Project description
Deciphering the mechanisms underlying propagating epigenetic chromatin states
The propagation of chromatin’s information despite the complexity of DNA replication and mitosis is necessary for heritable changes in gene function, the ‘epigenetic inheritance’ of phenotypes, for example during the development of multicellular organisms. Histones and other proteins interact with chromatin during cell division and play important roles. For example, inheritance of parental histones is required to maintain epigenetic information and cellular identity. The ERC-funded ChromaDYN project will attempt to capture the dynamics of protein populations with high-tech experimental methods to capture protein-protein interaction networks and chromatin maps. Quantitative insights will be used to develop mathematical models of these dynamics with the ultimate goal of deciphering the mechanisms for propagating epigenetic chromatin states.
Objective
Chromatin packages the eukaryotic genome in a highly dynamic fashion, with dramatic structural changes during every cell cycle. At the same time, chromatin provides remarkable stability for transcriptional regulation and genome organization, for example in maintaining gene expression programs and lineage identity during complex organismal development. A mechanism to propagate information through ‘disruptive’ transitions in the cell cycle, namely DNA replication and mitosis, is key in maintaining heritable, so-called ‘epigenetic’ chromatin states.
Proteins that build and interact with chromatin, foremost histones, are much more than static architectural components. This motivates the development of time-resolved quantitative assays in the living cell, which will allow to capture dynamic features of chromatin states over timescales from minutes to days. Building on a synthetic biology toolbox, a quantitative multimodal pulse-and-label strategy will be developed. Following protein populations in both time and subcellular/genomic space, dynamic protein-protein interaction networks and chromatin maps will be captured.
The project will use to state-of-the-art quantitative biochemical, imaging, genomics and proteomics readouts, including single-cell readouts. These will feed into mathematical models to describe the dynamics and potential heterogeneity/stochasticity of the system under study, predict its response to perturbations and guide mechanistic hypotheses. The project will systematically decipher mechanisms for propagating epigenetic chromatin states, starting with the fundamental rules of histone inheritance through replication and mitosis. Additional levels of complexity introduced through chromatin remodeling activities, nucleosome turnover and histone exchange will be integrated. Finally, the dynamics underlying developmental chromatin state transitions, including asymmetric cell fate decisions, will be resolved.
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 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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HORIZON.1.1 - European Research Council (ERC)
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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
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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.
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-COG
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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.
171 77 STOCKHOLM
Sweden
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.