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ANNUAL REPORT 2003
CONWAY INSTITUTE OF BIOMOLECULAR AND BIOMEDICAL RESEARCH The mission of the Conway Institute is to promote knowledge, health and economic advancement though excellence in biomolecular and biomedical research. CONTENTS > ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH LETTER FROM PRESIDENT, University College Dublin 2
LETTER FROM CHAIR, Board of Management, Conway Institute of Biomolecular & Biomedical Research 3
FOREWORD BY DIRECTOR, Conway Institute of Biomolecular & Biomedical Research 5
CONWAY INSTITUTE OVERVIEW 6 Research Programme 6 Funding 6 Research Centres 7 Management 7
RESEARCH OUTCOMES 9 Key Performance Indicators 9 Publications 9 Grant Income 9 Postgraduate Thesis Submissions 9
HIGHLIGHTS 10 New Appointments 11 Programme Grant Awards 14 High Impact Publications
CENTRE REPORTS 15 Centre for Synthesis & Chemical Biology 15 Dublin Molecular Medicine Centre 15
CONWAY INSTITUTE TODAY 18 An Innovative Research Building 18 Technology 18 Education Programme 18 Discipline Integration & Technology Transfer Seminar Series 18 Information 19 Communication 19 Technology Transfer & Commercialisation 19
CONTACT US 21 Address/telephone/email/web 21 Directorate Team Details 21 Location 21
APPENDIX Grants Awarded 22 Publications by Investigator 29 Thesis Submissions 45 Lectures in Discipline Integration & Technology Transfer Series 2002/2003 46 ONE LETTER FROM DR. ART COSGROVE, >President, University College Dublin ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH
Dr. Art Cosgrove
It is with great pleasure that I introduce the first formal Annual Report of the Conway Institute of Biomolecular and Biomedical Research. The Conway Institute is the flagship research enterprise at University College Dublin. The Institute gathers together a critical mass of life sciences researchers, with complementary expertise and skills; their shared objective is to understand in greater detail the root causes of a number of important diseases and through this to develop more effective treatments.
The funding made available by the Higher Education Authority under the Programme for Research in Third-Level Institutions has provided these researchers with world-class laboratories and state-of-the-art equipment. These facilities equal those available anywhere else in the world, which allows the Conway Institute to continue to attract the very best scientists and students, who will contribute greatly to the research and educational milieu at UCD.
The very existence of the Conway Institute is a tribute to those in public life who share a vision that, through consistent strategic investment in research, we can foster a knowledge economy that will safeguard our social and economic development. The researchers at the Conway Institute will make a fundamental contribution to turning this vision into a reality.
This is an exciting time for the Conway Institute as the research activity, which has previously been carried out at various campus and off-campus locations, is consolidated in a wonderful new building. This annual report outlines the very impressive achievements to date. We can look forward to even more significant advances in coming years.
The Institute was named after Professor E. J. Conway, F.R.S., one of the most distinguished scientists in the history of UCD. I am confident that the activities and achievements of the Conway Institute are a fitting tribute to his memory.
Dr. Art Cosgrove President University College Dublin TWO LETTER FROM MR. DENIS BROSNAN, >Chairman, Conway Board of Management ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH
Mr. Denis Brosnan
I am delighted to present the first Annual Report of the Conway Institute. The Board of Management of the Conway Institute formally met for the first time on July 2, 2002 taking over from an interim Board, which had carefully and successfully overseen the early development of the Institute.
This annual report brings to a close the first chapter in the development of the Conway Institute. Dr. Andy Robertson served as Director from August 2000 to May 2003 and, in this time supervised the completion and equipping of the new research building, reorganised the scientific activities of the Institute and developed strong partnerships with other third level institutions. The Board wishes Dr. Robertson every success in his new post as Professor and Head of the School of Biomedical & Molecular Sciences at the University of Surrey.
The Institute, now firmly established, is moving into a new phase of development. It is critically important that, to ensure growth and competitiveness, an ongoing, stable investment in research infrastructure and activity is maintained. The Board and the Institute must justify this investment by clearly articulating the successes, benefits and outcomes to date and defining a strategic plan for the future.
The most important objective in the coming year will be to develop and publish a clear strategic plan, which will ensure the development of the Institute and plot the route to success. The objectives are clear. The Conway Institute will be internationally recognised as an important centre for research in several key areas; it will have a reputation for excellence in teaching and training; it will form close and productive relationships with industry and will be acknowledged by the public as an important contributor to our social and economic development. Great progress has been made, yet much more can be achieved.
Mr. Denis Brosnan Chairman Board of Management Conway Institute of Biomolecular and Biomedical Research THREE CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH ANNUAL REPORT 2003 FOUR FOREWORD BY DR. PHILIP NOLAN, Acting Director, Conway Institute of Biomolecular >and Biomedical Research ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH
Dr. Philip Nolan, Acting Director, Conway Institute of Biomolecular and Biomedical Research
This Annual Report outlines the achievements of researchers at the Conway Institute for the period from July 1st 2002 – June 30th 2003. We have so far exceeded the targets set for the Institute in the original proposals under the Programme for Research in Third- Level Institutions. Given that the physical infrastructure, laboratories and equipment to support the Conway Institute are only nearing completion, it is clear that the spirit of cooperation and collegiality created through the Institute has already galvanised research activity. Now that many of the researchers involved in the Institute are gathered together under one roof, with world- class facilities and equipment at their disposal, I am confident that the next few years will see new, significant and exciting developments arising from our research programme.
We pursue our research in a wider context – public funding for research is predicated on there being significant benefits to society, in areas such as health, education, economic development and social gain. The Conway Institute is committed to realising these benefits. Excellence in research is fundamental. Equally, strong partnerships with industry, close links with academic medicine as a vital component of a quality health service and an ongoing commitment to teaching and learning at all levels are essential if that excellence is to be of value to the community that supports our work. These considerations must form the basis for our strategic planning.
Dr. Philip Nolan, Acting Director, Conway Institute of Biomolecular and Biomedical Research FIVE CONWAY INSTITUTE OVERVIEW >Development of the Conway Institute ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH The Conway Institute of Biomolecular and Biomedical Research is physicians working in the Conway Institute and affiliated hospitals a major new research enterprise at University College Dublin, are making important contributions to our understanding of the named after Professor E.J. Conway, the first Chair in Biochemistry causes and consequences of diabetes, arthritis, Alzheimer’s and Pharmacology at UCD. The research programme at the Conway disease, cardiovascular and lung disorders as well as breast and Institute focuses on biological molecules; examining how individual prostate cancer. molecules contribute to the normal operation of cells and organs and how this can be disrupted by disease. The knowledge gained Crucial to the success of the Conway Institute is the development improves our understanding of the causes and effects of disease, of strong external partnerships. These include: which leads to simpler, more reliable diagnostic tests and innovative, more effective treatments for human and animal disorders. • Dublin Molecular Medicine Centre (DMMC), a partnership with Trinity College Dublin (TCD) and the Royal College of Surgeons Founded in 1999, the Conway Institute received funding from the in Ireland (RCSI). Higher Education Authority and private donors through the Programme for Research in Third Level Institutions. The total • Centre for Synthesis and Chemical Biology, which brings funding committed to date amounts to 284 million. together expertise in chemical biology from UCD, TCD and RCSI.
RESEARCH PROGRAMME FUNDING
The Institute has drawn together a research team from such diverse The Conway Institute of Biomolecular and Biomedical Research scientific backgrounds as chemistry, biochemistry, pharmacology, received funding from the Higher Education Authority and a private physiology, medicine, surgery, engineering, agriculture and donor under Cycles 1, 2 and 3 of the Programme for Research in veterinary medicine. By facilitating the interaction of scientists Third-Level Institutions. The total amount of funding committed from different disciplines, with different skills and viewpoints, the to the Conway Institute and related programmes over these three 2 Conway Institute allows them to collaboratively apply their research cycles was 84 million. The breakdown of this funding can be efforts to the resolution of important scientific problems. summarised as follows:
The research programme is organised around three centres: Cycle I It was proposed that the Conway Institute of Biomolecular and • The Centre for Synthesis and Chemical Biology concentrates Biomedical Research would represent a new approach to scientific on creating and understanding new molecules, which will lead research within University College Dublin by creating a critical to the discovery of new or refined drugs and the development mass of researchers collaborating across traditional faculty and of innovative tools to investigate biological problems. departmental boundaries and across disciplines. The ultimate goal of this new institute would be to identify new targets for the • The Centre for Integrative Biology examines the role of treatment of both animal and human disease. individual molecules in the overall function of cells, tissues and organs. In the first cycle of funding, 226.71 million was provided to build, equip and operate a state-of-the-art research facility that would • The Centre for Molecular Medicine investigates the molecular provide laboratory and writing space for the purpose of biomolecular basis of disease by unravelling the causes of disorders and and biomedical research. Funding was also provided to appoint explaining their effects on the body. Conway Research Fellows, selected on a competitive basis to foster collaborative research projects involving investigators from at least Through extensive interaction, the activities of these centres create two different disciplines. a research continuum, which ensures that breakthroughs in chemical and biological science are rapidly applied to the Cycle II investigation and treatment of disease. The Conway Institute A unique research partnership was created between University operates from “molecules to medicine” and from “bench to bedside”. College Dublin and Trinity College Dublin in the shape of the Dublin Molecular Medicine Centre (DMMC). The research The research activity of the Conway Institute can also be described programme of the DMMC is now being delivered by the Conway in terms of the biological problem or type of disease being studied. Institute in UCD and the Institute of Molecular Medicine on the There are four major areas of focus: St James’s Hospital site of TCD. An additional 212.53 million was provided to expand the Conway building to incorporate its • Cancer component of the DMMC and to provide ongoing administrative • Vascular biology and operational support for the research programme, in particular • Neuroscience its inter-institutional elements. • Infection, immunity and inflammation. Cycle III Strong links with a number of major academic teaching hospitals The Centre for Synthesis and Chemical Biology (CSCB) was SIX have been developed to underpin this activity. Scientists and proposed as a further strategic development bringing together
CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH ANNUAL REPORT 2003 EIGHT
HIGHLIGHTS > ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH NEW APPOINTMENTS into and progression through the G1 phase of the mammalian cell cycle. He graduated with a joint honours B.Sc. in Chemistry & Professorships Biochemistry in 1982 and received his Ph.D. from the University In order to compete at the forefront of international biosciences of Cambridge in 1986. He spent two years as Elmore Medical research over the coming years, the Conway Institute has appointed Research Fellow at Cambridge before moving to the University of four senior academics to provide dynamic leadership for the Liverpool, where he was funded at first by the Wellcome Trust. He Conway Institute and its partners during the early developmental was appointed Senior Lecturer in 2001. He has published 26 papers years. The four Chairs will play leading roles in the delivery of the and is a section editor for ‘Encyclopaedia of Genetics, Genomics, Conway Research Programme, in addition to the implementation Proteomics and Bioinformatics’. of Dublin-wide technology platforms and research programmes, under the auspices of the Programme for Human Genomics and Principal Investigators through cross-institutional collaborations. During the report period, the following researchers have been appointed as Principal Investigators in the Institute. We Dr. Steve Pennington took up position as the Chair of Proteomics acknowledge their achievements in research and wish them in June 2003. The new Chair of Bioinformatics, Dr. Des Higgins will continued success. take up his position in September 2003. Professors Helen Colhoun and Paul McKeigue have been appointed as Professors of Genetic Dr. R. William Watson joined the Department of Surgery in 1997. Epidemiology. Their contracts will begin in January 2004. His research interests include cellular and molecular mechanisms regulating apoptosis in inflammatory neutrophils and prostate Prof. Helen Colhoun has been appointed Professor of Genetic cancer cells in vivo and in vitro; the profiling of pro- and anti- Epidemiology. She qualified in Medicine from the National apoptotic genes in patients with inflammatory disorders, University of Ireland, Galway in 1988 and subsequently obtained specifically sepsis and characterising the apoptotic phenotype an M.Sc in Public Health from the London School of Hygiene and during the differentiation process of neutrophils and basal prostate Tropical Medicine and the degree of M.D. from the National epithelial cells. University of Ireland. She comes to the Conway Institute from a post as Professor in the Department of Epidemiology and Public Dr. Cormac Taylor has been a researcher and lecturer at UCD Health, University College London. Her major areas of research since 2001. His research interests include the impact of hypoxia interest are the epidemiology of diabetes and cardiovascular on cellular function, transcriptional regulation and post- disease. She has published over 40 papers in international peer- translational modification. review journals. Her appointment is jointly funded by the Conway Institute and the Dublin Molecular Medicine Centre. Dr. Caroline Herron joined the Department of Human Anatomy & Physiology as a lecturer in 1998. Her research interests include Prof. Des Higgins joins the Conway Institute as Professor of hippocampal synaptic transmission and mechanisms underlying Bioinformatics. He received his Ph.D. from Trinity College Dublin in plasticity, molecular mechanisms underlying the effects of Beta- 1988 and has held posts in the European Molecular Biology amyloid protein and the interaction of neuronal nicotinic receptors Laboratory in Heidelberg, the European Bioinformatics Institute, with amyloid beta peptide. Hinxton, UK and most recently in the Department of Biochemistry, University College Cork. He has published almost 50 peer-reviewed Dr. William Gallagher became an UCD lecturer in 2001. His research papers and 11 book chapters. He developed the CLUSTAL software, interests include cancer biology, molecular therapeutics and computer programs to identify sequences of DNA within genes, functional genomics. which is now used in laboratories throughout the world. His appointment is funded through the Dublin Molecular Medicine Centre. Dr. David Brayden joined the Faculty of Veterinary Medicine as a lecturer in 2001. His research interests include drug, polymer, Prof. Paul McKeigue will join the Conway Institute from January bacteria and prion attachment and delivery across intestinal 2004 as Professor of Genetic Epidemiology. He graduated in epithelial cells and Peyer’s patch M cells of the gut; epithelial tight Medicine from Cambridge University in 1979 and obtained a Ph.D. junction regulation in inflammatory bowel disease and P- in Community Medicine from the University of London in 1990. He glycoprotein drug efflux systems in the gut and blood-brain barrier. is currently Professor of Metabolic and Genetic Epidemiology in the London School of Hygiene and Tropical Medicine. He has Dr. Marguerite Clynes became a special lecturer in Paediatrics in published over 80 papers. His interest in ethnic variations in UCD in 2000. Her research interests include adherence of cardiovascular disease and diabetes led to his current research Helicobacter pylori to the gastric mucosa, virulence of programme in genetic epidemiology. He has a particular interest Campylobacter jejuni and Cryptosporidium parvum pathogenesis. in mathematical statistics. His post is funded through the Dublin Molecular Medicine Centre. Dr. Edward Timoshenko has been a lecturer in the Department of Chemistry, UCD since 1997. His research interests include Prof. Stephen Pennington comes to the Conway Institute as finding mechanisms for controlled self-assembly of water-
TEN Professor of Proteomics. His research is focused on the soluble polymers and oligopeptides in solution; studies of investigation of signal transduction pathways that regulate entry conformations of dendrimers, star copolymers and polymers HIGHLIGHTS (continued) ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH with ionomers in dilute solution and modelling conformations inflammatory disease. Chronic inflammatory disease of the and dynamics of nucleic acids and polypeptides and kinetics of intestine causes a major health and financial burden on society protein folding. with current treatment being limited to symptomatic relief. An understanding of the underlying causes of chronic inflammation Dr. Noel Fitzpatrick has taught and researched in UCD since 1974. will lead to more effective therapeutics relieving these burdens His research interests include molecular orbital calculations, on individual patients and on society. molecular modelling of metal containing systems of medicinal interest, syntheses and spectroscopy of zinc hydroxamate Dr. David McHugh complexes. Dr. McHugh, Dept. of Animal Science & Production and Centre for Integrative Biology, was awarded a five-year Science Foundation Dr. Matthias Tacke joined UCD as a lecturer in 1996. His research Ireland (SFI) Investigator Programme Grant entitled: Analysis of interests include chemical synthesis, spectroscopy and structure mammalian physiological and genetic regulatory networks using determination. cDNA microarrays.
Professor Rory More O’Ferrall joined UCD in 1970, is Professor of Using bovine cDNA microarrays capable of monitoring gene Chemistry and has acted as Head of Department. His research expression and function in a massively parallel fashion across interests include ring-opening of the thiazolidine ring of penicillins, thousands of genes related to immune function, this group are carbocations from microbial oxidation products of aromatic trying to develop novel approaches to combating serious diseases hydrocarbons and acid-base and metal ion catalysis of that constraint cattle production. They will initially target bovine tautomerisation of heterocyclic ketones. tuberculosis, a bacterial infection and African trypanosomiasis (bovine sleeping sickness), a blood-borne parasitic disease. Dr. Wilhelm Risse has been a college lecturer in UCD since 1991. His research interests include the synthesis of bioactive molecules, The programme involves collaboration with a number of research cancer biology and advanced carbohydrate-based therapeutics. groups from the United States, Britain, France and Africa. The institutions involved include Michigan State University, the Roslin PROGRAMME GRANT AWARDS Institute and the International Livestock Research Institute in Kenya. Dr. Emmeline Hill from the Genetics Department, TCD has During the reporting period, many Conway Investigators were been appointed as senior postdoctoral scientist for this awarded major grants. Science Foundation Ireland investigator research programme. grants, each worth approximately 21 million over four years, were awarded to Dr. David McHugh, Dr. Alex Evans and Dr. Pat Lonergan, Dr. Alex Evans & Dr. Pat Lonergan Dr. Seamas Donnelly, Dr. Cormac Taylor, Dr. Geraldine Butler and Drs. Evans and Lonergan, Dept. of Animal Science & Production Dr. Wim Meijer. Dr. Therese Kinsella received a Wellcome Trust and Centre for Integrative Biology, were jointly awarded a five- programme grant of equivalent value. year Science Foundation Ireland (SFI) Investigator Programme Grant entitled: Functional genomics of tissue development in Dr. Cormac Taylor reproduction. Dr. Taylor, Dept. of Medicine & Therapeutics and Centre for Molecular Medicine, was awarded a five-year Science Foundation There has been a significant decline in fertility in recent years due Ireland (SFI) Investigator Programme Grant entitled: Impact to a number of factors in different species. The primary benefits of hypoxia on cAMP - dependent pro-inflamatory gene expression of the proposed research under this SFI award will be to increase in epithelial cells. our knowledge of the cellular and molecular factors that impact on reproduction. Specifically it will improve our understanding of Molecular oxygen is the primary source of metabolic energy for all the basic mechanisms controlling follicle growth, oocyte and eukaryotic cells. Hypoxia occurs when the cellular demand embryo development and the establishment of pregnancy. With for oxygen necessary to maintain physiological function exceeds this increase in knowledge, it will be possible to design strategies the supply delivered by the bloodstream due to diminished blood to more effectively control many or all of these processes for the flow (ischemia). purposes of fertility enhancement or contraception.
