Objective
DNA is a highly reactive molecule that is subject to deliberate, spontaneous and environmental damage. One of the most catastrophic lesions in DNA is the double-strand break (DSB), which if left unrepaired can result in cell death, infertility, genome instability and cancer. Homologous recombination (HR) is a largely error-free mechanism of DSB repair that utilizes an intact sister or homologous chromosome as a repair template. Despite considerable progress in understanding the mechanisms of HR, very little is known about how this process is regulated. My lab has made a number of seminal discoveries that have improved our understanding of how HR is regulated in mitotic and meiotic cells. In this ERC proposal, we plan to elucidate the mechanisms that control HR events in mitotic cells and regulate HR pathway choice during meiotic recombination. We will place particular emphasis on defining the roles of RTEL1 and HELQ1 in regulating HR in mitotic and meiotic cells and will determine how dysfunction of these genes contributes to tumorigenesis. Biochemistry and proteomic approaches will be employed to determine how the Fanconi anemia (FA) pathway counteracts error-prone repair by non-homologous end joining (NHEJ), thus favouring HR repair in S-phase. The use of NHEJ inhibitors as a potential treatment of FA will be tested in existing mouse models of FA. Finally, genetic screens and proteomic analysis of HR regulators will be performed in C. elegans to elucidate the mechanisms that regulate the choice between crossover and non-crossover pathways during meiotic HR. Thus, in the work proposed here, my lab will make use of multiple experimental approaches to elucidate the mechanisms for control of HR and the consequences of dysregulated HR on human disease.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine oncology
- medical and health sciences clinical medicine hematology
- natural sciences biological sciences genetics chromosomes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2010-AdG_20100317
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
NW1 1AT London
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.