Objective
During mammalian development, precise gene expression patterns have to be established and then maintained, or reversed, in different cellular and tissue contexts. A striking example of such developmentally regulated gene control is X-chromosome inactivation (XCI), whereby one of the two X chromosomes in females is silenced during embryogenesis. XCI is initiated by the non-coding Xist RNA, which coats the chromosome in cis, triggering gene repression, chromatin changes and chromosomal reorganisation. Although Xist’s regulation has been investigated intensively, less is known about the actual mechanisms underlying the process of chromosome-wide gene silencing that it induces. Indeed, X-linked loci show very different kinetics of repression during development, implying regional and/or locus specific diversity. Furthermore, some genes avoid or escape XCI altogether, either constitutively or in a tissue or stage-specific fashion, but the molecular basis for this is unclear. Here we propose to dissect the mechanisms underlying gene regulation during XCI. We will investigate the roles of recently identified Xist partners in gene silencing and perform genetic screens to identify new factors involved in silencing and escape from XCI. Transcription, chromatin status and chromosome conformation during XCI will be investigated in an allelic-specific manner during precise developmental time windows to pinpoint the critical changes accompanying silencing and escape. We will use genetic engineering to alter genomic and epigenomic landscapes of selected loci and target candidate trans-acting factors to their putative regulatory elements. Finally, we will develop tools to explore gene expression during XCI using live cell imaging of embryogenesis. Using this innovative set of approaches, we hope to define both general principles underlying gene silencing and escape in XCI, as well as locus-specific features that could serve as new paradigms for research in developmental epigenetics.
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 biomolecules proteins
- natural sciences biological sciences developmental biology
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences genetics genomes
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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.
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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-ADG - Advanced 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-2014-ADG
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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.
69117 Heidelberg
Germany
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.