antibiotic resistant bacteria in Irish waters: molecular epidemiology and hydrological control.Supervisors: Dr James Dooley, Dr Joerg Arnscheidt, Dr Patrick Naughton, Dr Phillip JordanStudent: Peter DickinsonTitle: A stereological investigation of multiple cellular signals as a means to understand tumour infrastructureSupervisors: Prof Vyvyan Howard, Dr Angela McGlynn132

Student: Edwina DobbinTitle: Proteomic analysis of the signalling events involved in leukaemic transformation by the tyrosine kinase fusionprotein Tel/PDGF-R.Supervisors: Dr Helen Wheadon, Dr Robin FreeburnStudent: Sharon Marie DohertyTitle: Novel advanced imaging of nanostructures in foods.Supervisors: Prof Vyvyan Howard, Dr George McKerrStudent: Fiona DonnellyTitle: The identification and characterisation of the master regulator genes involved in invasion and metastasis inbreast cancerSupervisors: Prof Tony Bjourson, Dr Christopher MitchellStudent: Stephen DrainTitle: Molecular genetics and aetiology of multiple myelomaSupervisors: Prof Tony Bjourson, Dr Jenny Worthington, Prof Denis Alexander (Recognised)Student: Orla DugganTitle: An investigation of T-cell biology in nonagenariansSupervisors: Dr Robin Freeburn, Dr Helen Wheadon, Prof Yvonne Barnett (Recognised)Student: Philip DunneTitle: DNA methylation, mismatch repair and drug resistance.Supervisors: Dr Colum Walsh, Dr Diane Lees-Murdock, Dr Jennifer McDaid (Recognised Supervisor)Student: Wolfgang DusekTitle: Learning success and convergence insufficiency: a new treatment approach.Supervisors: Dr Julie McClelland, Prof Barbara Pierscionek, Dr Brigette Trinkl (Recognised)Student: Anupma Dwivedi,Title: Studies on bacterial targeted treatment of solid tumoursSupervisors: Dr Poonam Singh, Prof Tony McHaleStudent: David EganTitle: To investigate the incidence of salmonella in pigs and pork meat on the island of IrelandSupervisors: Dr Patrick Naughton, Dr James DooleyStudent: Samia Mohamed El OjaliTitle: Immunology mechanisms involved in intracellular microbial infectionsSupervisors: Dr Tara MooreStudent: Andreas ElsaesserTitle: Biophysical Interactions of Nanoparticles and CellsSupervisors: Prof Vyvyan Howard, Dr George McKerrStudent: Laura (Kirsty) ForsytheTitle: Adipose Tissue as a source of inflammatory factorsSupervisors: Prof Barbara Livingstone, Dr Julie WallaceStudent: Pamela Anne FrizelleTitle: Development and testing of stable bioactive peptide analogues of CCK-8 with enhanced satiety and insulinotropicactivities.Supervisors: Prof Finbar O'Harte, Prof Peter Flatt133