Recently it has been demonstrated that tissue ischemia / hypoxia Through the use of established models and local and international is associated with a number of chronic inflammatory diseases of collaboration, gene expression will be monitored in reproductive mucosal organs such as the intestine (e.g. Crohn’s disease). tissues using suppressive subtractive hybridisation, DNA microarray Furthermore, tissue hypoxia contributes to ongoing inflammation and real-time RT-PCR. The true functionality of genes will then be through the induction of pro-inflammatory genes such as TNFa. tested in well-defined in vivo and in vitro model systems. These events are dependent upon the targeted degradation of the cAMP-dependent transcription factor CREB. This project will identify the genes controlling the selection of the dominant/ ovulatory follicle, the acquisition of developmental ELEVEN We hypothesise that the mechanisms underlying CREB regulation competence by the oocyte and the growth of an embryo of sufficient in hypoxia are important therapeutic targets in ischemic / quality to establish a pregnancy and produce live offspring. HIGHLIGHTS (continued) ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH Dr. Geraldine Butler Dr. Seamus Donnelly Dr. Butler, Dept. of Biochemistry and Centre for Molecular Medicine, Dr. Donnelly, Dept. of Medicine & Therapeutics and Centre for was awarded a five-year Science Foundation Ireland (SFI) Molecular Medicine, was awarded a five-year Science Foundation Investigator Programme Grant entitled: Genomic Analysis of Ireland (SFI) Investigator Programme Grant entitled: Macrophage Biofilm Formation by the Pathogenic Yeast, Candida Parapsilosis. migration inhibitory factor (MIF), aberrant remodelling/repair & chronic inflammation. An emerging species of yeast, Candida parapsilosis is causing increasing numbers of infections because it spreads easily from Dr. Donnelly is the first physician-scientist to be awarded an medical devices into the blood stream of patients. As the yeast Investigator Programme Grant by Science Foundation Ireland. grows on the plastic surface of catheters, heart valves or Working in St. Vincent’s University Hospital and The Conway intravenous lines, it forms a thin film called a biofilm, which is Institute of Biomolecular and Biomedical Research, University difficult to destroy even with antifungal drugs. Infection with yeast College Dublin, Dr. Donnelly takes his first-hand experience of can be life threatening in newborn babies, the elderly or any patient clinical medicine to the laboratory bench in an effort to find answers whose immune system is not strong enough to fight the bacteria. to the problem of pulmonary fibrosis. In many cases, the only treatment choice involves first removing the medical device itself. Pulmonary fibrosis affects 5 million people worldwide each year. The same numbers of people die from pulmonary fibrosis as Up until now the majority of research has focused on Candida breast cancer. The disease is generally seen in people over the albicans but a recent worldwide study has shown that almost half age of fifty. The tissue in the lungs becomes inflamed initially of all yeast infections are caused by other species of yeast. As the and then, over time, will steadily become stiffened, or fibrosed. first research group to study C. parapsilosis at a detailed molecular When the lungs cannot work effectively, it becomes more difficult level, Dr. Butler and her team will first try to uncover the genetic to breathe. makeup of this yeast and then use this information to design in- house genetic techniques to investigate how the yeast grows on Over the four years of this grant, Dr. Seamus Donnelly and his team the surfaces of medical devices. This will increase the current will look at the process of inflammation that happens in the lung. understanding of the nature of the organism and pave the way for This may allow targeted treatment of the disease in the future. the development of potential drug targets. Dr. Therese Kinsella Dr. Wim Meijer Dr. Kinsella, Dept. of Biochemistry and Centre for Molecular Dr. Meijer, Dept. of Industrial Microbiology and Centre for Molecular Medicine, is an expert in the area of vascular thrombosis. Her Medicine, was awarded a five-year Science Foundation Ireland expertise was recognised recently when she became the first (SFI) Investigator Programme Grant entitled: A novel virulence member of academic staff in University College Dublin to be mechanism of the intracellular pathogen Rhodococcus equi. awarded a Wellcome Trust programme grant entitled: Mechanisms & Regulations of Intracellular sugnalling by the Thromboxanne A2 Although many microbial infections can be treated with existing and Prostacyclin receptors. antimicrobial drugs, it is becoming clear that many pathogens are no longer susceptible to established treatment procedures. The The grant, which is worth 21 million over five years, will allow Dr. development of novel treatment methods is dependent on a clear Kinsella and her team to continue their research into the way in understanding of the mechanisms employed by pathogens to cause which two lipid mediators in particular work. Thromboxane and disease. The aim of this project is to analyse the virulence prostacyclin are the Ying and Yang of the blood system. They play mechanism of R. equi, a pathogen of foals and an opportunistic important but opposing roles in the delicate balancing act that human pathogen. occurs in our bloodstream. Platelets are the cells in the blood that clump together to form a clot. Thromboxane promotes clot Rhodococcus equi is an intracellular pathogen of macrophages, formation by stimulating the platelets to clump while prostacyclin infecting young foals and immunocompromised humans. It survives prevents their clumping. inside macrophages by preventing phagosomal lysosomal maturation via an unknown process. The ability of this pathogen Winner of the Royal Irish Academy Award Medal for Biochemistry to cause disease is dependent on a large plasmid that encodes a in 2000, Dr. Kinsella is delighted “to be able to expand the group vital part of the virulence mechanism. However, many of the on the basis of the award, which will give us a broader base to proteins that are encoded by this plasmid are unique to R. equi, advance our investigations”. Dr. Therese Kinsella is keenly suggesting that this pathogen employs a novel virulence mechanism. anticipating the benefits that working in the multi-disciplinary setting of the Conway Institute will bring to her research. She says The aim of this project is to provide a framework to understand “our research at the molecular level would benefit from links with the biological function of the proteins encoded by the virulence people on the physiological and medical side who would be
TWELVE plasmid, based on their physical interactions with other proteins interested in the therapeutic possibilities arising from our work”. and subcellular localisation, role in virulence and effects on macrophage physiology.
HIGHLIGHTS (continued) ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH HIGH IMPACT PUBLICATIONS O’Donovan N, Crown J, Stunell H, Hill ADK, McDermott E, O’Higgins N, Duffy MJ. Caspase 3 in breast cancer Clinical Cancer Research Despite its limitations, we have used the impact factor; a 2003;9:738-742. [5.991] quantitative tool for ranking, evaluating, categorising, and comparing journals, in an effort to identify significant publications. Kiely B, Feldman G, Ryan MP Modulation of renal epithelial barrier It is clear that potentially significant papers may appear in journals function by mitogen- activated protein kinases (MAPKs): which are widely regarded as the best in the field but still have Mechanism of cyclosporine A- induced increase in transepithelial relatively low impact factors. The publications listed below are the resistance. Kidney International 2003;63:908-916 [5.016] top five publications by impact factor in each of the three Conway centres. A complete listing of the publications during the report Centre for Molecular Medicine period is given in Appendix 2. The impact factor of each journal [in parentheses] was calculated using the ISI Journal Citation Murphy BM, O’Neill AJ, Adrain C, Watson RWG, Martin SJ. The Reports®: Science Edition 2002 apoptosome pathway to caspase activation in primary human Neutrophils exhibits dramatically reduced requirements for Centre for Synthesis & Chemical Biology cytochrome c. Journal of Experimental Medicine 2003;197:625- 632. [15.837] Coleman, C. M.; O’Shea, D. F. New organolithium addition methodology to diversely functionalized indoles. Journal of the Drumm B, Vaughan D. Granulocyte-macrophage colony-stimulating American Chemical Society. 2003 125 (14): 4054-4055. [6.201] factor for Crohn’s disease. Lancet 2003;361:1830. [15.397]
McCormack, A. C.; McDonnell, C. M.; O’Ferrall, R. A. M.; O’Donoghue, Goh J, Godson C, Brady HR, MacMathuna P. Lipoxins: Pro-resolution A. C.; Rao, S. N. Protonated benzofuran, anthracene, naphthalene, lipid mediators in intestinal inflammation. Gastroenterology benzene, ethene, and ethyne: Measurements and estimates of 2003;124:1043-1054 [13.44] pK(a) and pK(R). Journal of the American Chemical Society 2002 124 (29): 8575-8583. [6.201] Wong S, Butler G, Wolfe KH. Gene order evolution and paleopolyploidy in hemiascomycete yeasts. Proc. Natl. Acad. Sci. Alkorta, I.; Rozas, I.; Elguero, J. Interaction of anions with perfluoro USA 99 (14): 9272-9277 Jul 9 2002 [10.896] aromatic compounds. Journal of the American Chemical Society 2002, 124 (29): 8593-8598. [6.201] Comerford KM, Leonard MO, Karhausen J, Carey R, Colgan SP, Taylor CT. Small ubiquitin-related modifier-1 modification Reid, G. D.; Whittaker, D J.; Day, M. A.; Turton, D. A.; Kayser, V.; mediates resolution of CREB-dependent responses to hypoxia. Kelly, J.M.; Beddard, G. S. Femtosecond electron-transfer reactions Proc. Natl. Acad. Sci. USA [10.7] in mono- and polynucleotides and in DNA. Journal of the American Chemical Society 2002, 124 (19): 5518-5527. [6.201]
Gunnlaugsson, T.; Davies, R. J. H.; Nieuwenhuyzen, M.; Stevenson, C. S.; Viguier, R.; Mulready, S. Rapid hydrolytic cleavage of the mRNA model compound HPNP by glycine based macrocyclic lanthanide ribonuclease mimics. Chemical Communication 2002, (18): 2136-2137. [4.038]
Centre for Integrative Biology
McBean GJ. Cerebral cystine uptake: a tale of two transporters. Trends in Pharmacological Sciences 23 (7): 299 – 302 Jul 2002 [11.394]
Allen LT, Fox EJP, Blute I, Kelly ZD, Rochev Y, Keenan AK, Dawson KA, Gallagher WM. “Interaction of soft condensed materials with living cells: Phenotype/transcriptome correlations for the hydrophobic effect”. Proc. Natl. Acad. Sci. USA 2003;100:6331- 6336. [10.7]
Kane R, Murtagh J, Finlay D, Marti A, Jaggi R, Blatchford D, Wilde C, Martin F. Transcription factor NFIC undergoes N-glycosylation FOURTEEN during early mammary gland involution. Journal of Biological Chemistry 277 (29): 25893-25903 Jul 19 2002 [7.258] CENTRE REPORTS > ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH CENTRE FOR SYNTHESIS AND CHEMICAL BIOLOGY The initiation of the CSCB-Regensburg Erasmus exchange scheme has had a positive effect on the graduate school. To date, six graduate students from Regensburg have visited the CSCB and five CSCB graduate students have been to Regensburg. The CSCB has recruited close to 60 new Ph.D. students and 20 postdoctoral fellows in the report period.
DUBLIN MOLECULAR MEDICINE CENTRE The Centre for Synthesis & Chemical Biology was awarded 226 million in Cycle 3 (2001-6) of the Higher Education Authority’s Programme for Research in Third Level Institutions (PRTLI). The CSCB assembles thirty-seven researchers in the chemical sciences from University College Dublin (UCD), Trinity College Dublin (TCD) and the Royal College of Surgeons in Ireland (RCSI). Within the spectrum of a ‘molecules to medicine’ approach to biomedical research, the design, synthesis and analysis of components is carried out by investigators within the CSCB. The biological testing The Dublin Molecular Medicine Centre is a unique partnership is done in collaboration within the Conway Institute at UCD, the between University College Dublin and Trinity College Dublin, the Dublin Molecular Medicine Centre (DMMC) at both UCD and TCD, activities of which are carried out at the Conway Institute of and the Biopharmaceutical Sciences Network (BSN) at the RCSI. Biomolecular and Biomedical Research and the Institute of External collaborations, both national and international, add value Molecular Medicine respectively. Through the Programme for to the research effort at each level of the programme elements. Human Genomics, complementary research is being carried out at the Royal College of Surgeons in Ireland. Scientists at these premier The three interrelated themes being developed are: biomedical research institutions are united through the DMMC with patient-focused clinicians working in the leading teaching hospitals • Bioactive Molecule Synthesis (Beaumont Hospital, Mater Misericordiae University Hospital, Our Involving the synthesis of molecules for biological and clinical Lady’s Hospital for Sick Children, Crumlin, St James’s Hospital, St evaluation and for the study of biological processes Vincent’s University Hospital and the Adelaide & Meath incorporating National Children’s Hospital, Tallaght). • Synthetic, Biosynthetic Methodology, Process Development This aims to develop the chemical and biochemical synthetic These trans-institutional partnerships focus on improving our methodologies in order to enable the preparation of target understanding of the origin and nature of commonly acquired compounds human diseases by exploiting developments in genomics and proteomic technologies. The genomics revolution allows scientists • Analytical, Structural & Computational Chemistry to better study the molecular mechanisms that contribute to This helps to suggest new drug leads for synthesis, gives greater dysfunction at a cellular level. This knowledge allows us to identify understanding of fundamental biochemical processes and the those groups of individuals who are most susceptible to particular analytical capability to underpin the research programme diseases, examine the interplay between genetic and environmental factors, detect disease onset at an earlier stage and develop sophisticated therapeutic responses. The DMMC accelerates the Highlights translation of fundamental molecular research to clinical applications resulting in improved patient healthcare. Appointments Dr Ed Irving, former Head of Central Research at Novartis, UK was DMMC is creating a repository of tissue samples, genetic material appointed as the Director of the CSCB in July 2003 and Mr. John with genotypic and phenotypic data that allows researchers to Brown has filled the position of Project & Financial Manager. evaluate specific clinical hypotheses. This national resource draws Professor Michael McGlinchey was appointed Professor of Inorganic on the close patient-consultant relationship and strong post- Chemistry in September 2002 and Dr Peter Rutledge has taken up operative follow-up that is a unique feature of Irish healthcare. a position as a lecturer in chemical biology. DMMC has also assembled key technology architecture in bioinformatics, functional genomics, proteomics, animal models, Education & Learning imaging and nanotechnologies. This modern infrastructure The official launch of the CSCB took place after the symposium on facilitates the education and training of a large pool of scientists December 17th 2002 and was officiated at by the UCD President, that will fuel the emerging Irish biopharmaceutical industry. Dr. Art Cosgrove, the Provost of TCD and the Chief Executive of
the RCSI. The inaugural symposium, entitled “Recent Advances in Research FIFTEEN Synthesis and Chemical Biology”, was well received with lectures Biomedical research at Dublin Molecular Medicine Centre is focused from six renowned international speakers. on four research areas: CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH ANNUAL REPORT 2003 SIXTEEN CENTRE REPORTS (continued) ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH Vascular Biology Education & Learning Objectives • Functional Genomics and Proteomics Of Vascular Disease DMMC continues to promote the dissemination of knowledge • Endothelial and Platelet Function throughout the research community through focused seminars • Angiogenesis and lecturers. 120 scientists attended a tri-institutional symposium highlighting DMMC research activities in the newly opened Durkan Inflammation & Host Defense institute of Molecular Medicine on June 23rd 2003. • Autoimmunity (Multiple Sclerosis,Rheumatoid Arthritis) • Infectious Diseases A comprehensive cross-institutional education and training programme in Molecular Medicine that broadens the training and Cancer research experience of students, priming them for careers in the • Colorectal & Oesophageal burgeoning Irish biosciences sector is being developed. The first • Breast & Prostate stage is the development of a series of taught courses and training • Haematological Malignancy modules that will work in conjunction with the existing research • Gynaecological Cancers degree courses in each institution. Postgraduate students will complete a number of optional courses grouped into three areas: Neuropsychiatric Diseases research/disease area oriented; technology oriented and • Alzheimer ’s Disease management/business oriented. Courses will be open courses to • Schizophrenia postdoctoral, technical, academic, and clinical staff to develop a • Bipolar Affective Disorder career-long training path. • Autism • Attention Deficit Hyperactivity Disorder DMMC Website The DMMC website, www.dmmc.ie, has been designed as a one- Highlights stop information resource for those wanting to know about DMMC related research, education, and events. The website will illustrate Appointments the collaboration of RCSI, TCD, UCD and affiliated hospitals in DMMC During the report period, Dr Pierre Meulien was appointed as Chief research and education, and detail the state-of-the-art core Executive of the DMMC. Dr Meulien was formerly Head of R&D at technologies available. It will provide information on research Aventis Pasteur, Canada. He has recruited a core DMMC Executive teams, funding, partnerships with industry, publications, and comprising: - entrepreneurial ventures.
