Objective
Cancer and other diseases are driven by genomic alterations initiated by DNA breaks. Within our genomes, some regions are particularly prone to breakage, and these are known as common fragile sites (CFSs). CFSs are present in every person and are frequently sites of oncogenic chromosomal rearrangements. Intriguingly, despite their fragility, many CFSs are well conserved through evolution, suggesting that these regions have important physiological functions that remain elusive. My previous background in genome editing, proteomics and replication-born DNA damage has given me the tools to propose an ambitious and comprehensive plan that tackles fundamental questions on the biology of CFSs. First, we will perform a systematic analysis of the function of CFSs. Most of the CFSs contain very large genes, which has made technically difficult to dissect whether the CFS role is due to the locus itself or to the encoded gene product. However, the emergence of the CRISPR/Cas9 technology now enables the study of CFSs on a more systematic basis. We will pioneer the engineering of mammalian models harbouring large deletions at CFS loci to investigate their physiological functions at the cellular and organism levels. For those CFSs that contain genes, the cDNAs will be re-introduced at a distal locus. Using this strategy, we will be able to achieve the first comprehensive characterization of CFS roles. Second, we will develop novel targeted approaches to interrogate the chromatin-bound proteome of CFSs and its dynamics during DNA replication. Finally, and given that CFS fragility is influenced both by cell cycle checkpoints and dNTP availability, we will use mouse models to study the impact of ATR/CHK1 pathway and dNTP levels on CFS instability and cancer. Taken together, I propose an ambitious, yet feasible, project to functionally annotate and characterise these poorly understood regions of the human genome, with important potential implications for improving human health.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences biochemistry biomolecules nucleic acids
- medical and health sciences medical biotechnology genetic engineering gene therapy
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics genomes
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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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
ERC-STG - Starting Grant
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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) ERC-2015-STG
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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.
28006 MADRID
Spain
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.