Version 2 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. Róisín Dwyer, Lecturer in Translational Science Discipline of Surgery, School of Medicine, NUI Galway Phone +353-(0)91-524390, Fax: +353-(0)91-494509 Email: Roisin.dwyer@nuigalway.ie School: School of Chemistry 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 /dtgrouppage.html PI website / link to CV: 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 focus of the PI is mainly directed at discovery of new drugs and drug lead molecules from marine organisms that can be developed pharmaceutically to treat human diseases, such as cancer. It is a highly multisdisciplinary research subject, including natural product chemistry, pharmacology, cellular and molecular cancer biology, clinical research. Title & brief description of PhD project (suitable for publication on web): Targeting cancer stem cells with marine natural products, a new approach in cancer drug discovery and development Cancer stem cells (CSCs) are a distinct group of self-renewing cells that are able to proliferate and differentiate into multiple cell types. It is now widely accepted that many type of cancers are driven by a small group of cancer stem cells. CSCs are believed to be associated with failure in chemo- or radiotherapy that lead to relapse or metastasis of the disease, as the current anticancer agents are ineffective against CSCs. By selectively targeting the CSCs, it would be possible to treat many aggressive and/or metastatic tumors and improve patient survival. Therefore CSCs offer an emerging and thriving new field of research. Cancer drug discovery has been the main stream of marine natural products research, already yielding several compounds (Yondelis®, Halaven®) approved for the treatment of human cancers. However, CSCs has remained an untouched area in marine natural product discovery. The aim of this project hence will be identifying novel compounds from marine organisms that target cancer stem cells in breast tumours at the co-PI’s lab in NUIG. It will involve testing of crude marine extracts Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras against breast cancer cell lines and primary cultures of breast tissue specimens. The effect of extracts on cell viability, proliferation, migration and invasion will be determined, with a particular focus on cells expressing markers associated with CSCs (CD44+CD24lo, ALDH1+). The promising extracts with high cytostatic/cytotoxic activity will be purified by various chromatographic methods by using in vitro assays as a guide. Flow cytometry will be used to determine the cell population upon which the marine extract is most effective. Chemical characterization of the active constituents of the extracts will be performed by high resolution spectroscopy methods (NMR, MS, LC-MS). The mode of action of the active constituents will then be determined, e.g. if cell death is induced, it will be determined whether this was mediated through apoptosis and whether the caspase cascade was activated. Changes in cancer-associated gene and protein expression profiles can also be monitored in response to the extract of interest. This project is expected to yield marine natural products with a novel mode of anticancer activity. Such compounds may have realistic potential to developed commercially. Unique selling points of PhD project in NUI Galway: This multidisciplinary project will provide the student with a range of techniques at the cutting edge of natural product chemistry, molecular/cell biology and various aspects of cancer research. This will prepare the student for a career in anticancer drug discovery in an academic or industrial settings. Moreover, 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, cancer cell and molecular biology, translational research Collaboration with Discipline of Surgery and National Breast Cancer Research Institute research groups in NUIG will provide access to core technical facilities e.g. cell culture, flow cytometry, immunohistochemical analysis, CSC identification, RNA extraction, RQ-PCR 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: Please indicate the graduates of which disciplines that should apply: Pharmacy, Chemistry, Biomedical Sciences, Biology, Cell biology, Pharmacology Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras 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: _____