• Executive Assistant : Ms Carmel Ní Luanaí • Financial Controller : Mr Peter O’Hara • Programme Manager : Mr Paul Harkin • Education Officer : Dr Mark Watson
Dr L Patrick Gage, formerly Head of Global Research at Wyeth Pharmaceuticals has been appointed as Chairman to the Board of Directors. Academic representation on the Board includes Dr Desmond Fitzgerald, Royal College of Surgeons in Ireland and industrial representation on the board has been increased with the appointment of Barry O’Leary (Divisional Manager, Pharmaceuticals & Biotechnology, IDA Ireland) and Ronan O’Caoimh (Chairman & Chief Executive, Trinity Biotech). SEVENTEEN CONWAY INSTITUTE TODAY > ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH AN INNOVATIVE RESEARCH BUILDING The academic year 2002/2003 saw the pilot introduction of the Conway Academic Programme for Graduate Students. This The innovative design of the Conway Institute itself contributes programme has a core Conway curriculum component, links into to promoting interaction between research groups with large, existing postgraduate courses available to all postgraduates in open-plan research laboratories and shared support facilities. The UCD and will ultimately have components from each of the Conway central provision of office, writing, meeting and social spaces is an centres. The pilot programme introduced the molecular medicine essential feature in facilitating the interdisciplinary mission of the component of the continuum. Institute. A new teaching facility, which incorporates laboratories and classrooms, forms an integral part of the new building providing In liaison with representatives of postgraduate education a premier educational environment for undergraduate students committees in Trinity College and the Royal College of Surgeons in life sciences. This will ensure that students are embedded in the in Ireland, the Conway and DMMC are currently developing the research milieu from an early stage and that Conway Institute programme for postgraduate research students in the academic graduates will be well equipped for careers in the expanding year 2003/2004. This will see the expansion of the core curriculum knowledge-based bioindustry and healthcare sectors. with lectures from expert researchers from across the three institutions and further development of key elements of this core curriculum through the delivery of advanced courses. TECHNOLOGY In order to promote innovation and technology transfer among academics, postdoctoral fellows and postgraduate students, a The following core technology platforms are now fully equipped, series of lectures entitled “The Journey of the Entrepreneur-From staffed and operational within the Conway Institute: Research to Commercial Success” was organised by the University • Affymetrix GeneChip oligonucleotide arrays Industry Programme, in conjunction with the Conway Institute and Professor Frank Roche, Berber Family Chair of • Real-Time Polymerase Chain Reaction [PCR] Entrepreneurship, Graduate School of Business. Following the • Confocal microscopy and imaging success of the lecture series, a new module by NovaUCD entitled • Laser capture microdissection “Intellectual Property for Biotechnology” will be incorporated into • Biological Nuclear Magnetic Resonance [NMR] the postgraduate education programme for 2003/2004.
The following technologies will come on-stream in the coming DISCIPLINE INTEGRATION AND TECHNOLOGY year: TRANSFER SEMINAR SERIES • Flow cytometry and cell sorting [FACS] The first Conway Festival of Research was held in September 2001 • Transgenic facility and marked the start of a high-level Discipline Integration and • Proteomics facility Technology Transfer Seminar Series. A seminar is held each month between October and June featuring a highly noted external EDUCATION PROGRAMME scientific speaker, two internal Conway speakers (Principal Investigator and post doctoral fellow) representing one of the Undergraduate Teaching seven Conway research themes and a lecture on various aspects A key part of the Conway mission is to enhance the quality and of technology transfer. The four defined biomedical areas of the scope of the undergraduate experience of the departments Conway research programme host afternoon sessions while the associated with the Institute. To this end, the facilities for three centres host symposia; day long events encompassing the undergraduate students have been incorporated into the new breadth of research being carried out within the three centres of Conway building. These students will benefit from state-of-the- the Conway Institute. art teaching laboratories and lecture facilities and most, if not all, will do their 4th year research projects with Conway investigators. The organisation of the Discipline Integration and Technology The wider undergraduate student body in the five sponsoring Transfer Seminar Series is the responsibility of the Conway Seminar faculties will benefit from the active research experience of Committee. The incoming chairperson for the 2003/2004 series lecturers who are also Conway Investigators. Students will have is Dr. Gethin McBean. She takes over from Dr. R. William Watson access to Conway core technologies through their supervisors and who has completed two years in this role. We extend our thanks are encouraged to attend Conway Institute Discipline Integration to Dr. R. William Watson for his hard work and dedication during and Technology Transfer seminars. this time. Dr. McBean and the committee will address how the current format of the series can be developed with the opening of Postgraduate Education the new institute building. The Conway Institute takes a holistic approach to the issue of postgraduate education. A culture of excellence in research is The seminars are open to all researchers from postgraduate supported by generic induction courses, discipline or centre-specific students to academics. Indeed, in order to broaden the appeal of
EIGHTEEN courses, aspects of publishing and commercialisation as well as the 2002/2003 seminar series, a particular effort was made to the Conway core curriculum. The latter provides training in modules include lectures from researchers at different levels in their career. such good laboratory practice, data presentation skills and bioethics. The seminars are widely advertised in the various centres of the CONWAY INSTITUTE TODAY (continued) ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH Conway, associated institutions and hospitals as well as throughout TECHNOLOGY TRANSFER AND the biotechnology sector and on the Conway web site. COMMERCIALISATION
During the 2002/2003 series, the official launch of the Centre for The Conway Institute places particular emphasis on fostering Synthesis and Chemical Biology took place during their symposium entrepreneurship within University College Dublin and creating on December 17th. The Centre for Integrative Biology held their strong partnerships with industry. Working closely with NovaUCD spring symposium in February 2003 and the symposium of the and Bioresearch Ireland, the Conway Institute ensures that Dublin Molecular Medicine Centre was hosted by Trinity College this researchers have access to support services for continuing year in their newly opened Durkan Institute of Molecular Medicine. professional education, practical business advice and incubation A full listing of lectures in the Discipline Integration & Technology facilities to assist in the establishment and development of campus Transfer Series 2002/2003 can be found in Appendix 4. companies. This proactive policy for the translation of research has seen many of the principal investigators within the Conway INFORMATION Institute establishing links with the biotechnology and pharmaceutical sectors through collaborative programmes, Research Information System contract research and campus companies. The Research Information System is a web based research management tool that will capture the expertise of the academic staff, postdoctoral fellows and postgraduate students within the university. University College Dublin worked extensively with the UK based vendor, InfoEd to customise the software in order to adapt the existing terminology to suit the Irish university situation. It is being implemented throughout University College Dublin on a phased basis and the Conway Institute was chosen as one of two pilot sites.
The Conway Board of Management recognise the importance of access to high quality research information as a management tool and have stated that all Conway investigators must regularly update their research profiles. On July 1st 2003, InterTradeIreland and the Conference of the Heads of Irish Universities launched expertiseireland.com, which is populated by the Research Information System. This web based and searchable portal will capture the research expertise that exists in all of Ireland, north and south.
COMMUNICATION
In order to secure funding, it is vital that the work of the Conway Institute is communicated to the government, funding bodies and the general public. During the reporting period, articles about the scientific research being carried out by Conway investigators have been published in national broadsheets, specialised journals, college publications and on national radio. The coming year will be an opportunity to build on the momentum gathered from the publicity surrounding the opening of the Conway Institute and to constantly remind the stakeholders, not only of the excellent research being done currently, but the exciting potential of collaborative, multi- disciplinary research. NINETEEN CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH ANNUAL REPORT 2003 TWENTY CONTACT US > ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH Directorate Conway Institute of Biomolecular and Biomedical Research University College Dublin Belfield, Dublin 4, Ireland Tel: (+353 1) 716 6700 Fax: (+353 1) 716 6701 Email: [email protected] Web: www.ucd.ie/conway
Director Dr. Philip Nolan Tel: (+353 1) 716 6702 Email: [email protected]
Personal Assistant to Director Ms. Ashling Gantly Tel: (+353 1) 716 6702 Email: [email protected]
Assistant Director, Buildings & Technical Services Mr. Michael O’Sullivan Tel: (+353 1) 716 6705 Email: [email protected]
Business and Finance Manager Mr. Peter Mangan Tel: (+353 1) 716 6704 Email: [email protected]
Communications & Education Officer Ms. Elaine Quinn Tel: (+353 1) 716 6706 Email: [email protected]
Receptionist/Executive Assistant Ms. Verona Patchell Tel: (+353 1) 716 6700 Email: [email protected]
Executive Assistant (Information & Education) Ms. Ciara O’Hanlon Tel: (+353 1) 716 6720 Email: [email protected]
Getting Here The Conway Institute of Biomolecular & Biomedical Research is located on the Belfield campus of University College Dublin, 4 miles south of Dublin city centre on the N11. Access to the college from the N11 is via the Belfield flyover. TWENTYONE APPENDIX I >Listing of grant awards during report period ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH CONWAY PROJECT TITLE CENTRE
CIB Analysis of Mammalian Physiological and genetic regulatory networks using cDNA microarrams CIB SFI: Functional genomics of tissue development in reproduction CIB Strategic Development of disease - modifying drugs for the treatment of dementia CIB Gene Therapy Approaches to Human Disease in Pre-Clinical Models CIB Isolation and purification of azaspiracids from naturally contaminated materials and evaluation of their toxic effects CIB BSE in Sheep CIB The DNA damage checkpoint and cancer CIB Apoptosis during early development in Xenopus embryos - a role for the p53 tumor suppressor protein CIB Sheep AI using frozen thawed semen
CIB Adaption of environment sensitive hydrogels to local delivery of potential anti-testonosis theraphy CIB Identification of a novel pro-inflammatory Signalling Molecule in the Brain CIB Professor C.L. Vaughan. Understanding the Role of the Brain in Fatigue CIB Development of Ruminant Embryos CIB Immunodiagnostics I or Emerging animal & human Parasitic disease (IDEP) CIB Functional and Morphological Maintenance of Mammary Epithelial Structures by the Combined Action of Extracellular Matrix Components and Glucocorticoids :Studies on a Novel Cell Culture Model System CIB Gene - Specific Silencing of PrP Expression by Small Interfering RNAs CIB Exploring the role of PRISM in Inflammatory signalling pathways CIB CIB Molecular analysis of gene expression patterns in the terminal and lbud of the developing mammary gland CIB Angiogenesis in the pulmonary circulation: Pathogenetic role in chronic lung infection CIB Prognostic significance of bone marrow micrometastases in breast cancer CIB Orphan Nuclear Receptor Function in Human Inflammatory Joint Disease CIB The function of the BMP antogonist gremlin in the developing ventebrake kidney CIB An investigation of ZO-1 and Occludin at the blood retinal barrier CIB Transcriptional regulation of survivin in breast cancer. CIB Molecular mechanisms in breast cancer resistance to hormone therapy CIB Molecular mechanisms of breast cancer resistance to anti-estrogen therapy -a biological / clinical study CIB Evaluation of the biological activity of novel structural analogues of 3,4 - methylenedioxymethamphetamine (MDMA) and its potential metabolities CIB Effects of alcholol on prenatal development of the cerebellum CIB Long term effects of caffine on Synaptic Plastcity and Implicit Memory CIB The Feline blood brain barrier in health and disease CIB Molecular control of neural crest cell migration and survival in the developing hindgut. CIB Genomic & Proteomic approaches to the control of emerging + re-emerging infectious diseases - Fasciola Hepatics CIB CIB CIB Coregulator alterations in Tamoxifen resistance CIB Elucidation of objective indicators of stress using a comparative functional genomics approach CIB Control of bovine respiratory disease (BRD) through development of improved vaccinations using viral cDNA based antigens CIB An Investigation of the Blood Retinal Barrier Permeability Properties CIB CIB Molecular mechanisms of survivin Regulations in Breast Cancer CIB Association between Scrapie genotype & growth & carcass traits in sheep CIB Streptococcus Mutans adherence to hydroxyapatite beads and its prevention CIB Enhanced endothelial protection and repair in prophylaxis of restenosis injury CIB Elucidation of objective indicators of stress using a comparative functional genomics approach CIB Role of Co-regulators in estrogen receptors Function CIB The role of nuclear co-regulatory proteins in estrogen receptor function CIB Temporal and spatial distribution of PrPBSE in BSE infected transgenic mice expressing bovine PrP and experimentally infected cattle and its potential for diagnosis CIB The role of Rho/ROCK in the vascular remodelling in chronically hypoxic lungs TWENTYTWO CMM Impact of hypoxia on cAMP - dependent pro-inflamatory gene expression in epithelial cells. CMM A novel virulence mechanism of the intracellular pathogen Rhodococcus equi: protein networks, their role in virulence and impact on macrophage physiology CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH TWENTYTHREE ANNUAL REPORT 2003 Maurice Boland CO-APPLICANT PRINCIPAL APPLICANT Health Research Board Paul McLoughlin FUNDING AGENCY ) 2 1135500 951555 484040 404723 Foundation Ireland Science 353853 246000 Science Foundation Ireland 201139 Enterprise Ireland 181932 HEA/PRTLI Cycle 3 180000 Marine Institute European Commission FP5 Health Research Board IRCSET Dept. of Agriculture, Food & Rural Development David MacHugh Alex Evans Alex Evans Ciaran Regan Torres Sweeney Paul McLoughlin Pat Lonergan Finian Martin Michael Ryan Pat Lonergan, Hensey Carmel 89405 89405 89405 73000 63838 HEA/PRTLI Cycle 3 57150 HEA/PRTLI Cycle 3 57150 HEA/PRTLI Cycle 3 49700 Children’s Hospital Research Foundation 45000 Science Foundation Ireland 45000 IRCSET Postgraduate Research Scholarship 43000 IRCSET Postgraduate Research Scholarship 33022 Royal College of Surgeons in Ireland 30500 Teagasc 30000 Bannigan John 19750 Teagasc Finian Martin Fighting Blindness 17776 Michael Ryan IRCSET Postgraduate Research Scholarship 15000 Cancer Research Ireland John Bannigan 9000 Teagasc Prem Puri Kathy O'Boyle 6348 Grace Mulcahy Health Research Board Arnold Hill Sean Callanan Irish Heart Foundation Kathy O'Boyle Teagasc UCD In-House Schemes in Support of Research 1527500 Royal College of Surgeons 900416 Dept. Agriculture, Food and Rural Development Science Foundation Ireland Leonie Young Science Foundation Ireland Brenda Brankin Leonie Young Mark Crowe Rogers Mark Cliona O'Farrelly Mark Crowe Alan Keenan Leonie Young Torres Sweeney Brian McKenna Cormac Taylor Mark Crowe Wim Meijer CONTRACT TOTAL ( 152000 151000 150000 144000 124200 Science Foundation Ireland 123000 Health Research Board 115000 HEA- PRTLI 112888 IRCSET 112000 Health Research Board 97000 Group American College of Surgeons Oncology 91790 Health Research Board 91790 European Commission FP5 89405 Fighting Blindness Arnold Hill Cancer Research Ireland Mark Rogers St Luke’s Institute for Cancer Research St. Luke's Institute of Cancer Research HEA/PRTLI Cycle 3 Paul Moynagh Paul McLoughlin Arnold Hill Maurice Boland Carmel Hensey Evelyn Murphy Young Leonie Martin Finian Arnold Hill Brenda Brankin Pat Lonergan Gethin McBean 170806 162398 159914 159509 153500 Health Research Board 153000 HEA/PRTLI Cycle 3 Science Foundation Ireland HEA/PRTLI Cycle 3 Enterprise Ireland Health Research Board Alan Keenan Mark O'Malley Paul Moynagh Maurice Boland Finian Martin Grace Mulcahy APPENDIX I APPENDIX (continued) APPENDIX I (continued) ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH CONWAY PROJECT TITLE CENTRE
CMM Macrophage migration inhibitory factor (MIF), aberrant remodelling/repair & chronic inflammation CMM Mechanisms & Regulations of Intracellular sugnalling by the Thromboxanne A2 and Prostacyclin receptors. CMM Molecular cytogenetic and gene expression profiling studies of neuroblastoma
