Objective Mutations in BRCA1 and BRCA2 genes confer high lifetime risks of developing breast and other cancers. Moreover, several studies suggest that tumours arising in mutation carriers have generally lost the wild-type allele and do not express functional BRCA1 or BRCA2 proteins. Both BRCA proteins are important for repair of double strand DNA breaks by homologous recombination. The subject of this project would allow us to clarify if cells harbouring defects in DNA damage repair (such as BRCA1 deficient cells) are more sensitive to the induced loss of other DNA repair mechanisms (either by RNAi or small molecule inhibitors). For that purpose I will perform High-throughput RNA interference screenings to find synthetic lethality partners for BRCA1 and BRCA2, using a library of siRNAs targeting 779 proteins that encompass all the known and predicted kinases. I will also translate some previous yeast synthetic lethality studies, to human breast cancer cell lines, performing for that a”mini-RNAi screen”. Ultimately, this project presented here may lead to the identification of novel anticancer strategies targeting DNA repair defects in tumors, which could be applicable in several sporadic cancers. Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologybreast cancernatural sciencesbiological sciencesgeneticsmutationnatural sciencesbiological sciencesgeneticsRNA Keywords BRCA Breast cancer DNA repair Kinases RNAi anticancer therapeutics Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) PEOPLE-2007-2-1.IEF - Marie Curie Action: "Intra-European Fellowships for Career Development" Call for proposal FP7-PEOPLE-2007-2-1-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator INSTITUTE OF CANCER RESEARCH: THE ROYAL CANCER HOSPITAL LBG EU contribution € 169 390,93 Address OLD BROMPTON ROAD 123 SW7 3RP London United Kingdom See on map Region London Inner London — West Kensington & Chelsea and Hammersmith & Fulham Activity type Higher or Secondary Education Establishments Administrative Contact Binoo Rastogi (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
