Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras PhD Project Template PI name & contact details: School: Has project been agreed with head (or nominee) of proposed registration school? Research Centre / group affiliation: Research group / centre website: Prof Noel Francis LOWNDES Biochemistry/School of Natural Sciences Yes Centre for Chromosome Biology / Genome Stability Laboratory http://www.chromosome.ie PI website / link to CV: http://www.chromosome.ie/researchers/lowndes Brief summary of PI research / research group / centre activity: If you are already involved in relevant scholarly activities relating to Brazil, please mention them here. Professor Lowndes’ research career spans two decades in leading research laboratories in the USA, UK and Ireland. He was appointed to the Chair of Biochemistry at the National University of Ireland Galway in 2001 where he leads the Genome Stability Laboratory. His group investigates mechanisms of sensing and responding to DNA damage using yeast, DT40 and human cells. His leadership of the Centre of Chromosome Biology (www.chromosome.ie/) has been pivotal in positioning NUIG at the forefront of Irish cancer biology. In 2003, Professor Lowndes was elected to the membership of the European Molecular Biology Organisation, one of 5 EMBO members in Ireland. Title & brief description of PhD project (suitable for publication on web): The role of RNA binding protein in the cellular responses to DNA damage: DNA damage must be recognized and appropriate cellular responses triggered to protect genomic integrity and prevent cancer. Surprisingly, recent work implicates a role for RNA binding proteins in the DNA damage response (DDR). Consistent with this possibility our recent proteomic screening has identified a number of RNA binding proteins with novel roles in the DDR. In this project the regulation, function and mechanism of candidate RNA binding protein in the DNA damage response will be characterized in detail and the hypothesis that aberrant regulation of these protein may be implicated in carcinogenesis will be investigated. Hypothesis and specific aims: Our general hypothesis is that specific RNA binding proteins are required for the DDR. Aims : 1) Establish the role of our candidate RNA binding proteins in the cellular responses DSBs 2) Determine whether any of these protein plays roles in the aetiology of cancer. Experimental Plan: 1) Use ‘knock-down’ (siRNA and shRNA) and ‘knock-out’ (gene targeting) approaches to abrogate gene function and study cellular responses to DNA damage using well established assays 2) Screen for perturbed expression in cancer cell lines and cancer samples The high novelty of our preliminary observations has begun to elucidate new biological mechanisms required for a successful DNA damage response. Detailed characterisation of these mechanisms will result in publications in leading internationally peer review publications. Importantly, the new factors identified will be assesed for their future potential as new cancer therapeutic targets. Unique selling points of PhD project in NUI Galway: 1) The PI is an internationally leading researcher in genome stability studies 2) Excellent multidisciplinary laboratory facilities (note, in July 2013 the host laboratory will relocate to the new BioScience Building at NUIG , see http://www.guf.ie/index.php/priority- Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras projects/project_detail/biosciences-research-building1/) 3) Strong collaborative links with international leaders in the field within Europe and the USA. 4) Excellent track record in the field 5) Strong funding record, including national (SFI/HRB), international (EU) and philantrophic (O’Sullivan Biomedical Trust) agencies 6) Strong strategic focus on Biomedical Science 7) Strong technical background in: a. Genetics (use of gene targeting for either ablating gene function or acquisition of new functions) b. Biochemistry (protein functions & interaction, quantitiative proteomics) c. Cell Biology (fixed and live cell microscopy) d. Advanced specialist techniques (DNA combing, isolation of proteins on nascent DNA, elutriation, stable isotope labelling with amino acids in cell culture or SILAC) 8) Nearby Brazilian community (see: http://euscreen.eu/play.jsp?id=EUS_346071ABF1C64166BF02025C40B29ED8) Please indicate the graduates of which disciplines that should apply: Biochemistry, Biotechnology, Biomedical Science, Cell Biology, Genetics, Pharmacology, physiology, or any other comparable discipline of Molecular Biology Ciência sem Fronteiras / Science Without Borders Priority Area: Please indicate the specific programme priority area under which the proposed PhD project fits- only one : 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 Sustainable Agricultural Production Oil, Gas and Coal Renewable Energy Minerals, Minerals Technology Biotechnology X 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): Suitable only as a Full PhD (Y/N): _Yes_ Available to candidates seeking a Sandwich PhD arrangement (Y/N): _No_