CMM Production of human disease-specific oligonucleotide microarrays, and transcriptional profiling of infectious and inflammatory disease
CMM Development of an animal model of neurotrauma CMM Cell-biomaterial interactions: an integrated view using gene expression profiling CMM Computational, biomechanical and biochemical studies of blunt head impact trauma CMM Malignant melanoma: functional studies using DNA methyltransferase inhibitors and genetic suppressor element technology CMM Adaptation of environment-sensitive hydrogels to local delivery of potential anti-restenosis
CMM Determining the mechanisms whereby TnF modulates glutamate-induced currents and long-term potentiation in single granule cells CMM Determination of factors controlling biocompatibility CMM Regulation of insulin secretion from perfused pancreatic beta cell lines CMM Hypoxia-elicited p-glycoprotein expression: potential role in chemotherapeutic resistance CMM Mechanism of Action of Neuropeptide Regulation of Synaptic Transmission in the Nucleus Accumbens: The Action of Acute and Chronic Psychostimulants CMM An investigation of the potential antifibrotic actions of lipoxins in renal cells CMM Electrophysiological and biochemical investigation of the cyclo oxygenase 2 (COX 2) - Signalling pathway in Hippocampal Synaptic plasticity CMM Molecular mechanisms of Tubulointertitial Fibrosis in Diabetic Mephropathy CMM Protein tyrosine phosphatases in human melanoma genesis, a functional study using genetic suppressor elements
CMM Investigation of the role of the calcium (Ca2+) dependent on Ca2+ independent/ Rho A pathways in thromboxane receptor (TP) signalling within the vasculature. ranscriptomic and proteomic approaches for the study of the intestinal epithelial CMM response to Helicobacter pylori soluble components in an ex vivo model for duodenal ulcerogenesis
CMM Strategies for use of alternative iron sources by the intracellular pathogen Rhodococcus equi CMM Nutrient, Hormone and Sulphonylurea regulation of metabolic/ secretory pathway and gene expression in pancreatic B-Cells CMM Genomic analysis of the transcriptional response of human macrophage cells to infection with the pathogenic yeast Candida albicans CMM Role of ADAMS in Breast Cancer CMM Mechanisims of action and therapeutic action and therapeutic petential of lipoxins in renal disease CMM Biological and Clinical Studies in Suicidal Depression CMM Evolution of avolve in primary cultures cells CMM Functional & Computational qenomics CMM Determining the mechanisms by which TNF Alpha modulates Synaptic Plasticity - electrophysiology CMM An investigation of a range of amphetamines to probe the neural circuitry of intact conscious brain for new sites of intervention in the treatment of Schizophrenia. CMM A Study of frontotemporal lemantia & Parkinson's disease in Ireland CMM Functional Genomics of breast cancer : A focus on Metastasis CMM Bioinformatics for the integration of gene expression and proteomics data in cancer
CMM Novel compounds for photodynamic therapy: Design, synthesis, in vitro evaluation and mechanistic studies
TWENTYFOUR CMM Cell-biomaterial interaction: an integrated view using gene expression profiling CMM Protein tyrosine phosphatases in human melanoma genesis, a functional study using Genetic Suppressor Elements. CMM The effects of diethylmaleate on the treatment strategies of prostate cancer in an in vivo animal model APPENDIX I (continued) ANNUAL REPORT 2003 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH CONTRACT FUNDING AGENCY PRINCIPAL CO-APPLICANT TOTAL (2) APPLICANT
898150 Science Foundation Ireland Seamas Donnelly 788872 Wellcome Trust Therese Kinsella 208000 Children’s Research Centre William Gallagher Ray Stallings, Michael McDermott, Ann O’ Meara, Fin Breatnach, William Gallagher 190000 Enterprise Ireland William Gallagher Geraldine Butler, Wim Meijer and Finian Martin 190000 IRCSET William T. O'Connor Dr. M. Gilchrist 189000 Enterprise Ireland William Gallagher Kenneth Dawson 180028 HEA/PRTLI Cycle 3 William T. O'Connor Dr. M.Gilchrist 171410 Health Research Board William Gallagher Dr. David Easty 165500 Health Research Board William Gallagher Alan Keenan and Kenneth Dawson 165307 HEA/PRTLI Cycle 3 John O'Connor
164000 Health Research Board William Gallagher Kenneth Dawson 163136 Enterprise Ireland Philip Newsholme 163021 Health Research Board Katrina Comerford 162398 HEA/PRTLI Cycle 3 Caroline Herron
160760 Health Research Board Catherine Godson 159423 IRCSET Caroline Herron
159018 Health Research Board Hugh Brady 158000 Cancer Research Ireland William Gallagher David J. Easty and Peter Dervan 157806 Health Research Board Therese Kinsella
155000 Health Research Board William Gallagher Dermot Kelleher, Ana Terres 154804 Enterprise Ireland Wim Meijer 149000 Health Research Board Philip Newsholme 142200 Health Research Board Geraldine Butler
107600 Health Research Board Michael J. Duffy 100000 Health Research Board Catherine Godson 100000 Mater Foundation Kevin Malone 96800 Glaxo Smith Kline Bill Watson 96000 Health Research Board Hugh Brady 95119 HEA/PRTLI Cycle 3 John O'Connor 92028 HEA/PRTLI Cycle 3 William T. O'Connor
89405 HEA/PRTLI Cycle 3 Hugh Brady 83791 Cancer Research Ireland William Gallagher Michael Duffy 83340 Enterprise Ireland William Gallagher Desmond Higgins and Aedin Culhane 72000 Association for International Cancer Research William Gallagher Donal O’ Shea 57150 IRCSET Postgraduate Research Scholarship Michael J. Duffy 57150 IRCSET Postgraduate Research Scholarship Michael J. Duffy 57150 IRCSET Postgraduate Research Scholarship William Gallagher TWENTYFIVE 51147 Cancer Research Ireland David Easty 38219 British Urological Foundation Bill Watson APPENDIX I (continued) NULRPR 2003 REPORT ANNUAL CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH CONWAY PROJECT TITLE CENTRE
CMM Characterisation of the altered apoptotic phenotype during basal prostate epithelial cell differentiation into luminal cells CMM Survival in Breast Cancer CMM Life in the Lion's Den : Effects of the intracellular pathogen Phodococcus equi on macrophage gene expression CMM A role for fibulin-4 in angiogenesis? CMM Mater College Bladder Microarray Study. CMM Improving Vaccination in early life CMM Molecular Determinants of Melanoma Progression CMM Adhesion in C. Albicans CMM Use of genetic suppressor elements to study melanoma invasion CMM NAS complement to Quality in molecular genetic testing: Development of certified reference materials. CMM Cell-Biomaterial Interactions CSCB CHIROCAT Chiral Catalysts by combinational chemistry CSCB Versatile Novel Biocatalysts for Pharma Synthon Production
CSCB Novel membranes for high temperature separation of CO2 from combustion exhaust gases CSCB Versatile Novel Biocatalysts for Pharma Synthon Production CSCB New photodynamic Therapeutic agents for the treatments of cancerous tumours CSCB Development of new multi-component reactions for combinational library generation CSCB Synthesis and Evaluation of RESTRICTED divalent Ligmo CSCB Synthesis and evaluation of signal transduction modulators CSCB Biosynthesis of epoxides using a whole cell biocatalyst
CSCB Versatile Novel Biocatalysts for Pharma Synthon Production CSCB A study of electronic and steric effects in axially chiral P-N ligands for asymmetric catalysis CSCB Complementary Carbohydrate molecules that self assemble in water CSCB Total Synthesis of Lipoxin A4 Analogues CSCB New Genocomplexes CSCB Design, synthesis and evaluation of Novel HIV inhibitors CSCB Scholarship CSCB Scholarship CSCB Studies in the Asymmetric Aldol CSCB Synthesis and NMR studies of 13C enriched inhibitors of the Thiol and Serine Proteases CSCB Scholarship CSCB CSCB CSCB CSCB CSCB CSCB CSCB Test potential asymmetric catalysts for carbon-carbon bond formation bynucleophilic addition of an organometallic reagent to a carbonyl-containingcompound. CSCB CSCB Test potential asymmetric catalysts for carbon-carbon bond formation bynucleophilic addition of an organometallic reagent to a carbonyl-containingcompound. CSCB CSCB MS Consumables CSCB Understanding the basis of NAD+/NADP+ Co-enzyme specificity CSCB CSCB On-/In-Line characterisation of bioprocess fluids using the focussed beam reflectance (FBRM) method CSCB Application of Heterobidentale Ligands in Asymmetrics Catalysis CSCB TWENTYSIX APPENDIX I (continued) ANNUAL REPORT 2003 CONWAY CONTRACT FUNDING AGENCY PRINCIPALRESEARCHER CO-APPLICANTCOAPPLICANT TOTAL (2) APPLICANTFULL NAME
INSTITUTE
36532 British Urological Foundation Bill Watson 33022 IRCSET Michael J. Duffy
OF
12697 Health Research Board Wim Meijer BIOMOLECULAR 9500 UCD William Gallagher 7618 Mater Misericordiae Hospital Peter Dervan 7256 European Commission FP5 Denis Reen 6450 Enterprise Ireland William Gallagher
&
4350 Enterprise Ireland Geraldine Butler BIOMEDICAL 2359 International Union Against Cancer David Easty 0 European Commission FP5 David Barton 0 Enterprise Ireland William Gallagher
449880 Enterprise Ireland Declan Gilheany RESEARCH 436000 Enterprise Ireland Paul Engel Brian Glennon, Patricia Kieran, Anita McGuire (UCC) 175356 IRCSET Donal MacElroy 156000 Enterprise Ireland Brian Glennon 154611 HEA/PRTLI Cycle 3 Donal O'Shea 154611 HEA/PRTLI Cycle 3 Donal O'Shea 154611 HEA/PRTLI Cycle 3 Paul Murphy 154611 HEA/PRTLI Cycle 3 Paul Murphy 148000 Enterprise Ireland Kevin O’Connor Patricia Kieran, Dermot Malone 140000 Enterprise Ireland Paul Engel 106880 IRCSET Patrick Guiry 92000 IRCSET Raphael Darcy 90600 HEA/PRTLI Cycle 3 Patrick Guiry 90600 HEA/ PRTLI Cycle 3 Raphael Darcy 83095 IRCSET Paul Murphy 64011 HEA/PRTLI Cycle 3 Michael Casey 64011 HEA/PRTLI Cycle 3 Patrick Caffrey 64011 HEA/PRTLI Cycle 3 Patrick Guiry 64011 HEA/PRTLI Cycle 3 Paul Malthouse 64011 HEA/ PRTLI Cycle 3 Stephen Mayhew 57150 IRCSET Postgraduate Research Scholarship Declan Gilheany 57150 IRCSET Postgraduate Research Scholarship Donal O'Shea 57150 IRCSET Postgraduate Research Scholarship Patrick Guiry 57150 IRCSET Postgraduate Research Scholarship Patrick Guiry 57150 IRCSET Postgraduate Research Scholarship Raphael Darcy 57150 IRCSET Postgraduate Research Scholarship Raphael Darcy 57150 IRCSET Research Scheme 2002 Declan Gilheany
33022 IRCSET Postgraduate Research Scholarship Declan Gilheany 33022 IRCSET Research Scheme 2002 Declan Gilheany
20687 IRCSET Postgraduate Research Scholarship Paul Murphy 20000 HEA/PRTLI Cycle 3 Donal O'Shea 19050 IRCSET Postgraduate Research Scholarship Paul Engel 16511 IRCSET Postgraduate Research Scholarship Patrick Guiry 9000 UCD Patricia Kieran Brian Glennon 6300 Enterprise Ireland Patrick Guiry 2500 Enterprise Ireland Patricia Kieran Dermot Malone (UCD),
Professor Andrew TWENTYSEVEN Daugulis, Canada CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH ANNUAL REPORT 2003 TWENTYEIGHT APPENDIX II >Listing of publications during report period ANNUAL REPORT 2003 CONWAY PEER REVIEWED PUBLICATIONS FROM 11. Bairead E, Harmon DL, Curtis AM, Kelly Y, O’Leary C, Gardner JULY 1ST 2002 – JUNE 31ST 2003 M, Leahy DT, Vaughan P, Keegan D, O’Morain C, O’Donoghue
D, Shanahan F, Parfrey NA, Quane KA. Association of NOD2 INSTITUTE 1. Aghajanian S, Worrall DM. Identification and characterization with Crohn’s disease in a homogenous Irish population. of the gene encoding the human phosphopantetheine European Journal of Human Genetics 2003;11:237-244.
adenylyltransferase and dephospho-CoA kinase bifunctional OF
12. Balding J, Kane D, Livingstone W, Mynett-Johnson L, BIOMOLECULAR enzyme (CoA synthase). Biochemical Journal 365: 13-18 Part Bresnihan B, Smith O, FitzGerald O. Cytokine gene 1 JUL 1 2002 polymorphisms - Association with psorlatic arthritis susceptibility and severity. Arthritis and Rheumatism 2. Aghajanian S, Hovsepyan M, Geoghegan KF, Chirunyk BA,
2003;48:1408-1413. &
Engel PC. A thermally sensitive loop in clostridial glutamate BIOMEDICAL dehydrogenase detected by limited proteolysis. Journal of 13. P. Barrett & B. Glennon, ‘Characterizing the Metastable Zone Biological Chemistry 2003;278:1067-1074. Width and Solubility Curve Using Lasentec FBRM and PVM’,
Chemical Engineering Research and Design, Transactions RESEARCH 3. Alexander MD, Traynor BJ, Miller N, Corr B, Frost E, McQuaid IChemE part A, 80, 799-805, October, 2002. S, Brett FM, Green A, Hardiman O. “True” sporadic ALS associated with a novel SOD-1 mutation. Annals of Neurology 14. Berry CB, McBean GJ. An investigation into the role of calcium 2002;52:680-683. in the modulation of rat synaptosomal D-[H-3]aspartate transport by docosahexaenoic acid. Brain Research 4. Allen LT, Fox EJP, Blute I, Kelly ZD, Rochev Y, Keenan AK, 2003;973:107-114. Dawson KA, Gallagher WM. Interaction of soft condensed materials with living cells: Phenotype/transcriptome 15. Boecker W, Moll R, Dervan P, Buerger H, Poremba C, Diallo correlations for the hydrophobic effect. Proc. Natl. Acad. Sci. RI, Herbst H, Schmidt A, Lerch MM, Buchwalow IB. Usual USA 2003; 100(3);100:6331-6336. ductal hyperplasia of the breast is a committed stem (progenitor) cell lesion distinct from atypical ductal 5. Appelbe Z, Casey M, Keaveney CM, Kelly CJ. A novel method hyperplasia and ductal carcinoma in situ. Journal of Pathology for the stereoselective synthesis of tetralins and indanes. 2002;198:458-467. Synlett 2002;1404-1408. 16. Brandt P, Norrby PA, Daly AM, Gilheany DG. Chromium - 6. Aparicio JF, Caffrey P, Gil JA, Zotchev SB. Polyene antibiotic Salen-mediated alkene epoxidation: A theoretical and biosynthesis gene clusters. Applied Microbiology and experimental study indicates the importance of spin-surface Biotechnology 2003;61:179-188. crossing and the presence of a discrete intermediate. Chemistry-A European Journal 2002;8:4299-4307. 7. Austin EJ, Mihm M, Evans ACO, Ireland JLH, Ireland JJ, Roche JF. Effects of oestradiol and progesterone on secretion of 17. Brazil DP, Park J and Hemmings BA (2002) PKB Binding gonadotrophins and health of first wave follicles during the Proteins: Getting in on the Akt. Cell 111:293-303. oestrous cycle of beef heifers. Reproduction 2002;124:531- 541. 18. Brennan L, Shine A, Hewage C, Malthouse JPG, Brindle KM, McClenaghan N, Flatt PR, Newsholme P. A nuclear magnetic 8. Bacon CL, Gallagher HC, Haughey JC, Regan CM. resonance-based demonstration of substantial oxidative L- Antiproliferative action of valproate is associated with alanine metabolism and L-alanine-enhanced glucose aberrant expression and nuclear translocation of cyclin D3 metabolism in a clonal pancreatic beta-cell line - Metabolism during the C6 glioma G1 phase. Journal of Neurochemistry of L-alanine is important to the regulation of insulin secretion. 2002;83:12-19. Diabetes 51 (6): 1714-1721 Jun 2002.
9. Bacurau RFP, O’Toole CE, Newsholme P, Rosa LFBP. Sub- 19. Brennan L, Hewage C, Malthouse JPG, McBean GJ. An NMR lethal concentrations of activated complement increase rat study of alterations in [1-C-13]glucose metabolism in C6 lymphocyte glutamine utilization and oxidation while lethal glioma cells by gliotoxic amino acids. Neurochemistry concentrations cause death by a mechanism involving ATP International 2003;42:441-448. depletion. Cell Biochemistry and Function 2002;20:183-190. 20. Bresnihan B, Cunnane G. Infection complications associated 10. Banningan AE, Watson RGW, Beddy D, Hurley H, Fitzpatrick with the use of biologic agents. Rheumatic Disease Clinics of JM, O’Connell PR. Increased adhesion molecule expression in North America 2003;29:185. serosal fibroblasts isolated from patients with inflammatory
bowel disease is secondary to inflammation. Ann. Surg. 235: 21. Bresnihan B, Roux-Lombard P, Murphy E, Kane D, FitzGerald TWENTYNINE 507-511. O, Dayer JM. Serum interleukin 18 and interleukin 18 binding protein in rheumatoid arthritis. Annals of the Rheumatic Diseases 61 (8): 726-729 AUG 2002. APPENDIX II (continued) NULRPR 2003 REPORT ANNUAL CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH 22. Bresnihan B. Rheumatoid arthritis: Principles of early 35. Castilla J, Adan AG, Brun A, Pintado B, Ramirez MA, Parra B, treatment. Journal of Rheumatology 2002;29:9-12. Doyle D, Rogers M, Salguero FJ, Sanchez C, Sanchez-Vizcaino JM, Torres JM. Early detection of PRPres in BSE-infected 23. Bresnihan B. Effects of anakinra on clinical and radiological bovine PrP transgenic mice. Archives of Virology outcomes in rheumatoid arthritis. Annals of the Rheumatic 2003;148:677-691. Diseases 2002;61:74-77. 36. Chertin B, Solari V, Reen DJ, Farkas A, Puri P. Up-regrulation 24. Bresnihan B. Anakinra as a new therapeutic option in of angiotensin-converting enzyme (ACE) gene expression rheumatoid arthritis: Clinical results and perspectives. Clinical induces tubulointerstitial injury in reflux nephropathy. and Experimental Rheumatology 2002;20:S32-S34. Pediatric Surgery International 2002;18:635-639.
25. Bresnihan B. Preventing joint damage as the best measure 37. Claessen, D, H.A.B. Wösten, G. van Keulen, O.G. Faber, A.M.C.R. of biologic drug therapy. Journal of Rheumatology 2002;29:39- Alves, W.G. Meijer, L. Dijkhuizen 2002. Two novel homologous 43. proteins of Streptomyces coelicolor and Streptomyces lividans are involved in formation of the rodlet layer and mediate 26. Brevini TAL, Lonergan P, Cillo F, Francisci C, Favetta LA, Fair attachment to a hydrophobic surface. Molecular Microbiology T, Gandolfi F. Evolution of mRNA polyadenylation between 44; 1483-1492. oocyte maturation and first embryonic cleavage in cattle and its relation with developmental competence. Molecular 38. Coffey RNT, Watson RWG, O’Neill AJ, Mc Eleny K, Fitzpatrick Reproduction and Development 2002;63:510-517. JM. Androgen-mediated resistance to apoptosis. Prostate 2002;53:300-309. 27. Broca C, Brennan L, Petit P, Newsholme P, Maechler P. (2003) Mitochondria-derived glutamate at the interplay between 39. Colgan SP, Taylor CT, Narravula S, Synnestvedt K, Blume ED. branched-chain amino acid and glucose-induced insulin Endothelial COX-2 induction by hypoxia liberates 6-keto-PGF1 secretion.FEBS Lett. 545(2-3):167-72. alpha, a potent epithelial secretagogue. Adv Exp Med Biol. 2002;507:107-12.
