Objective
Homologous recombination (HR) is an essential DNA repair mechanism and defects in different HR factors are linked with disease and cancer pre-disposition. The RAD51 recombinase plays a central role in HR, forming nucleoprotein filaments at sites of DNA damage and promoting homologous pairing and DNA strand exchange. RAD51 filament formation is mediated by the BRCA2 tumour suppressor, mutations in which lead to a high incidence of developing breast cancer. BRCA2 interacts with other HR factors, such as PALB2 and members of the RAD51 paralog family. Many of these proteins also function as tumour suppressors. The host laboratory has purified full-length BRCA2 protein and shown that it facilitates RAD51-mediated HR by acting as a molecular chaperone for RAD51 filament formation. This offers a unique position to extend our understanding of pre-recombinational protein assembly by inclusion of additional critical HR factors, and answer the important question how PALB2 and the RAD51 paralogs coordinate their activities with BRCA2 to promote the assembly of RAD51 filaments. To achieve this, I propose to:
i) Characterize the biochemical and structural properties of RAD51 paralog complexes
ii) Define the interplay between BRCA2, PALB2, and the RAD51 paralogs in forming pre-recombination complexes for RAD51 assembly, using biochemical approaches and electron microscopic visualisation.
Given the importance of HR and its role in tumour avoidance, I anticipate our results to provide significant new insights into the molecular mechanisms underlying genome instability. Also, they may uncover novel targets for therapeutic intervention for breast cancer. Together, the proposed research will not only substantially advance knowledge of DNA repair but will also provide me with invaluable training in biochemistry, electron microscopy and project management in a world-class research environment. As such, it forms the perfect platform from which to launch my independent research career.
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 breast cancer
- natural sciences biological sciences molecular biology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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.
(opens in new window) H2020-MSCA-IF-2014
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
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.