Project description
Understanding the connection between chromatin and DNA repair
Depending on its needs, a cell can alter the structure of its chromatin from a condensed, inactive form to a less condensed, active state, and vice versa. This reversible nature of chromatin shapes gene regulation and cellular differentiation. Funded by the Marie Skłodowska-Curie Actions programme, the XICUT project aims to investigate the DNA damage response within chromatin and how that affects DNA repair. Researchers will focus on the inactive X chromosome in female mammals, exploring how its chromatin state reacts to DNA double-strand breaks. The work will provide important insights into repair mechanisms and chromatin dynamics.
Objective
The DNA damage response takes place on a chromatin substrate and triggers profound chromatin alterations. Chromatin states vary substantially between genomic regions, driving distinct gene expression profiles and also different DNA damage repair responses. One striking example is the heterochromatinization of an entire chromosome, the inactive X chromosome in female mammals, that is silenced during embryonic development by facultative heterochromatin formation. How the facultative heterochromatin state of the inactive X responds to DNA damage and impacts DNA repair is poorly understood. My research project aims at identifying chromatin changes that accompany the repair of the most cytotoxic form of DNA damage, DNA double-strand breaks (DSBs), in facultative heterochromatin and the mechanisms that ensure the establishment and maintenance of the inactive X chromosome in response to DNA damage in mammalian cells. To generate DSBs, I use the CRISPR/Cas9 technology that allows sequence-specific targeting of the Cas9 nuclease. Thanks to available bioinformatic tools, I can discriminate between active and inactive X chromosomes, analyze the genomic instability profiles induced around the break sites and decipher the repair pathway involved. In parallel, I will profile the chromatin marks associated with the inactive X chromosome in the vicinity of DSBs to assess the impact of DNA damage and repair on heterochromatin maintenance. Moreover, I will test the hypothesis that the high level of replicative stress-induced breaks in embryonic stem cells could drive heterochromatin establishment and thus skew the choice of the inactive X chromosome. For this, I will study the impact of generating DSBs on one X chromosome of mouse stem cells on their differentiation potential and their propension to inactivate the damaged X chromosome. Together, this work should shed light on the interplay between the DSB response and facultative heterochromatin states.
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 genetics DNA
- natural sciences biological sciences genetics epigenetics epigenomes
- natural sciences biological sciences zoology mammalogy
- natural sciences biological sciences genetics chromosomes
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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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2022-PF-01
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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.
75794 PARIS
France
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.