28. Brown DA, Errington W, Fitzpatrick NJ, Glass WK, Kemp TJ, 40. Collins C, Crowley D, Thunhurst C, Staines A, Bruen M, Magette Nimir H, Ryan A. A novel dizinc bridged hydroxamate model W, Malone D, Ryan M, Dean A, McMahon L. Waste for hydroxamate inhibited zinc hydrolases. Chem. Comm. management in Ireland. A qualitative study of the knowledge 2002: 1210- 1211. and attitudes of the public, industry and service providers. Epidemiology 13 (4): 964 JUL 2002 29. Bruynesteyn K, van der Heijde D, Boers M, Saudan A, Peloso P, Paulus H, Houben H, Griffiths B, Edmonds J, Bresnihan B, 41. Comerford KM, Leonard MO, Karhausen J, Carey R, Colgan Boonen A, van der Linden S. Detecting radiological changes SP, Taylor CT. Small ubiquitin-related modifier-1 modification in rheumatoid arthritis that are considered important by mediates resolution of CREB-dependent responses to hypoxia. clinical experts: Influence of reading with or without known Proc. Natl. Acad. Sci. USA 2003; 100(3);100:986-991. sequence. Journal of Rheumatology 2002;29:2306-2312.
42. Comerford, K.M., Leonard, M.O., Karhausen, J., Carey, R., 30. Bund SJ, Lee RMKW. The vascular amplifier and persisting Colgan, S.P. & Taylor C.T. SUMO-1 modification mediates resisters. Journal of Hypertension 2003;21:643-645. resolution of CREB-dependent responses to hypoxia. Proc. Natl. Acad. Sci. USA 2003; 100(3): 986-991. 31. Burke JG, Watson RWG, McCormack D, Dowling FE, Walsh MG, Fitzpatrick JM. Spontaneous production of monocyte 43. Conerney B, Jensen P, Kruger PE, MacGloinn C. The ‘Trinity’ chemoattractant protein-1 and interleukin-8 by the human helix: synthesis and structural characterisation of a C-3- lumbar intervertebral disc. SPINE 27 (13): 1402-1407 JUL 1 symmetric tris-bidentate ligand and its coordination to Ag(I). 2002. Chemical Communications 2003;1274-1275.
32. Butler MP, Moynagh PN, O’Connor JJ. Methods of detection 44. Cooke MM, McCarthy GM, Sallis JD, Morgan MP. Phosphocitrate of the transcription factor NF-kappa B in rat hippocampal inhibits calcium hydroxyapatite induced mitogenesis and slices. Journal of Neuroscience Methods 2002;119:185-190. upregulation of matrix metalloproteinase-1, interleukin-1 beta and cyclooxygenase-2 mRNA in human breast cancer cell lines. 33. Casey M, Keaveney CM, Walker AJ. MIRC reactions using Breast Cancer Research and Treatment 2003;79:253-263. sulfoxides and synthesis of dictyopterene A. Arkivoc 2002;91- 103. 45. Coughlan S, Connell J, Cohen B, Jin L, Hall WW. Suboptimal measles-mumps-rubella vaccination coverage facilitates an THIRTY 34. Casey M, Smyth MP. Ligand electronic effects in imported measles outbreak in Ireland. Clinical Infectious enantioselective diethylzinc additions. Synlett 2003;102-106. Diseases 35 (1): 84-86 JUL 1 2002. APPENDIX II (continued) ANNUAL REPORT 2003 CONWAY 46. Coyle AT, Miggin SM, Kinsella BT. Characterization of the 5’ 57. Daly AM, Gilheany DG. The synthesis and use in asymmetric untranslated region of alpha and beta isoforms of the human epoxidation of metal salen complexes derived from
thromboxane A2 receptor (TP). Differential promoter enantiopure trans-cyclopentane- and cyclobutane-1,2- INSTITUTE utilization by the TP isoforms. Eur J Biochem. 2002 diamine. Tetrahedron-Asymmetry 2003;14:127-137. Aug;269(16):4058-73.
58. de Chazal P, Heneghan C, Sheridan E, Reilly R, Nolan P, OF
47. M. C. Courtney, A.C. MacCormack and R.A. More O’Ferrall O’Malley M. Automated processing of the single-lead BIOMOLECULAR “Comparison of pKR values of Fluorenyl and Anthracenyl electrocardiogram for the detection of obstructive sleep Cations”, J. Phys. Org. Chem. 15, 529-539 (2002). apnoea. IEEE Trans Biomed Eng.2003 Jun; 50(6):686-96.
48. Crean CW, Kavanagh YT, O’Keeffe CM, Lawler MP, Stevenson 59. Deignan T, Curry MP, Doherty DG, Golden-Mason L, Volkov Y, &
BIOMEDICAL C, Davies RJH, Boyle PH, Kelly JM. Targeting of photooxidative Norris S, Nolan N, Traynor O, McEntee G, Hegarty JE, damage on single-stranded DNA representing the bcr-abl O’Farrelly C. Decrease in hepatic CD56(+) T cells and V alpha chimeric gene using oligonucleotide- conjugates containing 24(+) natural killer T cells in chronic hepatitis C viral infection.
[Ru(phen)(3)](2+)-like photosensitiser groups. Journal of Hepatology 37 (1): 101-108 JUL 2002 RESEARCH Photochemical & Photobiological Sciences 2002;1:1024-1033. 60. Devocelle M, McLoughlin BM, Sharkey CT, Fitzgerald DJ, Nolan 49. Cunningham D, Gallagher ET, Grayson DH, McArdle PJ, Storey KB. A convenient parallel synthesis of low molecular weight CB, Wilcock DJ. Synthesis and characterisation of a suite of hydroxamic acids using polymer-supported 1- four chiral pyridyl alcohols derived from (-)-menthol. Journal hydroxybenzotriazole. Organic & Biomolecular Chemistry of the Chemical Society-Perkin Transactions 1 2002;2692- 2003;1:850-853. 2698. 61. Dijkstra B, Healy C, Kelly LM, Mc Dermott EW, Hill ADK, 50. Cunningham J, Sales M, Pearce A, Howard J, Stallings R, O’Higgins NJ. Parathyroid localisation - current practice. J R Telford N, Wilkie R, Huntly B, Thomas A, O’Marcaigh A, Will Coll Surg Edinb. 2002; 47 (4): 599-607. A, Pratt N. Does isochromosome 7q mandate bone marrow transplant in children with Shwachman-Diamond syndrome? 62. Dijkstra B, Hill ADK, McDermott EW, O’Higgins N. Reduced British Journal of Haematology 2002;119:1062-1069. use of drains following axillary lymphadenectomy for breast cancer. ANZ J Surg 2003; 73 (4): 253. 51. Cunningham D, Grayson DH, McArdle P, Walsh JJ. The bromination of (-)-camphorquinone. Tetrahedron- 63. Donohue R, Mazzaglia A, Ravoo BJ, Darcy R. Cationic beta- Asymmetry 2003;14:1197-1200. cyclodextrin bilayer vesicles. Chemical Communications 2002;2864-2865. 52. Curran, B. & O’Connor, J.J. (2003). The inhibition of long- term potentiation by pro-inflammatory cytokines is attenuated 64. Dooley CM, Devocelle M, McLoughlin B, Nolan KB, Fitzgerald in the presence of nicotine. Neuroscience Letters, 344, 103- DJ, Sharkey CT. A novel family of hydroxamate-based 106. acylating inhibitors of cyclooxygenase. Molecular Pharmacology 2003;63:450-455. 53. Curran, B.P., Murray, H. & O’Connor, J.J. (2003). A role for c- jun n-terminal kinase in the inhibition of long-term 65. Doorty KB, Golubeva TA, Gorelov AV, Rochev YA, Allen LT, potentiation by IL-1b and long-term depression in the rat Dawson KA, Gallagher WM, Keenan AK. Poly(N- dentate gyrus in vitro. Neuroscience, 118, 347-357. isopropylacrylamide) co-polymer films as potential vehicles for delivery of an antimitotic agent to vascular smooth muscle 54. Curry MP, Golden-Mason L, Doherty DG, Deignan T, Norris S, cells. Cardiovascular Pathology 2003;12:105-110. Duffy M, Nolan N, Hall W, Hegarty JE, O’Farrelly C. Expansion of innate CD5(pos) B cells expressing high levels of CD81 in 66. Dowdall JF, Winter DC, Baird AW, Bouchier-Hayes D. hepatitis C virus infected liver. Journal of Hepatology Biological role and clinical implications of mast cells in surgery. 2003;38:642-650. Surgery. 2002 Jul;132(1):1-4.
55. Dardonville C, Rozas I, Goya P, Giron R, Goicoechea C, Martin 67. Drumm B, Vaughan D. Granulocyte-macrophage colony- MI. Synthesis and analgesic activity of a series of new azaalkane stimulating factor for Crohn’s disease. Lancet 2003;361:1830. bis-guanidinium and bis(2-aminoimidazolinium) compounds. Bioorganic & Medicinal Chemistry 2003;11:1283-1291. 68. Duff M, Ettarh RR. Crypt cell production rate in the small intestine of the zinc- supplemented mouse. Cells Tissues 56. Dalton CT, Ryan KM, Langan IJ, Coyne EJ, Gilheany DG. Organs 2002;172:21-28. THIRTYONE Asymmetric alkene epoxidation with chromium oxo salen complexes - Effect of pi-rich and other types of additives. 69. Duff T, Carter S, Feldman G, McEwan G, Pfaller W, Rhodes P, Journal of Molecular Catalysis A-Chemical 2002;187:179-187. Ryan M, Hawksworth G. Transepithelial resistance and inulin APPENDIX II (continued) NULRPR 2003 REPORT ANNUAL CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH permeability as endpoints in in vitro nephrotoxicity testing. girl with clinical features of MLS syndrome. Pediatric Atla-Alternatives to Laboratory Animals 2002;30:53-59. Dermatology 2003;20:153-157.
70. Duffy MJ, Lynn DJ, Lloyd AT, O’Shea CM. The ADAMs family 81. Evans ACO, O’Keeffe P, Mihm M, Roche JF, Macmillan KL, of proteins: from basic studies to potential clinical applications. Boland MP. Effect of oestradiol benzoate given after Thrombosis and Haemostasis 2003;89:622-631. prostaglandin at two stages of follicle wave development on oestrus synchronisation, the LH surge and ovulation in heifers. 71. Duffy MJ, van Dalen A, Haglund C, Hansson L, Klapdor R, Animal Reproduction Science 2003;76:13-23. Lamerz R, Nilsson O, Sturgeon C, Topolcan O. Clinical utility of biochemical markers in colorectal cancer: European Group 82. Fair T, Hyttel P, Motlik J, Boland M, Lonergan P. Maintenance on Tumour Markers (EGTM) guidelines. European Journal of of meiotic arrest in bovine oocytes in vitro using butyrolactone Cancer 2003;39:718-727. I: Effects on oocyte ultrastructure and nucleolus function. Molecular Reproduction and Development 62 (3): 375-386 72. Duffy M, Salemi M, Sheehy N, Vandamme AM, Hegarty J, JUL 2002. Curry M, Nolan N, Kelleher D, McKiernan S, Hall WW. Comparative rates of nucleotide sequence variation in the 83. Frantz K, Harte M, Ungerstedt U, O’ Connor WT. A dual probe hypervariable region of E1/E2 and the NS5b region of characterisation of dialysate amino acid levels in the medial hepatitis C virus in patients with a spectrum of liver disease prefrontal cortex and the ventral tegmental area in intact resulting from a common source of infection. Virology conscious rat brain. J Neuroscience Methods. 119 109-119 2002;301:354-364. Part 2 July 2002.
73. Duffy MJ. Urokinase plasminogen activator and its inhibitor, 84. Freir DB, Herron CE. Inhibition of L-type voltage dependent PAI-1, as prognostic markers in breast cancer: From pilot to calcium channels causes impairment of long-term potentiation level I evidence studies. Clinical Chemistry 48 (8): 1194-1197 in the hippocampal CA1 region in vivo. Brain Research AUG 2002. 2003;967:27-36.
74. Dunne JP, Bockmeyer M, Tacke M, Cocondensation Reactions 85. Freir D.B, Costello D.A and Herron C.E. A beta 25-35-induced of Substituted Aromatic Compounds with Lithium Atoms at depression of long-term potentiation in area CA1 in vivo and 77 K Eur. J. Inorg. Chem., 2003, 458 - 466. in vitro is attenuated by verapamil. J Neurophysiol. (2003) 89 :3061-9. 75. Dunne JP, Tacke M, Aryl Calcium Hydrides as Precursors to Alkoxides and Aryloxides of Calcium Eur. J. Inorg. Chem., 86. Freir D.B and Herron C.E. Nicotine enhances the depressive 2003, 1416 - 1425. actions of A beta 1-40 on long-term potentiation in the rat hippocampal CA1 region in vivo. J Neurophysiol. (2003) 76. Dyer J, Blau WJ, Coates CG, Creely CM, Gavey JD, George 89:2917-22. MW, Grills DC, Hudson S, Kelly JM, Matousek P, McGarvey JJ, McMaster J, Parker AW, Towrie M, Weinstein JA. The 87. S. Fox, J. P. Dunne, R. Dronskowski, D. Schmitz, M. Tacke photophysics of fac-[Re(CO)(3)(dppz)(py)](+) in CH3CN: a Synthesis and Structural Characterisation of a Novel Chiral comparative picosecond flash photolysis, transient infrared, ansa-Cobaltocenium Hexafluorophospate. Eur. J. Inorg. Chem., transient resonance Raman and density functional theoretical 2002, 3039 - 3046. study. Photochemical & Photobiological Sciences 2003;2:542- 554. 88. Gallagher ET, Grayson DH. Reactions of lithiated (E)-3-halo- 77. Earley, B. and Crowe, MA (2002). Effects of ketoprofen alone 1-phenylsulfonylprop-1-enes and (Z)-1-halo-3- or in combination with local anesthesia during castration of phenylsulfonylprop-1-enes with aldehydes. Organic & bull calves on plasma haptoglobin, in-vitro interferon- Biomolecular Chemistry 2003;1:1374-1381. production, white blood cell numbers and animal performance. Journal of Animal Science 80: 1044-1052. 89. Galvin DJ, Watson RWG, O’Neill AJ, Coffey RT, Brady H, Gillespie JI, Fitzpatrick. Mechanical stretch alters human 78. English NJ, MacElroy JMD. Atomistic simulations of liquid bladder smooth muscle phenotype. Euro. Urol. 2002 1: (1) water using Lekner electrostatics. Molecular Physics 131. 2002;100:3753-3769. 90. Galvin DJ, Watson RWG, Gillespie JI, Brady H, Fitzpatrick 79. English NJ, MacElroy JMD. Molecular dynamics simulations JM. Mechanical stretch regulates cell survival in human bladder of microwave heating of water. Journal of Chemical Physics smooth muscle cells in vitro. American Journal of Physiology- 2003;118:1589-1592. Renal Physiology 2002;283:F1192-F1199. THIRTYTWO
80. Enright F, Campbell P, Stallings RL, Hall K, Green AJ, Sweeney 91. Gaffney M, McMorrow T, Slattery C, Watson A, Brady H, Ryan E, Barnes L, Watson R. Xp22.3 microdeletion in a 19-year-old MP. Cyclosporine A-induced transdifferentiation in renal
APPENDIX II (continued) NULRPR 2003 REPORT ANNUAL CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH tubular epithelial cells: Implications for renal fibrosis. Journal 102. Hanlon J, Monks E, Hughes C, Weavers E, Rogers M. of the American Society of Nephrology 2002;13:544A. Metallothionein in bovine spongiform encephalopathy. Journal of Comparative Pathology 2002;127:280-289. 92. Glover L, Quinn S, Ryan M, Pette D, Ohlendieck K. Supramolecular calsequestrin complex - Protein-protein 103. Harney S, O’Shea FD, FitzGerald O. Peptostreptococcal interactions in chronic low-frequency stimulated muscle, pericarditis complicating anti-tumour necrosis factor alpha postnatal development and ageing. European Journal of treatment in rheumatoid arthritis. Annals of the Rheumatic Biochemistry 2002;269:4607-4616. Diseases 61 (7): 653-654 JUL 2002
93. Goh J, Godson C, Brady HR, MacMathuna P. Lipoxins: Pro- 104. Hasegawa H, Tatsumi M, Ogawa-Goto K, Takahashi H, Kojima resolution lipid mediators in intestinal inflammation. A, Iwasaki T, Kurata T, Sata T, Takeuchi T, Sheehy N, Sawa H, Gastroenterology 2003;124:1043-1054. Nagashima K, Hall WW. Processing of the HTLV-II envelope precursor glycoprotein gp63 by furin is essential for cell fusion 94. Grayson DH, McCarthy U, Roycroft ED. Intramolecular acylative activity. Aids Research and Human Retroviruses 2002;18:1253- ring-switching reactions of 3- (tetrahydro-2 ’-furyl) propanoic 1260. acid derivatives to give butanolides: mechanism and scope. Organic & Biomolecular Chemistry 2003;1:1930-1937. 105. Healy C, B Dijkstra, LM Kelly, EW Mc Dermott, ADK Hill, NJ O’Higgins. Pregnancy associated breast cancer. Irish Medical 95. Greene LM, Twal WO, Duffy MJ, McDermott EW, Hill AD, Journal 2002; 95 (2): 51-2.. O’Higgins NJ, McCann A, Dervan P, Argraves W, Gallagher WM. Elevated expression and altered processing of fibulin- 106. Healy CE, B Dijkstra, M Walsh, ADK Hill, J Murphy. Nipple 1 protein in human breast cancer. British Journal of Cancer adenoma: A differential diagnosis for Paget’s disease. Breast 2003;88:871-878. J 2003, 9 (4): 325-6.
96. Gunnlaugsson T, Davies RJH, Nieuwenhuyzen M, O’Brien JE, 107. Healy DA, Watson RWG, Newsholme P. Polyunsaturated and Stevenson CS, Mulready S. Synthesis, structural and biological monounsaturated fatty acids increase neutral lipid evaluation of GlyAla based lanthanide macrocyclic conjugates accumulation, caspase activation and apoptosis in a neutrophil- as supramolecular ribonuclease mimics. Polyhedron like, differentiated HL-60 cell line. Clinical Science 2003;22:711-724. 2003;104:171-179.
