Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras PI name & contact details: Deniz Tasdemir, Established Professor of Marine Biodiscovery School of Chemistry, NUI Galway Phone: +353-(0)91-492450, Fax: +353-(0)91-495576 e-mail: deniz.tasdemir@nuigalway.ie Co-PI name & contact details Dr. Thomas Ritter, Senior Lecturer in Medicine, NUI Galway Phone: +353-(0)91-495329, Fax: +353-(0)91-495547 e-mail: thomas.ritter@nuigalway.ie School of Chemistry School: Has project been agreed with head (or nominee) of proposed registration school? Yes Research Centre / group affiliation: Research group / centre website: PI website / link to CV: Marine Biodiscovery Research Group http://www.nuigalway.ie/chemistry/level2/staff/DenizTasdemir /dtgrouppage.html http://www.nuigalway.ie/chemistry/level2/staff/DenizTasdemir /dtresearch.html Brief summary of PI research / research group / centre activity (2 or 3 lines max): The research emphasis of the PI is the discovery of new drug lead molecules from marine organisms that can be developed pharmaceutically for treating human diseases and to find applications in biomedical area. It is a highly multisdisciplinary research subject, including natural product chemistry, pharmacology, molecular biology, immunology, clinical research. Title & brief description of PhD project (suitable for publication on web): Discovery of novel molecules from marine sponges for application in inflammatory diseases of the eye Oceans cover 70% of the earth surface. The immeasurable chemical and biological diversity of the marine environment makes oceans an extraordinary resource for the discovery of new drugs. Indeed, several marine natural products have been approved for human use and many are under clinical evaluations. This project will evaluate the potential of anti-inflammatory and immunomodulatory secondary metabolites produced by marine organisms in ocular inflammation and keratoplasty (transplantation of corneal material to replace scar tissue which interferes with vision). Several factors such as infection or trauma can cause corneal inflammation. This can affect corneal clarity and cause scar formation, which eventually necessitates keratoplasty. Moreover, any form of ocular surface inflammation also poses an increased risk of transplant rejection thus requiring immunosuppressive therapy. Corticosteroids are widely used for controlling immune reaction following keratoplasty and to reduce subsequent inflammatory corneal reaction. However, even the topical application of steroids is associated with serious risks such as ocular hypertension and cataract development. Hence, there is a need to develop alternatives to corticosteroids. Marine organisms, particularly sponges produce potent anti-inflammatory molecules, some of which also show strong immunomodulatory effects. In preliminary studies several crude extracts obtained from marine organisms were found to show remarkable anti-inflammatory and immunosuppressive activity. In this project the promising extracts with high immunosuppressive and/or antiinflammatory activity will be purified by chromatographic methods and tested in in vitro assays Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras such as inhibition of TNF by LPS stimulated monocytes and inhibition of proliferation of activated T cells developed by the co-PI as a guide. Chemical characterization of the active constituents of the extracts will be achieved by high resolution spectroscopy methods (NMR, MS, LC-MS). After extensive in vitro testing, active compounds will be tested in vivo in inflammatory diseases of the eye (dry eye, keratoplasty). Moreover, co-application of new compounds with mesenchymal stem cells will be investigated to further improve immunosuppressive therapy. This project is expected to yield marine molecules superior to corticosteroids with higher potency and safety. Such compounds will have realistic potential to be developed commercially. Unique selling points of PhD project in NUI Galway: The cross-disciplinary nature of this project will provide the student with a range of techniques at the cutting edge of natural product chemistry, cell biology and immunology, and prepare the student for a career in drug discovery and inflammation research in an academic or industrial settings. On the other hand, Chemistry PhD programme will provide the student with a diverse range of additional subject-specific and non-specific didactic elements as part of the structured PhD programme. The student will have access to the following: A state of the art infrastructure in natural products chemistry at the PI’s research group (automated fractionation techniques, HPLC, UPLC-MS/MS) and in School of Chemistry (400, 500, 600 NMR with cryoprobe, LC-MS, X-ray crystallography) A wide range of expertise/training including the areas of drug discovery, natural products chemistry, stem cell biology, immunology, molecular biology, translational research A wide network of collaborating researchers in Ireland and worldwide Collaboration with REMEDI (Regenerative Medicine) group in NUIG which will provide access to core technical facilities e.g. flow cytometry, microscopy, cell culture, histology, molecular biology Name & contact details for project queries, if different from PI named above: Please indicate the graduates of which disciplines that should apply: Pharmacy, Chemistry, Biomedical Sciences, Biology, Cell biology, Pharmacology Ciência sem Fronteiras / Science Without Borders Priority Area: Please indicate the specific programme priority area under which the proposed PhD project fits- choose only one (tick box): Engineering and other technological areas Pure and Natural Sciences (e.g. mathematics, physics, chemistry) Health and Biomedical Sciences Information and Communication Technologies (ICTs) Aerospace Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras Pharmaceuticals Oil, Gas and Coal Renewable Energy Minerals Biotechnology Nanotechnology and New Materials Technology of prevention and remediation of natural disasters Biodiversity and Bioprospection Marine Sciences Creative Industry New technologies in constructive engineering X Please indicate which of the following applies to this project (referring to Science Without Borders arrangements): Suitable only as a Full PhD (Y/N): _ ___Y_ Available to candidates seeking a Sandwich PhD arrangement (Y/N): ___N__ Suitable for either/Don’t know: _____