Student: Simon GenglerTitle: Effects of beta-amyloid on synaptic plasticity and learning processSupervisors: Dr Christian Holscher, Dr Victor GaultStudent: Mairead GoodallTitle: The effects of MeHg exposure and dietary status of pregnant women on infant neurodevelopmentSupervisors: Prof Sean Strain, Dr Kristina PentievaStudent: Lesley Hamill (nee Wright)Title: Does dietary iron supplementation inhibit the potential beneficial effects of phenolics in plant foods?Supervisors: Dr Rob Welch, Prof Sean Strain, Dr Ruth Price, Dr Julie WallaceStudent: Alison HamiltonTitle: Analysis of anatomical neuronal changes in the brain of a mouse model of Alzheimer's diseaseSupervisors: Dr Christian Holscher, Prof Vyvyan HowardStudent: Johan HazekampTitle: Ramen spectroscopy in cryo dual beam scanning electron microscopySupervisors: Prof Vyvyan Howard, Dr George McKerr, Prof M Reed (recognised)Student: Stephanie HodgeTitle: Psychological underpinnings of metabolic syndromeSupervisors: Dr Barbara Stewart Knox, Dr Ian Bradbury, Prof Sean StrainStudent: Paul HughesTitle: Electro-biosorbative Recovery of Economic Metals from Waste StreamsSupervisors: Prof Tony McHale, Dr Poonam SinghStudent: Catherine Frances HughesTitle: Intervention studies with vitamin B-12: implications for food fortification policy and dietary requirements forprevention of disease.Supervisors: Prof Helene McNulty, Dr Mary WardStudent: Shailesh JainTitle: Can a post Genomic Analysis of Clostridium Difficile validate use of comparative studies to elevate understandingof genome functionSupervisors: Dr Nigel Ternan, Prof Geoffrey McMullanStudent: Ramandeep KaurTitle: Whole-grains and health-a metabolomics approachSupervisors: Dr Rob Welch, Dr Julie Wallace, Prof Sean Strain, Dr Ruth PriceStudent: Edel KeaveneyTitle: Bioavailability and bioactivity of whole grain componentsSupervisors: Dr Rob Welch, Dr Julie Wallace, , Dr Ruth Price, Prof Sean StrainStudent: Jonathan KeenanTitle: Crystallin distribution patterns and interactions in the eye lens.Supervisors: Prof Barbara Pierscionek, Dr David OrrStudent: Mary KellyTitle: Investigation of the contribution made by food portion size to food and energy intakeSupervisors: Prof Barbara Livingstone, Dr Mary Hannon-Fletcher, Dr Julie Wallace134

Student: Barry KerrTitle: Metabolic factors regulating the expression and activity of 11b Hydroxysteroid Dehydrogenase type 1(11b-HSD1): a Novel Drug Target for the treatment of Type 2 Diabetes and ObesitySupervisors: Prof Peter Flatt, Dr Victor GaultStudent: Johan KleinTitle: Attribution of visual loss in patients presenting with glaucoma and cataract using psychophysical methodssuitable for clinical useSupervisors: Dr Jan Lauritzen, Prof Barbara PierscionekStudent: Wan Chi LamTitle: Characterisation of DNA architectures as drug targets in angiogenesis.Supervisors: Dr Mateus Webba da Silva, Dr Christopher Mitchell, Dr Jenny WorthingtonStudent: Ho-Tak LauTitle: Exploring the role of key proteins in regulating reprogramming in stem cells.Supervisors: Dr Diane Lees-Murdock, Dr Colum WalshStudent: Wai-Ping LeeTitle: A study of the role of reversible sumoylation of the Vitamin A and Vitamin B signalling pathwaysSupervisors: Dr Paul Thompson, Dr Colum WalshStudent: Ying Suet LiTitle: Virus-mediated gene therapy using an erythrocyte-based carrier systemSupervisors: Prof Tony McHale, Prof Tony BjoursonStudent: Jayne LougheryTitle: Investigating a protein expressed in male stem cells and involved in cancerSupervisors: Dr Colum Walsh, Dr Helen WheadonStudent: Nason James Maani-HessariTitle: DNA topologies in the regulatory genome.Supervisors: Dr Mateus Webba da Silva, Dr Karsten MelcherStudent: Maria Joao MachadoTitle: Angiogenesis in healing wounds: bioimaging in situSupervisors: Dr Christopher Mitchell, Dr George McKerrStudent: Crispin MadavoTitle: Molecular characterisastion of selected neuropeptides from ovine intestinal tissue and from the ovine parasitemoniezia expansaSupervisors: Prof Tony Bjourson, Dr Stephen McCleanStudent: Yasunori MaedaTitle: Molecular dection and identification of cryptosporidium parvumSupervisors: Dr Colm Lowery, Dr William Snelling (recognised), Dr James Dooley, Mr John Moore (Recognised)Student: Catherine MaingotTitle: The use of photo-sensitive erythrocytes in gene therapySupervisors: Prof Tony McHale, Prof Tony BjoursonStudent: Sarah Jean MatzenTitle: Comparative functional Genomics: A means to elucidate the genetic determinants of thermophily in theeubacterial genus Geobacillus.Supervisors: Prof Geoffrey McMullan, Dr Nigel Ternan135