97. Gunnlaugsson T, Leonard JP. Synthesis and evaluation of 108. Healy DA, Watson RWG, Newsholme P. Glucose, but not colorimetric chemosensors for monitoring sodium and glutamine, protects against spontaneous and anti-Fas potassium ions in the intracellular concentration range. antibody-induced apoptosis in human neutrophils. CLINICAL Journal of the Chemical Society-Perkin Transactions 2 SCIENCE 103 (2): 179-189 AUG 2002 2002;1980-1985. 109. Hegarty NJ, Watson RWG, Young LS, O’Neill AJ, Brady HR, 98. Gunnlaugsson T, O’Brien JE, Mulready S. Glycine-alanine Fitzpatrick JM Cytoprotective effects of nitrates in a cellular conjugated macrocyclic lanthanide ion complexes as artificial model of hydronephrosis. KIDNEY INT 62 (1): 70-77 JUL 2002 ribonucleases. Tetrahedron Letters 2002;43:8493-8497. 110. Hegarty NJ, Young LS, O’Neill AJ, Watson RWG, Fitzpatrick 99. Gunnlaugsson T, Harte AJ, Leonard JP, Nieuwenhuyzen M. JM. Endothelin in unilateral ureteral obstruction: Vascular Delayed lanthanide luminescence sensing of aromatic and cellular effects. Journal of Urology 2003;169:740-744. carboxylates using heptadentate triamide Tb(III) cyclen complexes: the recognition of salicylic acid in water. Chemical 111. Hegarty PK, Watson RWG, Coffey RNT, Webber MM, Communications 2002;2134-2135. Fitzpatrick JM. Effects of cyclic stretch on prostatic cells in culture. Journal of Urology 2002;168:2291-2295. 100. Gunnlaugsson T, Davies RJH, Nieuwenhuyzen M, Stevenson CS, Viguier R, Mulready S. Rapid hydrolytic cleavage of the 112. Henry MT, McMahon K, Mackarel AJ, Prikk K, Sorsa T, Maisi P, mRNA model compound HPNP by glycine based macrocyclic Sepper R, FitzGerald MX, O’Connor CM. Matrix lanthanide ribonuclease mimics. Chemical Communications metalloproteinases and tissue inhibitor of metalloproteinase- 2002;2136-2137. 1 in sarcoidosis and IPF. European Respiratory Journal 2002;20:1220-1227. 101. Gunnlaugsson T, Gunaratne HQN, Nieuwenhuyzen M, Leonard JP. Synthesis of functionalised macrocyclic compounds as 113. Henry MT, McMahon K, Costello C, Fitzgerald MX, O’Connor CM. Secretory leukocyte proteinase inhibitor and elafin are
THIRTYFOUR Na+ and K+ receptors: a mild and high yielding nitration in water of mono and bis 2-methoxyaniline functionalised crown resistant to degradation by MMP-8.Exp Lung Res. 2002 ethers. Journal of the Chemical Society-Perkin Transactions Mar;28(2):85-97. 1 2002;1954-1962. APPENDIX II (continued) ANNUAL REPORT 2003 CONWAY 114. Hensey C, Dolan V, Brady HR. The Xenopus pronephros as a 126. Kennedy SM, O’Driscoll L, Purcell R, Fitz-simons N, McDermott model system for the study of kidney development and EW, Hill AD, O’Higgins NJ, Parkinson M, Linehan R, Clynes M.
pathophysiology. Nephrology Dialysis Transplantation Prognostic importance of survivin in breast cancer. British INSTITUTE 2002;17:73-74. Journal of Cancer 2003;88:1077-1083.
115. Hooper SB, ADK Hill, S Kennedy, B Dijkstra, LM Kelly, EW 127. Kerins F, O’Shea DF. Generation of substituted styrenes via OF
McDermott, NJ O’Higgins. Tamoxifen as the primary treatment Suzuki cross-coupling of aryl halides with 2,4,6- BIOMOLECULAR in elderly patients with breast cancer. Irish Journal of Medical trivinylcyclotriboroxane. Journal of Organic Chemistry 67 Science 2002; 171 (1): 28-30 (14): 4968-4971 JUL 12 2002
116. Hopkins N, McLoughlin P. The structural basis of pulmonary 128. Keane MP, Donnelly SC, Belperio JA, Goodman RB, Dy M, &
BIOMEDICAL hypertension in chronic lung disease: remodelling, rarefaction Burdick MD, Fishbein MC, Strieter RM. Imbalance in the or angiogenesis? Journal of Anatomy 2002;201:335-348. expression of CXC chemokines correlates with bronchoalveolar lavage fluid angiogenic activity and procollagen levels in acute
117. Hopkins N, Cadogan E, Giles S, Bannigan J, McLoughlin P. respiratory distress syndrome. Journal of Immunology RESEARCH Type 2 nitric oxide synthase and protein nitration in chronic 2002;169:6515-6521. lung infection. Journal of Pathology 2003;199:122-129. 129. Keegan J, Kruger PE, Nieuwenhuyzen M, Martin N. Molecular box versus helicate: Selective synthesis of macrocyclic 118. Howell K, Hopkins N, McLoughlin P. Combined confocal [Cu2L2](2+) and helical [Cu2L3](4+) species. Crystal Growth microscopy and stereology: a highly efficient and unbiased & Design 2002;2:329-332. approach to quantitative structural measurement in tissues. Experimental Physiology 2002;87:747-756. 130. Kelly BD, Becker K, Kermode V, Stallings RL, Murphy RP, Green AJ, Hillery J. Dysmorphic features and learning 119. Howell K, Preston RJ, McLoughlin P. Chronic hypoxia causes disability in an adult male with pure partial trisomy 17q24- angiogenesis in addition to remodelling in the adult rat q25 due to a terminal duplication. American Journal of Medical pulmonary circulation. J Physiol 2003; 547(Pt 1):133-45. Genetics 2002;112:217-220.
120. Irwin JA, Lynch SV, Coughlan S, Baker PJ, Gudmundsson HM, 131. Kelley LP, Kinsella BT. The role of N-linked glycosylation in Alfredsson GA, Rice DW, Engel PC. Alanine dehydrogenase determining the surface expression, G protein interaction and from the psychrophilic bacterium strain PA-43: effector coupling of the alpha (alpha) isoform of the human overexpression, molecular characterization, and sequence thromboxane A(2) receptor. Biochim Biophys Acta. 2003 May analysis. Extremophiles 2003;7:135-143. 2;1621(2):192-203.
121. Jones JFX, O’Leary DM, Pickering M. (2003). Vagal control of 132. SM Kennedy, L O’Driscoll, R Purcell, N Fitzsimons, EW the cranial venae cavae of the rat heart. Experimental McDermott, ADK Hill, NJ O’Higgins, M Parkinson, R Linehan, Physiology: 88.3: 329-334. M Clynes. Prognostic importance of survivin in breast cancer. Br J Cancer 2003 88(7); 1077-1083. 122. Kane R, Murtagh J, Finlay D, Marti A, Jaggi R, Blatchford D, Wilde C, Martin F. Transcription factor NFIC undergoes N- 133. Kennelly MM, Geary M, McCaffrey N, McLoughlin P, Staines glycosylation during early mammary gland A, McKenna P. Exercise-related changes in umbilical and involution.JOURNAL OF BIOLOGICAL CHEMISTRY 277 (29): uterine artery waveforms as assessed by Doppler ultrasound 25893-25903 JUL 19 2002 scans. American Journal of Obstetrics and Gynecology 2002;187:661-666. 123. Kelley LP, Kinsella BT. The role of N-linked glycosylation in determining the surface expression, G protein interaction and 134. Kennelly MM, McCaffrey N, McLoughlin P, Lyons S, McKenna effector coupling of the alpha (alpha) isoform of the human P. Fetal heart rate response to strenuous maternal exercise: thromboxane A(2) receptor. Biochimica et Biophysica Acta- Not a predictor of fetal distress. American Journal of Obstetrics General Subjects 2003;1621:192-203. and Gynecology 2002;187:811-816.
124. Kelly GE, Thin A, Daly L, McLoughlin P. Estimation of the gas 135. Kiely D, Guiry PJ. A comparative study of diphosphine and exchange threshold in humans: a time series approach. Eur J phosphinamine palladium complexes on a new substrate for Appl Physiol 2002; 87(6):588. the intramolecular asymmetric Heck reaction. Tetrahedron Letters 2002;43:9545-9547. 125. Kelly SS, Glynn PM, Madden SJ, Grayson DH. Impurities in a morphine sulfate drug product identified as 5- 136. Kiely B, Feldman G, Ryan MP. Modulation of renal epithelial THIRTYFIVE (hydroxymethyl)-2-furfural, 10-hydroxymorphine and 10- barrier function by mitogen- activated protein kinases (MAPKs): oxomorphine. Journal of Pharmaceutical Sciences Mechanism of cyclosporine A- induced increase in transepithelial 2003;92:485-493. resistance. Kidney International 2003;63:908-916. CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH ANNUAL REPORT 2003 THIRTYSIX APPENDIX II (continued) ANNUAL REPORT 2003 CONWAY 137. Kilbride E, McLoughlin P, Gallagher CG, Harty HR. Do gender 148. Lonergan P, Faerge I, Hyttel PM, Boland M, Fair T. differences exist in the ventilatory response to progressive Ultrastructural modifications in bovine oocytes maintained
exercise in males and females of average fitness? Eur J Appl in meiotic arrest in vitro using roscovitine or butyrolactone. INSTITUTE Physiol 2003; 17:17 Molecular Reproduction and Development 2003;64:369-378.
138. Kilroy TG, Hennessy AJ, Connolly DJ, Malone YM, Farrell A, 149. Loughrey JPR, Laffey JG, Moore BJ, Lynch F, Boylan JF, OF
Guiry PJ. From 2,3-dihydrofuran to 2,2-dialkyl-2,3- McLoughlin P. Interleukin-1 beta rapidly inhibits aortic BIOMOLECULAR dihydrofurans: new substrates for the intermolecular endothelium- dependent relaxation by a DNA transcription- asymmetric Heck reaction. Journal of Molecular Catalysis A- dependent mechanism. Critical Care Medicine 2003;31:910- Chemical 2003;196:65-81. 915.
&
139. Killoran J, Allen L, Gallagher JF, Gallagher WM, O’Shea DF. 150. Lowther J, Djurdjevic-Pahl A, Hewage C, Malthouse JPG. A BIOMEDICAL Synthesis of BF2 chelates of tetraarylazadipyrromethenes C-13-NMR study of the inhibition of papain by a dipeptide- and evidence for their photodynamic therapeutic behaviour. glyoxal inhibitor. Biochemical Journal 2002;366:983-987.
Chemical Communications 2002;1862-1863. RESEARCH 151. Lynch A, Eckhard K, McMahon G, Wall R, Kane P, Nolan K, 140. Kunakbaeva Z, Carrasco R, Rozas I. An approximation to the Schuhmann W, Diamond D. Cation binding selectivity of mechanism of inhibition of cystein proteases: nucleophilic partially substituted calix[4]arene esters. Electroanalysis sulphur addition to Michael acceptors type compounds. Journal 2002;14:1397-1404. of Molecular Structure-Theochem 2003;626:209-216. 152. Lozano JM, Lonergan P, Boland MP, O’Callaghan D. Influence 141. Lappin DWP, McMahon R, Murphy M, Brady HR. Gremlin: an of nutrition on the effectiveness of superovulation example of the re-emergence of developmental programmes programmes in ewes: effect on oocyte quality and post- in diabetic nephropathy. Nephrology Dialysis Transplantation fertilization development. Reproduction 2003;125:543-553. 2002;17:65-67. 153. R Mofidi, R Walsh, PF Ridgeway, T Crotty, EW McDermott, TV 142. Lawlor PG, Lynch PB, Gardiner GE, Caffrey PJ, O’Doherty JV. Keaveny, MJ Duffy, ADK Hill, N O’Higgins. Objective Effect of liquid feeding weaned pigs on growth performance management of breast cancer oestrogen receptor status to harvest. Journal of Animal Science 80 (7): 1725-1735 through digital image analysis. Eur J Surg Oncol 2003; 29 (1): JUL 2002 20-4.
143. Lawlor PG, Lynch PB, Caffrey PJ, O’Doherty JV. Effect of pre- 154. Malone KM, Waternaux C, Haas GL, Cooper TB, Li SH, Mann and post-weaning management on subsequent pig JJ. Cigarette smoking, suicidal behavior, and serotonin performance to slaughter and carcass quality. Animal Science function in major psychiatric disorders. American Journal of 2002;75:245-256. Psychiatry 2003;160:773-779.
144. Leonard DS, Hill ADK, Kelly LM, Dijkstra B, McDermott EW, 155. Malthouse JPG. Stereo specificity of alpha-proton exchange O’Higgins N. Anti-human epidermal growth factor receptor 2 reactions catalysed by pyridoxal-5 ’-phosphate-dependent monoclonal antibody therapy for breast cancer. British Journal enzymes. Biochimica et Biophysica Acta-Proteins and of Surgery 2002; 89 (3): 262-71. Proteomics 2003;1647:138-142.
145. Leonard M.O., Cottell D.C., Godson C., Brady H.R. & Taylor 156. Markos, F., Campion, D.P., Carey, M. & O’Connor, J.J. (2002). C.T. The role of HIF-1alpha in transcriptional regulation of An investigation into the mechanism of action of almitrine on the proximal tubular epithelial cell response to hypoxia. J Biol isolated rat diaphragm muscle fatigue. Respiration, 69(4), Chem. 2003 Jul 28 [Epub ahead of print] 339-343.
146. Leonard, MO, Hannan, K., Burne, MJ, Doran, P., Coleman, P., 157. Martin DSD, Lonergan PE, Boland B, Fogarty MP, Brady M, Stenson, C., Taylor, CT, Daniel, F, Godson, C, Petasis, NA, Horrobin DF, Campbell VA, Lynch MA. Apoptotic changes in Rabb, H, Brady.HR. A synthetic analogue of 15-epi-lipoxin A4, the aged brain are triggered by interleukin-1 beta-induced is protective in experimental ischemic acute renal failure J activation of p38 and reversed by treatment with Am Soc Nephrol 2002;13(6):1657-62. eicosapentaenoic acid. Journal of Biological Chemistry 2002;277:34239-34246. 147. Liu X, Sood S, Liu H, Nolan P, Morrison JL, Horner RL. Suppression of genioglossus muscle tone and activity during 158. Mazzaglia A, Scolaro LM, Darcy R, Donohue R, Ravoo BJ. reflex hypercapnic stimulation by GABA(A) mechanisms at Entangled porphyrins in cyclodextrin vesicles. Journal of THIRTYSEVEN the hypoglossal motor nucleus in vivo. Neuroscience Inclusion Phenomena and Macrocyclic Chemistry 2002;44:127- 2003;116:249-259. 132. APPENDIX II (continued) NULRPR 2003 REPORT ANNUAL CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH 159. McBride RA, Kelly JM, McCormack DE. Growth of well-defined 171. McNicholas WT, Krieger J, ERS Task F. Public health and ZnO microparticles by hydroxide ion hydrolysis of zinc salts. medicolegal implications of sleep apnoea. European Journal of Materials Chemistry 2003;13:1196-1201. Respiratory Journal 2002; 20:1594-1609.
