Objective The prime objective for every life form is to deliver its genetic material, intact, to the next generation. Each human cell receives tens-of-thousands of DNA lesions per day. These lesions can block genome replication and transcription, and if not repaired or repaired incorrectly, they lead to mutations or wider genome aberrations that threaten cell viability. To counter such threats, life has evolved the DNA-damage response (DDR), to detect DNA damage, signal its presence and mediate its repair. DDR events impact on many cellular processes and, crucially, prevent diverse human diseases that include cancer, neurodegenerative diseases, immune-deficiencies and premature ageing. While much progress has been made in identifying DDR proteins, much remains to be learned about the molecular and cellular functions that they control. Furthermore, the frequent reporting of new DDR proteins in the literature suggests that many others await identification. The main goals for the proposed research are to: identify important new DDR-proteins and DDR-modulators, particularly those responding to DNA double-strand breaks (DSBs); provide mechanistic insights into how these proteins function; and determine how DDR events are affected by chromatin structure, by molecular chaperones and components of the Ubiquitin and Sumo systems. To achieve these ends, we will use molecular biology, biochemical, cell-biology and molecular genetics approaches, including synthetic-lethal and phenotypic-suppression screening methods in human cells and in the nematode worm. This work will not only be of academic importance, but will also indicate how DDR dysfunction can cause human disease and how such diseases might be better diagnosed and treated. Fields of science natural sciencesbiological sciencesmolecular biologymolecular geneticsnatural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsgenomes Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS1 - ERC Advanced Grant - Molecular and Structural Biology and Biochemistry Call for proposal ERC-2010-AdG_20100317 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE EU contribution € 2 482 492,00 Address TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge United Kingdom See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Principal investigator Stephen Philip Jackson (Prof.) Administrative Contact Renata Schaeffer (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE United Kingdom EU contribution € 2 482 492,00 Address TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Principal investigator Stephen Philip Jackson (Prof.) Administrative Contact Renata Schaeffer (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