Student: Anisha MazumdarTitle: Analysis of biomolecules from higher plants to treat diseasesSupervisors: Dr Poonam Singh, Prof Tony McHale, Dr Satyajit SarkerStudent: Alison McAfeeTitle: Contribution of beef and lamb from grass-fed animals to intake of long chain omega-3 polyunsaturated fattyacidsSupervisors: Prof Sean Strain, Dr Julie Wallace, Dr Emeir Duffy, Dr Maxine BonhamStudent: Colm McAlindenTitle: LASER: outcomes of refractive surgery.Supervisors: Prof Barbara Pierscionek, Dr Jonny Moore (Recog), Prof Bryan ScotneyStudent: Roisin Mary McAllisterTitle: Mitotic spindle assembly checkpointSupervisors: Prof Tony Bjourson, Prof Stephen DownesStudent: Darragh McArtTitle: Automated analysis of the comet FISH assay.Supervisors: Dr Kurt Saetzler, Dr George McKerr, Dr Gillian WassonStudent: Seona McErleanTitle: Genetic profiling of breast cancerSupervisors: Prof Tony Bjourson, Dr Paul ThompsonStudent: Paula McGurkTitle: Associations between maternal diet, lifestyle factors, pregnancy outcomes and glycaemic control in pregnantwomanSupervisors: Prof Peter Flatt, Dr Alyson HillStudent: Grainne Maire McNeeceTitle: Identification of antibiotic resistant genes in poultrySupervisors: Dr Patrick Naughton, Dr James DooleyStudent: Louise MingTitle: The role of hypoxia in malignant progression and its effect on metastatic potential in androgen-dependantprostate cancer.Supervisors: Prof Stephanie McKeown, Dr Jenny WorthingtonStudent: Duarte MolhaTitle: A data mining approach to thermophily in eubacteriaSupervisors: Dr Catherine Hack, Prof Roger MarchantStudent: Sara MooreTitle: The isolation and characterisation of natural products of pharmaceutical significance from complex biologicalmatricesSupervisors: Dr Stephen McClean, Dr Victor Gault, Prof Franklin SmythStudent: Therese MorganTitle: Effects of accumulated walking in cardiovascular risk in obesitySupervisors: Dr Alison Gallagher, Dr Marie Murphy, Dr Gareth DavisonStudent: Amy MulleeTitle: Studies on the vitamin E isomer, γ-tocopherol (γ-T): the effect of dietary intake and body composition on statusand functional markers in healthy volunteersSupervisors: Dr Julie Wallace, Prof Sean Strain136