160. McBean GJ. Cerebral cystine uptake: a tale of two transporters. 172. Miggin SM, Kinsella BT. Investigation of the mechanisms of Trends in Pharmacological Sciences 23 (7): 299-302 JUL 2002 G protein: Effector coupling by the human and mouse prostacyclin receptors - Identification of critical species- 161. McDonald DGM, McMenamin JB, Farrell MA, Droogan O, Green dependent differences. Journal of Biological Chemistry 277 AJ. Familial childhood onset neuropathy and cirrhosis with (30): 27053-27064 JUL 26 2002 the 4977bp mitochondrial DNA deletion. American Journal of Medical Genetics 111 (2): 191-194 AUG 22 2002 173. Miggin SM, Lawler OA, Kinsella BT. Palmitoylation of the human prostacyclin receptor - Functional implications of 162. MacElroy JMD. Molecular simulation of the kinetic selectivity palmitoylation and isoprenylation. Journal of Biological of a model silica system Molecular Physics 100 (14): 2369- Chemistry 2003; 278:6947-6958. 2376 JUL 2002 174. Minnock P, FitzGerald O, Bresnihan B. Quality of life, social 163. McEvoy A., Bresnihan B, FitzGerald O and Murphy E. 2002. support, and knowledge of disease in women with rheumatoid Corticotropin-Releasing Hormone signaling in vascular arthritis. Arthritis & Rheumatism-Arthritis Care & Research endothelium is mediated through the cAMP/CREB pathway. 2003; 49:221-227. Annals New York Academy of Science 966, 119-130. 175. Minogue A.M, Schmid A.W, Fogarty M.P, Moore A.C, Campbell 164. McEvoy A, Conneely O.M., Bresnihan B., FitzGerald O and V.A, Herron C.E, Lynch M.A. Activation of the c-Jun N-terminal Murphy E. 2002. Activation of nuclear orphan receptor NURR1 kinase signaling cascade mediates the effect of amyloid-beta transcription by NFkB and CREB in rheumatoid arthritis on long term potentiation and cell death in hippocampus: a synovial tissue. Journal of Immunology 168, 2979-2987. role for interleukin-1beta? J Biol Chem. 2003 Jul 25; 278(30): 27971-80. Epub 2003 May 07. 165. McKone EF, Barry SC, FitzGerald MX, Gallagher CG. The role 176. Mihm M, Crowe MA, Knight PG, Austin EJ. Follicle wave growth of supplemental oxygen during submaximal exercise patients in cattle. Reproduction in Domestic Animals 37 (4): 191-200 with cystic fibrosis. European Respiratory Journal 20 (1): AUG 2002. 134-142 Jul 2002
177. M Mitas, K Mikhitarian, L Hoover, MA Lockett, L Kelly, ADK 166. Mckee V, Morgan GG. A perchlorate salt of an octaprotonated Hill, W Gillanders, DJ Cole. Prostate specific Ets (PSE) factor: cryptand. Acta Crystallographica Section C-Crystal Structure a novel marker for detection of metastatic breast cancer in Communications 2003;59:O150-O152. axillary lymph nodes. British Journal of Cancer 2002; 86 (6): 899-904. 167. McMahon B, Mitchell D, Shattock R, Martin F, Brady HR, Godson C. Lipoxin, leukotriene, and PDGF receptors cross- 178. Mitchell S, Thomas G, Harvey K, Cottell D, Reville K, Berlasconi talk to regulate mesangial cell proliferation. FASEB Journal G, Petasis NA, Erwig L, Rees AJ, Savill J, Brady HR, Godson C. 2002; 16:U136-U151. Lipoxins, aspirin-triggered epi-lipoxins, lipoxin stable analogues, and the resolution of inflammation: Stimulation of macrophage 168. Mc Manus TE, Moore JE, Crowe M, Dunbar K, Elborn JS. A phagocytosis of apoptotic neutrophils in vivo. Journal of the comparison of pulmonary exacerbations with single and American Society of Nephrology 2002;13:2497-2507. multiple organisms in patients with cystic fibrosis and chronic Burkholderia cepacia infection. Journal of Infection 2003; 179. Mofidi R, Walsh R, Ridgway PF, Crotty T, McDermott EW, 46:56-59. Keaveny TV, Duffy MJ, Hill ADK, O’Higgins N. Objective measurement of breast cancer oestrogen receptor status 169. McCarthy AA, Walsh MA, Verma CS, O’Connell DP, Reinhold through digital image analysis. European Journal of Surgical M, Yalloway GN, d’Arcy D, Higgins TM, Voordouw G, Mayhew Oncology 2003;29:20-24. SG. Crystallographic investigation of the role of aspartate 95 in the modulation of the redox potentials of Desulfovibrio 180. Montague AL, Markey BK, Bassett HF, Jones BR, Larkin H, vulgaris flavodoxin. Biochemistry 2002; 41:10950-10962. McAllister H, Quinn PJ. A study of greyhounds with tonsillar enlargement and a history of poor racing performance. 170. McManus HA, Guiry PJ. Coupling of bulky, electron-deficient Veterinary Journal 2002;164:106-115. partners in aryl amination in the preparation of tridentate bis(oxazoline) ligands for asymmetric catalysis. Journal of THIRTYEIGHT 181. Moran E, O’Keeffe M, O’Connor R, Larkin AM, Murphy P, Clynes Organic Chemistry 2002; 67:8566-8573. M. Methods for generation of monoclonal antibodies to the very small drug hapten, 5-benzimidazolecarboxylic acid. Journal of Immunological Methods 2002;271:65-75. APPENDIX II (continued) ANNUAL REPORT 2003 CONWAY 182. Morgan MP, Kennedy M, Cooke MM, McCarthy GM. Molecular 193. Newsholme, P., Procopio, J., Ramos Lima,M.M., Pithon-Curi, mechanisms of calcium hydroxyapatite crystal-induced T.C. and Curi R (2003): Glutamine and glutamate – their central
mitogenesis in breast cancer. Journal of Pathology role in cell metabolism and function. Cell Biochem. Funct. 21, INSTITUTE 2002;198:42A. 1-9.
183. Morrison JL, Sood S, Liu X, Liu HT, Park E, Nolan P, Horner 194. Newsholme, P., Ramos Lima M.M., Procopio, J., Pithon-Curi, OF
RL. Glycine at hypoglossal motor nucleus: genioglossus activity, T.C. Doi, S.Q., Bazotte, B. and Curi R (2003): Glutamine and BIOMOLECULAR CO2 responses, and the additive effects of GABA. Journal of glutamate as vital metabolites. Brazilian Journal of Medical Applied Physiology 2002;93:1786-1796. and Biological Research 36, 153-163.
184. Murphy A, Stephens J, McMonagle P, Hutchinson M, Parfrey 195. Nolan D, Darcy R, Ravoo BJ. Preparation of vesicles and &
BIOMEDICAL N, Byrne P. Sequence analysis of SPAST in Irish families with nanoparticles of amphiphilic cyclodextrins containing labile autosomal dominant hereditary spastic paraparesis. Journal disulfide bonds. Langmuir 2003;19:4469-4472. of Pathology 2002;198:43A.
196. Norris S, Doherty DG, Curry M, McEntee G, Traynor O, Hegarty RESEARCH 185. Murphy BM, O’Neill AJ, Adrain C, Watson RWG, Martin SJ. JE, O’Farrelly C. Selective reduction of natural killer cells and The apoptosome pathway to caspase activation in primary T cells expressing inhibitory receptors for MHC class I in the human Neutrophils exhibits dramatically reduced livers of patients with hepatic malignancy. Cancer Immunology requirements for cytochrome c. Journal of Experimental Immunotherapy 2003;52:53-58. Medicine 2003;197:625-632. 197. N Nugent, ADK Hill, M Casey, LM Kelly, B Dijkstra, CD Collins, EW McDermott, NJ O’Higgins. Safety guidelines for 186. Murphy E, FitzGerald O, Saxne T, Bresnihan B. Increased radiolocalised sentinel node resection. Irish Journal of Medical serum cartilage oligomeric matrix protein levels and Science 2002; 170 (4): 236-8. decreased patellar bone mineral density in patients with chondromalacia patellae. Annals of the Rheumatic Diseases 198. Nuki G, Bresnihan B, Bear MB, McCabe D. Long-term safety 2002;61:981-985. and maintenance of clinical improvement following treatment with anakinra (recombinant human interleukin-1 receptor 187. Murray, H. & O’Connor, J.J. (2003). A role for COX-2 and p38 antagonist) in patients with rheumatoid arthritis. Arthritis mitogen activated protein kinase in long-term depression in and Rheumatism 2002;46:2838-2846. the rat dentate gyrus in vitro. Neuropharmacology, 44, 374- 380. 199. O’Brien N, Maguire TM, O’Donovan N, Lynch N, Hill ADK, McDermott E, O’Higgins N, Duffy MJ. Mammaglobin A: A 188. Murphy M, McMahon R, Lappin DWP, Brady HR. Gremlins: Is promising marker for breast cancer. Clinical Chemistry 48 this what renal fibrogenesis has come to? Exp Nephrol 10 (4): (8): 1362-1364 AUG 2002. 241-244 2002
200. O’Connor K, B Dijkstra, L Kelly, E McDermott, ADK Hill, N 189. Murphy PV, Pitt N, O’Brien A, Enright PM, Dunne A, Wilson O’Higgins. Successful conservative management of SJ, Duane RM, O’Boyle KM. Identification of novel inhibitors neutropaenic enterocolotis: a report of two cases and a review of fibroblast growth factor (FGF-2) binding to heparin and of the literature. ANZ J Surg 2003 73 (6):463-5. endothelial cell survival from a structurally diverse carbohybrid library. Bioorganic & Medicinal Chemistry Letters 201. O’Connor TM, Casey M, Aherne T, Bredin CP. A smoker with an 2002;12:3287-3290. apical mass. Postgraduate Medical Journal 2002;78:629.
190. Murphy PV, McDonnell C, Hamig L, Paterson DE, Taylor RJK. 202. O’Doherty E, Healy A, Aherne M, Hanrahan JP, Weavers E, Confirmation of the structure of a glucono-1,4-lactone Doherty M, Roche JF, Gunn M, Sweeney T. Prion protein (PrP) derivative obtained from silylation of glucono-1,5-lactone. gene polymorphisms associated with natural scrapie cases Tetrahedron-Asymmetry 2003;14:79-85. and their flock-mates in Ireland. Research in Veterinary Science 2002;73:243-250. 191. Murphy PV, O’Brien JL, Gorey-Feret LJ, Smith AB. Structure- based design and synthesis of HIV-1 protease inhibitors 203. O’Donovan N, Crown J, Stunell H, Hill ADK, McDermott E, employing beta-D-mannopyranoside scaffolds.Bio-organic & O’Higgins N, Duffy MJ. Caspase 3 in breast cancer. Clinical Medicinal Chemistry Letters 12 (13): 1763-1766 JUL 8 2002 Cancer Research 2003;9:738-742.
192. Nemeth L, Rolle U, Reen DJ, Puri P. Nitrergic hyperinnervation 204. O’Neill RM, Hassan J, Reen DJ. IL-7-Regulated homeostatic THIRTYNINE in appendicitis and in appendices histologically classified as maintenance of recent thymic emigrants in association with normal. Archives of Pathology & Laboratory Medicine caspase-mediated cell proliferation and apoptotic cell death. 2003;127:573-578. Journal of Immunology 2003;170:4524-4531. APPENDIX II (continued) NULRPR 2003 REPORT ANNUAL CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH 205. O’Nuallain, B. and Mayhew S.G. (2002) A comparison of the malignant melanoma British Journal of Surgery 2002; 89 (4): urea-unfolding of apoflavodoxin and flavodoxin from 389-96. Desulfovibrio vulgaris, Eur. J. Biochem. 269, 212-223. 218. Pritchard RS, ADK Hill, B Dijkstra, EW McDermott, NJ 206. O’Meara B, Mulcahy G. A survey of helminth control practices O’Higgins. Prevention of breast cancer. Br J Surg 2003; 90 in equine establishments in Ireland. Veterinary Parasitology (7): 772-83. 2002;109:101-110. 219. RS Prichard, B Dijkstra, EW McDermott, ADK Hill, NJ O’Higgins. 207. O’Reilly SM, Moynagh PN. Regulation of toll-like receptor 4 The role of molecular staging in malignant melanoma. Eur J signalling by A20 zinc finger protein. Biochemical and Surg Oncol 2003, 29 (4): 306-14. Biophysical Research Communications 2003;303:586-593. 220. Rackard SM, Carr AJ, Callanan JJ, Bellenger CR. An avian 208. O’Shea C, N McKie, Y Buggy, C Duggan, ADK Hill, E Mc Dermott, model of limb deviation induced by periosteal surgery. N O’Higgins, MJ Duffy. Expression of ADAM-9 mRNA and protein Research in Veterinary Science 2002; 73:237-241. in human breast cancer. Int J Cancer 2003; 105 (6): 754-61. 221. Rahman, M. T., Herron, L. L., Kapur, V., Meijer, W. G., Byrne, 209. Oda Y, Wanders W, Huisman LA, Meijer WG, Gottschal JC, B. A., Ren, J., Nich olson, V. M., & Prescott, J. F. 2003. Overview Forney LJ. Genotypic and phenotypic diversity within species of a partial genome sequence of Rhodococcus equi ATCC of purple nonsulfur bacteria isolated from aquatic sediments. 33701. Veterinary Microbiology. 94; 143-158. Applied and Environmental Microbiology 68 (7): 3467-3477 222. Rizos D, Gutierrez-Adan A, Perez-Garnelo S, de la Fuente J, JUL 2002. Boland MP, Lonergan P. Bovine embryo culture in the presence or absence of serum: Implications for blastocyst 210. Papadopoulos S, Rizos D, Duffy P, Wade M, Quinn K, Boland development, cryotolerance, and messenger RNA expression. MP, Lonergan P. Embryo survival and recipient pregnancy Biology of Reproduction 2003;68:236-243. rates after transfer of fresh or vitrified, in vivo or in vitro produced ovine blastocysts. Animal Reproduction Science 223. Rizos D, Fair T, Papadopoulos S, Boland MP, Lonergan P. 2002;74:35-44. Developmental, qualitative, and ultrastructural differences between ovine and bovine embryos produced in vivo or in 211. Pearson, A. P. Glennon, B. Kieran, P. M (2003) ‘Comparison vitro. Molecular Reproduction and Development 62 (3): 320- of Morphological Characteristics of Streptomyces natalensis 327 JUL 2002. by Image Analysis and Focused Beam Reflectance Measurement’, Biotechnol. Prog. 19: 1342-1347. 224. Ryan S, McNicholas WT, O’Regan RG, Nolan P. Intralaryngeal neuroanatomy of the recurrent laryngeal nerve of the rabbit. 212. Peters M, Rozas I, Alkorta I, Elguero J. DNA triplexes: A study Journal of Anatomy 2003;202:421-430. of their hydrogen bonds. Journal of Physical Chemistry B 2003; 107:323-330. 225. Ryan S, McNicholas WT, O’Regan RG, Nolan P. Upper airway muscle paralysis reduces reflex upper airway motor response 213. Petersen A, Puschban Z, Lotharius J, NicNiocaill B, Wiekop P, to negative transmural pressure in rat. Journal of Applied O´Connor WT Brundin P. Evidence for dysfunction of the Physiology 2003;94:1307-1316. nigrostriatal pathway in the R6/1 line of transgenic Huntington’s disease mice. Neurobiology Disease 11 134-146 226. Savage D, Perkins J, Lim CH, Bund SJ. Functional evidence September 2002. that K+ is the non-nitric oxide, non- prostanoid endothelium- derived relaxing factor in rat femoral arteries. Vascular 214. Pfeil K, Eder EI, Bartsch G, O’Neill A, Watson R.W.G., Klocker Pharmacology 2003;40:23-28. H. Differences in the expression of Apoptosis-related proteins in LNCaP and Long-term androgen-ablated LNCaP Prostate 227. Said-Salim B, Dunman PM, McAleese FM, Macapagal D, Murphy cancer cells. Euro. Urol. 2002 1: (1) 54. E, McNamara PJ, Arvidson S, Foster TJ, Projan SJ, Kreiswirth BN. Global regulation of Staphylococcus aureus genes by rot. 215. Pickering M, Jones JFX. The diaphragm: two physiological Journal of Bacteriology 2003;185:610-619. muscles in one. Journal of Anatomy 2002;201:305-312. 228. Seah SYK, Britton KL, Rice DW, Asano Y, Engel PC. Single 216. Pithon-Curi TC, Schumacher RI, Freitas JJS, Lagranha C, amino acid substitution in Bacillus sphaericus phenylalanine Newsholme P, Palanch AC, Doi SQ, Curi R. Glutamine delays dehydrogenase dramatically increases its discrimination spontaneous apoptosis in neutrophils. American Journal of between phenylalanine and tyrosine substrates. Biochemistry Physiology-Cell Physiology 2003;284:C1355-C1361. 2002;41:11390-11397.
FORTY 217. Pritchard RS, ADK Hill, SJ Skehan, N O’Higgins. Positron 229. Shanahan EM, Ahern M, Smith M, Wetherall M, Bresnihan B, emission tomography for staging and management of FitzGerald O. Suprascapular nerve block (using bupivacaine
APPENDIX II (continued) NULRPR 2003 REPORT ANNUAL CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH and methylprednisolone acetate) in chronic shoulder pain. 241. Timoshenko EG, Kuznetsov YA. Improved Gaussian self- Annals of the Rheumatic Diseases 2003;62:400-406. consistent method - applications to homopolymers with different architectures in dilute solution. Journal of Chemical 230. Shaw C, O’Hanlon DM, O’Keane C, Kerin MJ. Malignant Physics 2002;117:5404-5414. phaeochromocytoma metastasising to the breast. Irish Journal of Medical Science 2003;172:41-42. 242. Timoshenko EG, Kuznetsov YA, Basovsky RN. Comparison of the energy histograms and conformations between different 231. Shouldice R, Heneghan C, Nolan P, Nolan PG, McNicholas W. lattice models of copolymers. Journal of Non-Crystalline Solids Modulating effect of respiration on atrioventricular conduction 2003;315:304-311. time assessed using PR interval variation. Medical & Biological Engineering & Computing 2002;40:609-617. 243. Ting, STL, Earley, B and Crowe, MA (2003). Effect of repeated ketoprofen administration during surgical castration of bulls 232. Smith TP, Suliman AM, Fahie-Wilson MN, McKenna TJ. Gross on cortisol, immunological function, performance and variability in the detection of prolactin in sera containing big behavior. J. Anim. Sci. 81:1253-1264. big prolactin (macroprolactin) by commercial immunoassays. Journal of Clinical Endocrinology and Metabolism 244. Ting, STL, Earley, B, Hughes JML and Crowe, MA (2003). 2002;87:5410-5415. Effect of ketoprofen, lidocaine local anesthesia, and combined xylazine and lidocaine caudal epidural anesthesia during 233. Solari V, Ennis S, Yoneda A, Wong L, Messineo A, Hollwarth castration of beef cattle on stress responses, immunity, ME, Green A, Puri P. Mutation analysis of the RET gene in total performance and behavior. J. Anim. Sci. 81: 1281-1293. intestinal aganglionosis by wave DNA fragment analysis system. Journal of Pediatric Surgery 2003;38:497-501. 245. Toomey D, Smyth G, Condron C, Kelly J, Byrne AM, Kay E, Conroy RM, Broe P, Bouchier-Hayes D. Infiltrating immune 234. Sortino S, Petralia S, Darcy R, Donohue R, Mazzaglia A. cells, but not tumour cells, express FasL in non-small cell lung Photochemical outcome modification of diflunisal by a novel cancer: No association with prognosis identified in 3-year cationic amphiphilic cyclodextrin. New Journal of Chemistry follow-up. International Journal of Cancer 2003;103:408-412. 2003;27:602-608. 246. Tosin M, Murphy PV. Synthesis of alpha-glucuronic acid and 235. Stallings RL, Howard J, Dunlop A, Mullarkey M, McDermott amide derivatives in the presence of a participating 2-acyl M, Breatnach F, O’Meara A. Are gains of chromosomal regions protecting group. Organic Letters 2002;4:3675-3678. 7q and 11p important abnormalities in neuroblastoma? Cancer Genetics and Cytogenetics 2003;140:133-137. 247. Tynan E, Jensen P, Kruger PE, Lees AC, Nieuwenhuyzen M. Coordination and hydrogen bonded networks featuring 4,4 ’- 236. Stenson C, Mitchell S, Lappin D, Brady HR, Godson C. Biphasic dicarboxy-2,2 ’-bipyridine (H(2)dcbp): structural regulation of leukocyte trafficking by lipoxins. Eicosanoids characterisation of H(2)dcbp, [Co(dcbp)(H2O)(4)]center dot and Other Bioactive Lipids in Cancer, Inflammation, and 4H(2)O, and {[Cu(dcbp)(H2O)(2)]center dot 2H(2)O}n. Dalton Radiation Injury, 5 2002;507:543-549. Transactions 2003;1223-1228.
