Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras PI name & contact details: Prof. 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. Michael Carty, Senior Lecturer Biochemistry, and Centre for Chromosome Biology School of Natural Sciences, NUI Galway Tel: 353-(0)91-493695, Fax: 353-(0)91-495504 e-mail: michael.carty@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: Marine Biodiscovery Research Group http://www.nuigalway.ie/chemistry/level2/staff/DenizTasdemir/dt grouppage.html PI website / link to CV: http://www.nuigalway.ie/chemistry/level2/staff/DenizTasdemir/dtr esearch.html Brief summary of PI research / research group / centre activity (2 or 3 lines max): The main research focus is directed at marine bioprospecting, with the ultimate aim of discovering new drugs/drug lead molecules from marine organisms. These compounds can be developed pharmaceutically to prevent or treat human diseases, such as cancer. It is a highly multisdisciplinary research, including natural product chemistry, cancer biology, biochemistry, clinical research. Title & brief description of PhD project (suitable for publication on web): Discovery of novel sunscreen natural products from marine organisms Rising levels of harmful UV rays are reaching the earth’s surface due to the thinning of the ozone layer worldwide. It is now widely accepted that continuous exposure to UV irradiation (both UV-A and UV-B) leads to the skin cancer and other photo-aging complications. UV irradiation induces oxidative stress responses via the generation of reactive oxygen species (ROS) that interact with cellular biomolecules e.g. DNA, proteins and fatty acids causing oxidative damage. Hence photoprotection, through topical use of sunscreen agents has become a primary preventive measure. However this it may not be sufficient for some skin cancers, such as non-melanoma skin cancers (NMSC), so additional approaches and strategies are needed. Marine organisms, particularly those found in shallow waters are under continuous solar irradiation. In order to minimize or counteract the photo-damage, they produce various classes of photoprotective and UV-absorbing substances, some of which are under evaluation for their topical sunscreen effects in humans. This project will try to discover and develop novel, safe, natural marine molecules with broad-spectrum UV protective potential. It will involve testing of crude extracts obtained from various seaweeds, as well as marine macro- and microorganisms. The extracts will be tested against human cell lines, including primary human keratinocytes and melanocytes, and Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras established non-melanoma and melanoma skin cancer cell lines. The ability of extracts to protect against UVB and UVA-induced cytotoxicity will be analysed using cell viability assays and clonogenic survival assays. The induction of UV-induced DNA damage will be analysed by determining the effect of the extracts on the induction of UV-induced photoproducts and oxidative lesions in genomic DNA, using specific antibodies to detect lesions in cellular DNA. Effects of extracts of UV-induced DNA damage signalling pathways will be determined using immunofluorescence and western blotting. The ability of selected extracts to induce cytotoxicity in skin cancer cell lines will be analysed using cell viability assays. The promising extracts with UV-protective activity will be purified by chromatographic methods and tested in vitro for effects on cell viability and UV-damage induction as guide. Chemical characterization of the active constituents of the extracts will be performed by high resolution spectroscopic methods (NMR, MS, LC-MS). The mechanism of action of promising photoprotective or chemotherapeutic compounds will be further investigated by analysis of changes in genes and proteins involved in key cell signalling pathways. This project is expected to yield marine natural products with strong cosmeceutical and pharmaceutical value. Such compounds may have realistic potential to be developed commercially for topical and/or internal use for solar protection, skin cancer chemopreventive or chemotherapeutic activities. Unique selling points of PhD project in NUI Galway: This project is very multidisciplinary that will provide the student with a range of techniques at the cutting edge of natural product chemistry, biochemistry, cell biology and cancer biology, and prepare the student for a career in drug discovery, natural product and cancer research in an academic or industrial setting. 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, biochemistry, molecular and cell biology, cancer biology, translational research Collaboration with Dr. Michael Carty (co-PI) in NUIG will provide access to core technical facilities and techniques such as mammalian cell culture facilities, flow cytometry, fluorescence microscopy, and systems for analysis of protein, DNA and gene expression (western blotting, immunofluorescence, qPCR). A wide network of collaborating researchers (academic and industrial) in Ireland and worldwide Name & contact details for project queries, if different from PI named above: Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras 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)/Physical Sciences (Mathematics, Physics, Chemistry, Biology and Geosciences) Health and Biomedical Sciences / Clinical, Pré-clinical and Health Sciences Information and Communication Technologies (ICTs), Computing Aerospace Pharmaceuticals X Sustainable Agricultural Production Oil, Gas and Coal Renewable Energy Minerals, Minerals Technology Biotechnology Nanotechnology and New Materials Technologies for Prevention and Mitigation of Natural Disasters Bioprospecting and Biodiversity Marine Sciences Creative Industry New technologies in constructive engineering 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: _____