Student: Ming Tak NgTitle: Clinical investigation of the involvement of glycated forms of glucagons-like peptide-1 and gastric inhibitorypolypeptide in glucose metabolism and diabetesSupervisors: Dr Aine McKillop, Dr Yasser Abdel-WahabStudent: Nikolitsa NomikouTitle: Electric field-mediated biosorption - Assessing potential applicationsSupervisors: Prof Roger Marchant, Prof Tony McHale, Dr Poonam SinghStudent: Alan O'DohertyTitle: Investigating a protein expressed in male stem cellsSupervisors: Dr Colum Walsh, Dr Helen WheadonStudent: Edwina O'DohertyTitle: Novel imaging of micro and nano-structure for hygiene and personal care applications.Supervisors: Dr George McKerr, Prof Vyvyan HowardStudent: Elizabeth O'DonoghueTitle: Epidemiology of Myopia in a UK child populationSupervisors: Dr Kathryn Saunders, Dr Julie McClellandStudent: Vitaliy OstropytskyyTitle: Management, warehousing and mining of protein folding and unfolding data.Supervisors: Prof Werner Dubitzky, Dr Daniel Berrar, Dr Martin SwainStudent: Heather ParrTitle: Psycho-social and lifestyle factors associated with metabolic syndromeSupervisors: Dr Barbara Stewart Knox, Prof Brendan BuntingStudent: Jennifer PearsonTitle: Molecular investigation of faecal waterSupervisors: Dr Chris Gill, Dr Pamela Magee, Prof Ian Rowland (recognised)Student: Amedea PerfumoTitle: Investigation of bacterial biosurfactant production for industrial useSupervisors: Prof Ibrahim Banat, Prof Roger MarchantStudent: Catherine PollockTitle: Receptor interacting protein (RIP 140) as a regulator of the vitamin D signal pathwaySupervisors: Dr Paul Thompson, Dr Robin FreeburnStudent: Gavin PowerTitle: Isolation, structural characterisation and mechanisms of action of novel insulin-releasing peptides from amphibianskin secretions characterisation and mechanisms of action of novel insulin-releasingpeptides from amphibian skin secretions.Supervisors: Dr Yasser Abdel-Wahab, Prof Peter FlattStudent: Shazia RashidTitle: Cytotoxic and mutagenic effects of active extracts from funalia trogll mushroom on mammalian cancer cells.Supervisors: Prof Ibrahim Banat, Prof Roger Marchant, Dr Jenny WorthingtonStudent: Tony RedmondTitle: Spatial summation for chromatic and achromatic stimuli with age and glaucomaSupervisors: Prof Roger Anderson, Dr Margarita Vidinova137

Student: Clare RyanTitle: How does the nervous system in taenia crassiceps reconstruct within the offspringSupervisors: Dr George McKerr, Dr Barry O'HaganStudent: Oliver SchmidtTitle: Bisociation Networks for Creative Information Discovery in BiologySupervisors: Dr Paul Thompson, Prof Werner Dubitzky, Dr Daniel Berrar, Dr Martin SwainStudent: Natalie ScottTitle: Investigating the Key Regulators of Invasion and Metastasis in a Breast Cancer Cell Line ModelSupervisors: Prof Tony Bjourson, Dr Jenny WorthingtonStudent: Roberta Scott (MPhil)Title: Biological and bioinformatic analysis of GeobacillusSupervisors: Dr Kay Hack, Prof Roger MarchantStudent: Siobhan ScullionTitle: Investigation of the detrimental pancreatic beta-cell actions of key metabolic syndrome risk factor,homocysteineSupervisors: Dr Neville McClenaghan, Dr Stephen PattersonStudent: Mary SlevinTitle: The effect of the mineral supplement, Aquamin on bone density in postmenopausal womenSupervisors: Dr Emeir Duffy, Dr Maxine Bonham, Dr Julie Wallace, Dr Pamela MageeStudent: Stephen SmythTitle: Geneotyping of cryptospridium in Northern Ireland using laser capture microdissection and PCRSupervisors: Dr Colm Lowery, Dr James Dooley, Dr William Snelling (recognised)Student: Malay SrivastavaTitle: A data mining approach to understanding thermophilySupervisors: Dr Catherine Hack, Dr Poonam Singh, Prof Roger MarchantStudent: Ya Hui TangTitle: The role of CYBR in tumour leukocyte trafficking in vivoSupervisors: Dr Christopher Mitchell, Dr Kurt SaetzlerStudent: Ashley TaylorTitle: Novel therapeutic approaches to alleviation of insulin resistance and diabetes.Supervisors: Dr Victor Gault, Dr Aine McKillopStudent: Keith Gareth ThomasTitle: The role of the NOTCH1 receptor in the pathogenesis of T cell acute lymphoblastic leukaemia.Supervisors: Dr Robin Freeburn, Dr Helen WheadonStudent: Elizabeth WalkerTitle: Investigation of Changes in the Testis under Varying Developmental Conditions: A stereological StudySupervisors: Prof Vyvyan Howard, Dr George McKerrStudent: Chong WangTitle: Computational Biology Study into Genetic Causes of Long QT SyndromeSupervisors: Prof Werner Dubitzky, Dr Christopher NugentStudent: Johannes WeisenseeTitle: Evaluation of a novel method to measure optic head perfusion in open angle glaucomaSupervisors: Prof Roger Anderson, Dr Raymond Beirne, Prof Barbara Pierscionek138

