Objective
Protection of genome integrity is crucial for maintaining cell identity and viability. However, the organisation of DNA with histone proteins into chromatin in eukaryotic cell nuclei poses structural constraints to the detection and repair of DNA lesions. Dynamic and tightly controlled changes in chromatin organisation are thus critical for an efficient response to DNA damage, while at the same time preserving chromatin integrity. Yet, the underlying regulatory mechanisms are still poorly characterised, particularly in higher eukaryotes.
Here, we describe a range of complementary approaches using cutting-edge imaging to address this issue in mammalian cells. Our aim is to investigate DNA damage-induced alterations at distinct levels of chromatin organisation, from histone proteins up to higher-order chromatin structure, and to explore the underlying mechanisms.
(1) We first intend to provide a detailed analysis of histone variant dynamics at DNA damage sites by combining local induction of DNA lesions with pulse-chase imaging of histone proteins. (2) To examine how these dynamics are reflected at the level of higher-order chromatin folding, we will quantitatively visualise changes in chromatin compaction in cells exposed to genotoxic stress. For this, we will implement a recent FLIM-FRET-based approach and also exploit super-resolution fluorescence microscopy. (3) We will examine the spatio-temporal regulation of damaged chromatin reorganisation, analyse how it connects with DNA damage signalling and repair pathways, and characterise the histone chaperones and chromatin remodelling factors involved. (4) To broaden the range of candidate regulatory factors, we will screen for novel players in the DNA damage response among chromatin-associated proteins using laser micro-irradiation induced damage.
Altogether, these integrated approaches should provide new insights into the molecular mechanisms that coordinate the maintenance of genome and epigenome integrity.
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 genetics DNA
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics genomes
- natural sciences physical sciences optics laser physics
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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-2013-StG
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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
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.