248. Vallinoto ACR, Ishak MOG, Azevedo VN, Vicente ACP, Otsuki 237. Takahashi H, Sawa H, Hasegawa H, Sata T, Hall WW, Kurata K, Hall WW, Ishak R. Molecular epidemiology of human T- T. Binding and dissociation of human topoisomerase I with lymphotropic virus type II infection in Amerindian and urban hairpin- loop RNAs: implications for the regulation of HIV-1 populations of the Amazon region of Brazil. Human Biology replication. Biochemical and Biophysical Research 2002;74:633-644. Communications 2002;297:593-599.
249. van Keulen, G. and W.G. Meijer. 2003. Improved recovery of 238. Thin AG, Linnane SJ, McKone EF, Freaney R, FitzGerald MX, DNA from polyacrylamide gels after in situ DNA footprinting. Gallagher CG, McLoughlin P. Use of the gas exchange threshold Journal of Microbiological Methods 54;289-291 to noninvasively determine the lactate threshold in patients with cystic fibrosis. Chest 2002; 121(6):1761-70. 250. van Keulen, G., A.N.J.A. Ridder, L. Dijkhuizen and W.G. Meijer. 2003. Analysis of DNA binding and transcriptional activation 239. Thomas PM, Phillips JP, Delanty N, O´Connor WT. Elevated by the LysR-type transcriptional regulator CbbR of extracellular levels of glutamate, aspartate and gamma- Xanthobacter flavus. Journal of Bacteriology 185;1245-1252. aminobutyric acid within the intraoperative, spontaneously epileptiform human hippocampus. Epilepsy Research, 3290 251. Veale D, FitzGerald O. Psoriatic arthritis. Best Practice & 1-7 June 2003. Research in Clinical Rheumatology 2002;16:523-535.
FORTYTWO 240. Timoshenko EG, Kuznetsov YA, Connolly R. Conformations of 252. Veale DJ, FitzGerald O. Psoriatic arthritis - Pathogenesis and dendrimers in dilute solution. Journal of Chemical Physics epidemiology. Clinical and Experimental Rheumatology 2002;117:9050-9062. 2002;20:S27-S33. APPENDIX II (continued) ANNUAL REPORT 2003 CONWAY 253. Walsh JG, Gilheany DG. Easy access to medium rings by 264. Zintl A, Westbrook C, Skerrett HE, Gray JS, Mulcahy G. entropy/strain reduction, part 3. Competition between Chymotrypsin and neuraminidase treatment inhibits host cell
dihydroazepine and enamine formation in reaction of invasion by Babesia divergens (Phylum Apicomplexa). INSTITUTE tetrahalosubstituted dibromides with primary amines. Journal Parasitology 125: 45-50 Part 1 JUL 2002 of Heterocyclic Chemistry 2002;39:1273-1278.
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254. Wang XT, Au SWN, Lam VMS, Engel PC. Recombinant human BIOMOLECULAR glucose-6 phosphate dehydrogenase. European Journal of Biochemistry 269 (14): 3417-3424 JUL 2002.
255. Ward F, Rizos D, Boland MP, Lonergan P. Effect of reducing &
sperm concentration during IVF on the ability to distinguish BIOMEDICAL between bulls of high and low field fertility: work in progress. Theriogenology 2003;59:1575-1584.
RESEARCH 256. Wilson SJ, Keenan AK. Role of hemin in the modulation of H2O2-mediated endothelial cell injury. Vascular Pharmacology 2003;40:109-118.
257. Wong S, Fares MA, Zimmermann W, Butler G, Wolfe KH. Evidence from comparative genomics for a complete sexual cycle in the ‘asexual’ pathogenic yeast Candida glabrata. Genome Biology 2003;4:art-R10.
258. Wong S, Butler G, Wolfe KH. Gene order evolution and paleopolyploidy in hemiascomycete yeasts. Proc. Natl. Acad. Sci. USA 2003 (14): 9272-9277 JUL 9 2002
259. Wright C, Evans ACO, Evans NP, Duffy P, Fox J, Boland MP, Roche JF, Sweeney T. Effect of maternal exposure to the environmental estrogen, octylphenol, during fetal and/or postnatal life on onset of puberty, endocrine status, and ovarian follicular dynamics in ewe lambs. Biology of Reproduction 2002;67:1734-1740.
260. Yalloway GN, Lohr F, Wienk HL, Mayhew SG, Hrovat A, Knauf MA, Ruterjans H. Letter to the Editor: H-1, C-13 and N-15 assignment of the hydroquinone form of flavodoxin from Desulfovibrio valgaris (Hildenborough) and comparison of the chemical shift differences with respect to the oxidized state. Journal of Biomolecular NMR 2003;25:257-258
261. Yoneda A, Cascio S, Green A, Barton D, Puri P. Angiotensin II type 2 receptor gene is not responsible for familial vesicoureteral reflux. Journal of Urology 2002;168:1138-1141.
262. Young LS, Murphy G, Kelly SN, Smith TP, Cunningham SK, McKenna TJ. Differential production of adrenal steroids by purified cells of the human adrenal cortex is relative rather than absolute. European Journal of Endocrinology 2003;148:139-145.
263. Young LS, Murphy G, Kelly SN, Smith T, Cunningham SK, McKenna TJ. Differential production of adrenal steroids by purified cells of the human adrenal cortex is relative rather FORTYTHREE than absolute. Eur J Endocrinol 2003 148:139-145 CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH ANNUAL REPORT 2003 FORTYFOUR APPENDIX III Listing of Ph.D. thesis submissions during the period >from March 2002 – May 2003 ANNUAL REPORT 2003 CONWAY Examination of the Basis of Coenzyme Specificity ic Clostridial Central Control of the Crural Diaphragm Glutamate Dehydrogenase by Site-Directed Mutagenesis Human Anatomy & Physiology
Biochemistry INSTITUTE Epithelial-derived Mediators of Intestinal Inflammation and ADAM’s in Breast Cancer Defense
Biochemistry Pharmacology & Clinical Pharmacology OF
BIOMOLECULAR
The Microbial Diversity of Bottled Natural Mineral Water Low-density lipoprotein receptor related protein (LRP)and Industrial Microbiology Apolipoprotein E (ApoE)-mediated regulation of amyloid precursor protein (APP) expression and processing in the rat dentate gyrus
Protein Tyrosine Phosphatases in Human Malignant Melanoma during memory consolidation. &
Pathology Pharmacology & Clinical Pharmacology BIOMEDICAL
Differential Gene Expression in Mouse Mammary Epithelial Cells Contribution of MAP kinase Signalling to Mammary Epithelial Cell
Pharmacology Survival. RESEARCH Pharmacology & Clinical Pharmacology Regulation of Pro-Inflammatory Signalling Pathways by Exogenous and Endogenous Agents The Pathophysiological Role of Corticotropin-Releasing Hormone Pharmacology and NURRI in Human Inflammatory Arthritis. Pharmacology & Clinical Pharmacology Ets Transcription Factors in Human Breast Cancer Surgery The Use of Limited Proteolysis in the study of Thermostability in Xylanase A (X1n A) from Chaetomium thermophilum Investigations into the Involvement of Caveolae and Caveolin 1 in Biochemistry Prion Protein Biology Zoology The Chemistry of Z,Z-Muconate Esters Chemistry A 13 C-NMR Study of a Q-Chymotrypsin-glyoxal Inhibitor Complex. Biochemistry Studies in the Asymmetric Intramolecular Heck Reaction Chemistry A Biochemical Study of Five Rare Disease Causing Mutations of Medium chain Acyl CoA Dehydrogenase (MCAD): is there a Chromium-and Manganese-salen-Mediated Asymmetric Alkene Correlation Between Biochemical and Clinical Phenotype. Expoxidation Biochemistry Chemistry
Novel P-Chiral Compounds and Related Studies. Dynamic Measures of Medial Prefrontal and Cortio-tegmental Chemistry Glutatmate and GABA Transmission in Intact Conscious Brain Human Anatomy & Physiology The Effects of Interleukin-18 and Stress-Activated Protein Kinase Inhibitors on Synaptic Transmission and Plasticity in the Rat The Expression and Role of the Inhibitors of Apoptosis Proteins in Dentate Gyrus in Vitro. Prostate Cancer Human Anatomy & Physiology Medicine & Therapeutics
The Effect of B-Amyloid (AB) Peptides on Synaptic Transmission The Fibulins: Physiological and Pathophysiological Implications and Synaptic Plasticity in the Hippocampal CA1 Area of the Rat Pharmacology & Clinical Pharmacology In Vivo. Human Anatomy & Physiology Nuclear Regulators and Cell Signalling in the Mammary Gland Pharmacology & Clinical Pharmacology The Effects of IL-1B and Kinase Signalling on Synaptic Plasticity in the rat dentate gyrus in vitro. Human Anatomy & Physiology
Dynamic Measures of Striopallidal GABA Transmission. A Microdialysis Study in Intact Conscious Brain. Human Anatomy & Physiology FORTYFIVE APPENDIX IV Listing of lectures in Discipline Integration & >Technology Transfer Series 2002/2003 NULRPR 2003 REPORT ANNUAL CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH June 19th 2003 Dr. Gerard Cagney, Royal College of Surgeons in Ireland, “Proteomic Dr. Stephen Daly, “Applications of Surface Plasmon Resonance Analysis of a Eukaryotic Model: Strategies and Applications”. (SPR) in biological systems”. School of Biotechnology and National Centre for Research, Dublin City University. Dr. William Gallagher, University College Dublin, “Protein expression profiling in cancer via protein chip technology: case Dr. Geraldine Butler, “Virulence characteristics in Candida species”. studies”. Dept of Biochemistry, UCD. Professor Robert Kelsh, University of Bath “Zebrafish as a model Dr. Nigel Pitt,“Synthesis of novel glucuronic acid conjugates and system - the genetics and cell biology of neural crest development”. the evaluation of their effects on heparin/heparan sulfate binding to FGF and fibronectin”. Dept. of Chemistry, UCD. Dr. Carmel Hensey, University College Dublin “Gremlin function in Xenopus pronephric development”. Dr. Breandan Kenny, Welcome Trust, Senior Fellow for Basic Biomedical Sciences, University of Bristol. “Synergistic and Dr. Kevin Mitchell, Trinity College Dublin “Elucidating the genetic antagonistic action of enteropathogenic E. coli (EPEC) effector basis of brain wiring using a functional genomic approach in mouse”. molecules in the modulation of host cellular processes”. Professor Divyen Patel, St. Jude Children’s Research Hospital, April 17th 2003 Memphis, TN USA. “Gene chips/microarrays overview: clinical Dr Declan Gilheaney, “Celtic Catalysts”, Department of Chemistry, applications and future prospects”. UCD. Dr. David McHugh, University College Dublin “Genomics and complex Prof Peter Dervan, “Pathology Practice - not Perfect”, Department traits in domestic cattle”. of Pathology, Mater Misericordiae University Hospital. Dr. Stephen Pennington, University of Liverpool “The Application Ms Orla Bergin, “Molecular events in melanoma progression of Proteomics to Biomedical Sciences: Existing and Emerging transcriptome patterns in malignant melanoma: Correlation with Strategies”. Phenotypic, genomic and epigenetic alterations”, Departments of Pathology and Pharmacology. Dr. Cliona O’Farrelly, St. Vincent’s Hospital and UCD, “Hunting Genomes for New Anti-Microbial Peptides: a Chicken & Egg Story.” Professor Frans van Roy,“Role of the cadherin-catenin complex and related molecules in tumour progression”, Department for Molecular Professor Randy Mrsny, University of Cardiff “Drug delivery options Biomedical Research, VIB-Ghent University, Ghent, Belgium. and opportunities for protein and peptide-based therapeutics”.
March 20th 2003 Professor Michael P. Ryan, University College Dublin “Strategies Dr Mark Rogers, “Chance in the successful commercialisation of for development of the Centre for Integrative Biology ”. technology; personal experiences in licensing Prion test technology” Department of Zoology. January 16th 2003 Dr Conor Heneghan, Dept. of Electronic and Electrical Engineering, Dr Isabel Rozas, “New aliphatic ligands for I2-imidazoline binding UCD. “Digital signal processing and the electrocardiogram: new sites” CSCB, Department of Chemistry, Trinity College Dublin. insights into cardiac function”.
Dr Keith Murphy, “Brain plasticity as a therapeutic target” Professor Paul McLoughlin, Dept. of Human Anatomy and Department of Pharmacology. Physiology, UCD. “Disease-induced remodelling in organs and organisms: Common problems (and solutions) in the analysis of Dr. Arne Schousboe, “Characterisation of GABA metabolism and tissue structure”. transport in the GABAergic synapse: neuron-glial crosstalk” Department of Pharmacology, NeuroScience PharmaBiotec Dr Ursula Fearon, Dept. of Rheumatology. “The role of angiopoietins Research Center, The Royal Danish School of Pharmacy, in inflammatory arthritis”. Copenhagen. Professor Phillip Hawkins, Babraham Institute, Cambridge, UK. February 20th 2003 “Signalling via PI3 kinases”. Symposium Centre for Integrative Biology Professor Ken Wolfe, Trinity College Dublin “Comparative genomics December 17th 2002 and genome evolution”. Symposium Centre for Synthesis and Chemical Biology Professor Thomas O’Halloran, Northwestern University “Chemistry
FORTYSIX Dr. Torres Sweeney, University College Dublin “Uptake of prion of the Cellular Cytoplasm: Receptors for Monitoring and Controlling proteins by sheep genotyped to be scrapie-sensitive or insensitive: Metal Ion Activity”. implications for oral transmission of prion diseases”. APPENDIX IV (continued) ANNUAL REPORT 2003 CONWAY Professor Dorit Hanein, The Burnham Institute “Deciphering the September 12th 2002 structure of biological machines at the leading edge of motile cell”. Conway Research Festival
Dr. Seamas Donnelly, ERC St. Vincent’s University Hospital and INSTITUTE Professor Dudley Williams, Cambridge University “Volume Conway Institute, UCD “Macrophage Migration Inhibitory Factor Reductions in Receptors and Enzymes as a Source of Ligand Binding (MIF) in inflammatory disease”.
Energy and Catalytic Efficiency”. OF
Professor Brian Harvey, RCSI Research Professor, Chair of BIOMOLECULAR Professor Bernhard Lippert, Universität Dortmund “Where Molecular Medicine, Royal College of Surgeons in Ireland “Rapid Bioinorganic Chemistry meets Molecular Architecture:Modelling Responses to Steroid Hormones: From Molecule To Malady” Metal-Nucleic Acids Interactions”.
Dr. Paul Murphy, Dept. of Chemistry and Conway Institute, UCD &
Professor Richard J. K. Taylor, University of York “Synthetic “Combining Design and Diversity to Identify Novel Inhibitors of BIOMEDICAL Approaches to Phthoxazolin A and Oxazolomycin A”. Enzymes and Carbohydrate Binding Proteins”.
Professor Amos B. Smith, University of Pennsylvania Dr Barry Buckland, Bioprocess Research and Development, Merck RESEARCH “(+)-Discodermolide: A Potentially Important Antitumor Agent”. Research Laboratories, USA “The Future of Bioprocessing – an International Perspective”. November 21st 2002 Dr Raphael Darcy, Dept. of Chemistry and Conway Institute, UCD Dr. Mark Rogers, Dept. of Zoology and Conway Institute, UCD “Cyclodextrins and Cytrea - a biotech present for a campus company “Models of prion disease in vitro and in vivo”. future”. Professor Roger Patient, Institute of Genetics, University of Ms. Elaine Quinn, Conway Institute “Research Information System Nottingham, UK “The origins and programming of blood stem cells”. in UCD”. June 20th 2002 Dr. Pat Caffrey, Dept. of Industrial Microbiology, UCD “Engineered Mr. Jimmy Maher, PriceWaterhouseCooper “Fund Raising, biosynthesis of amphotericin analogues”. Corporate Finance Terms and What Funders are looking for in the Business Proposition”. Dr. Sharon Cookson, Dept of Pediatrics, Our Lady’s Hospital for Sick Children, Crumlin “T-Cell Ontogeny in Early Life”. Professor Andrew Green, National Centre for Medical Genetics, Our Lady’s Hospital for Sick Children. “Hereditary Breast Cancer Dr. Jack Elias, Dept of Internal Medicine, Yale University School of in Ireland”. Medicine Plenary Lecture: “Transgenic Modeling of IL-13 in the Lung”. Dr. Carmel Hensey, Department of Pharmacology, University College Dublin. “Developmentally regulated cell death programmes October 17th 2002 in Xenopus embryos”. Dr Benjamin Reed, ProteinChip specialist, Ciphergen “ProteinChip® Technology- Revolutionising Proteomic Dr. Simon Campbell FRS, formerly Senior Vice-President for Approaches”. Worldwide Discovery and Medicinals R&D Europe, Pfizer. “Science, Art and Drug Discovery, a Personal Perspective”. Dr. Donal O’Shea, Dept. of Chemistry, and Conway Institute, UCD “Development of new light induced cell death agents”.
Dr. Janice Murtagh, Dept. of Pharmacology and Conway Institute,UCD “A novel glucocorticoid-triggered signalling pathway induces functional differentiation of 3D-mammary epithelial cell structures”.
Prof. Seamus Martin. Dept. of Genetics, The Smurfit Institute, Trinity College Plenary Lecture:“Manipulating the Apoptotic Pathway – where and how”. FORTYSEVEN NOTES
CONWAY INSTITUTE OF BIOMOLECULAR & BIOMEDICAL RESEARCH ANNUAL REPORT 2003 FORTYEIGHT
CONTACT DETAILS FURTHER DETAILS
Conway Institute of Biomolecular www.ucd.ie/conway and Biomedical Research University College Dublin, Belfield, Dublin 4, Ireland.
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