Student: Claire WhittleTitle: Homocysteine related B vitamins and genetic factors, and bone healthSupervisors: Prof Helene McNulty, Prof Sean Strain, Dr Mary WardStudent: Carol WilsonTitle: Ribflavin, Blood pressure and the methylenetetrahydrofolate reductase (MTHDR) 677c -> T polymorphism.Supervisors: Dr Mary Ward, Prof Helene McNultyStudent: Clive WolsleyTitle: The relationship between measurements of retinal thickness using optical coherence tomography and retinalfunction using multifocal electrophysiology in patients with myopia and retinal disordersSupervisors: Prof Roger Anderson, Dr Kathryn SaundersStudent: Ravi YaragandlaTitle: Induction of immune responses against respiratory virusesSupervisors: Dr Daniel Quinn Dr Tara MooreStudent: Peipei ZhongTitle: Identification of activator-coactivator contacts in yeastSupervisors: Dr Karsten Melcher, Dr Paul Thompson139

CONGRATULATIONS TO THE FOLLOWING POSTGRADUATE STUDENTS WHOGRADUATED DURING 2007-08Clifford Barnes Winter 2007Maria Barnes Winter 2007Katherine Feeney Winter 2007Hendrik Fuss Winter 2007Paul Irvine Winter 2007Katherine McAllister Winter 2007Cathy McGeough Winter 2007Briege McNulty Winter 2007Fionnuala O'Donnell Winter 2007Michelle Share Winter 2007Louise Beggs Summer 2008Conal Bunting (Mphil) Summer 2008Joseph Christie Summer 2008Eleanor Conant Summer 2008Pamela Corrigan Summer 2008Declan Doherty Summer 2008Hong Guo Summer 2008Caitriona Kelly Summer 2008Orla Maguire Summer 2008Tracey McCaffrey Summer 2008Helen McCarthy Summer 2008Paula McClean (nee Given) Summer 2008Julie Sittlington Summer 2008Top Up Your Vitamins For Winter HealthDr Maria Barnes from north Belfast received her PhD in Biomedical Sciences atthe Coleraine campus on 18th December 2007.Having graduated from the University in 2003 with a BSc Honours in BiomedicalSciences, Maria carried on her studies with a PhD researching Vitamin D statusamong people in Northern Ireland and its implications for health.This research has shown that around half the population in Northern Ireland have insufficient levels of Vitamin D intheir blood – something which Dr Barnes said “is particularly apparent during the winter months” “Vitamin D is primarilymade in the skin through the action of sunlight and with shorter days in the winter, vitamin D levels will decrease and thereforepeople should consider taking supplementation to keep these levels up.”“An insufficiency of Vitamin D has potential implications for diseases such as osteoporosis, some cancers - breast, prostate andcolon - multiple sclerosis and diabetes mellitus among others.”140

In 2003, Maria was among the first graduates to receive the Diploma in Professional Practice in Pathology havingsuccessfully achieved the Health Professions Council registration in Haematology and Hospital Blood Transfusion-– which is required for work in hospital laboratories.Having wielded some significant results throughout her doctorate, Dr Barnes has had her research published ininfluential medical journals, most notably ‘European Journal of Clinical Nutrition’ and ‘Multiple Sclerosis’.Not content with spending seven years studying at the Coleraine campus, Dr Barnes currently works as a ResearchAssociate at the University’s Centre for Molecular Biosciences.141