Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras PhD Project Template Use one form per project Please complete & submit to international@nuigalway.ie as soon as possible, and by 27/11/2012 In your email, begin the subject line with [SWB] (be sure to use square brackets) to ensure that your email is filed correctly. Emails will be automatically filed PI name & contact details: School: Dr. Michael P. Carty Michael.carty@nuigalway.ie School of Natural Sciences, Biochemistry, NUI Galway Has project been agreed with head (or nominee) of proposed registration school? yes Research Centre / group affiliation: Dr. Carty: Centre for Chromosome Biology, NUI Galway, in collaboration with Prof. Frank Barry, Regenerative Medicine Institute, NUI Galway DNA Damage Response laboratory, Centre for Chromosome Biology http://www.chromosome.ie/researchers/carty/ Prof. Barry: http://www.remedi.ie/research Research group / centre website: PI website / link to CV http://www.nuigalway.ie/biochemistry/staff/carty/index.html Brief summary of PI research / research group / centre activity (2 or 3 lines max): The main aim of the DNA Damage Response group led by Dr. Carty is to elucidate the molecular basis of the response of human primary cells and cancer cells to DNA damaging agents, including platinum-based cancer therapeutic drugs and ionizing radiation. Title & brief description of PhD project (suitable for publication on web): DNA damage responses in human mesenchymal stem cells (hMSCs). DNA damage to the stem cell population can have serious consequences for the organism. Human mesenchymal stem cells (hMSCs) are a key population of stem cells in the bone marrow. hMSCs are progenitors of osteoblasts, adipocytes and chondrocytes, and also play an important role in maintenance of haematopoietic stem cells (HSCs). There is evidence that exposure of hMSCs to DNA damage from radiotherapy and chemotherapy during cancer treatment can affect tissue homeostasis, as well as modulating tumour cell behaviour. In collaboration with Prof. Frank Barry in the Regenerative Medicine Institute, NUI Galway, we have developed systems to characterise the DNA damage response in hMSCs from normal donors and from a patient with leukaemia to DNA damaging agents used in cancer treatment, including radiation, cisplatin and doxorubicin (1-3). hMSCs respond to DNA damage by induction of strong cell cycle arrest rather than undergoing apoptosis (2,3). In the present project, the molecular basis of this response will be investigated in cultured hMSCs, to determine the key pathways that determine the outcome of exposure. The effects of DNA damage on DNA repair, cell signalling, and induction of genomic alterations in hMSCs that survive Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras DNA damage will be investigated, using cellular, molecular, genomics and proteomics-based approaches. The research will provide novel insights into the factors that determine the outcome of exposure to DNA damage in hMSCs, with implications for cancer treatment. This interdisciplinary project will provide training in stem cell biology, and in biochemical and molecular analysis of key DNA damage response pathways in a critical stem cell population in the human bone marrow. See related publications: 1. Cruet-Hennequart et al. Current Cancer Drug Targets 10, 411-421 (2010) Review 2. Prendergast et al. Cell Cycle 10, 3768-3777 (2011) 3. Cruet-Hennequart et al. Int. J. Hematol. 96, 649-656 (2012) Unique selling points of PhD project in NUI Galway: NUI Galway projects should emphasise features that are not typically available in Brazil – specific equipment, multi-disciplinarity, aspects of structured programme, links with industry, placements, links with other research groups etc. State-of-the-art facilities are available in Biochemistry, the Centre for Chromosome Biology, and REMEDI, including cell culture facilities, flow cytometry and cell sorting, fluorescence microscopy with live cell imaging, and systems for gene and protein analysis. High-level training in the use of all equipment, procedures and data analysis will be provided. Students will be part of the structured PhD programme in Biochemistry in the School of Natural Sciences, focused on Biochemistry. As part of this programme, in addition to the research thesis, students take a series of focused modules aimed at developing core professional skills and knowledge in areas relevant to future career development. The DNA Damage Response group has a strong record of graduating PhD students, and in research publication. This is a highly Interdisciplinary project involving collaboration with the Regenerative Medicine Institute (REMEDI) a leading institute focused on the biology of adult stem cells and the development of therapeutic applications of these cells. The DNA Damage Response laboratory is part of the Centre for Chromosome Biology, a network of 11 research groups with high-level expertise in all aspects of chromosome biology. Students will have opportunities to present their results in the weekly seminar series of the Centre for Chromosome Biology where feedback from faculty and researchers directly working in the field provides an invaluable learning experience. Biochemistry and the Centre for Chromosome Biology host a strong seminar programme, where invited national and international research leaders present the latest results. 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: Biochemistry, Biotechnology, Molecular/Cellular Biology 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 x Information and Communication Technologies (ICTs), Computing Aerospace Pharmaceuticals 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): _ N (collaboration could also be considered) Available to candidates seeking a Sandwich PhD arrangement (Y/N): __Y___ Suitable for either: ___Y__