Project description
Insight into gene expression regulation during development
The development of a complex organism from a single fertilised egg requires thousands of genes to be switched on and off in precise sequences across space and time. This is orchestrated by regulatory DNA elements called enhancers, which interact with genes across large genomic distances. How this communication is established and maintained during development remains poorly understood. With the support of the Marie Skłodowska-Curie Actions programme, the TempoEP project aims to investigate the mechanisms controlling enhancer-gene communication during mammalian embryogenesis. By combining genomic and imaging technologies, researchers will map how regulatory elements interact during development and how this translates into gene expression.
Objective
Embryonic development requires the coordinated execution of sequential gene expression programmes in space and time. This complex regulation is achieved by enhancers, cis-regulatory elements that relay spatiotemporal regulatory information to target promoter(s) in response to transcription factor (TF) binding. While enhancers (E) and promoters (P) are often separated by large linear genomic distances, they can come into close 3D proximity through E-P contacts. However, the mechanisms regulating the temporal dynamics of E-P communication and transcription remain elusive. In the nucleus, chromatin is folded by loop extrusion; disrupting this process abrogates large-scale architecture, yet has only minor effects on E-P contacts and gene expression. Also, the contribution of TFs bound at enhancers and promoters to E-P communication is still unclear. Importantly, previous studies mostly investigated these mechanisms in model systems where chromatin structure and transcription are at steady state, thus neglecting their dynamics. This proposal aims to investigate the causal role of loop extrusion and TF binding in the temporal dynamics of E-P communication and transcription during mammalian embryogenesis, using gastruloids (cultured pseudo-embryos) as a paradigm. This will be achieved through two objectives: (1) mapping how E-P contacts, TF occupancy and transcription evolve over developmental time; and (2) perturbing loop extrusion and TF occupancy with targeted protein degradation at specific developmental time windows. As a readout, I will combine genomic and imaging technologies. Genomics will provide a genome-wide view of changes in E-P contacts and transcription averaged across cells, while imaging will determine at selected loci whether these changes co-occur within individual nuclei. The mechanistic insights revealed by this dual approach will have broad implications for understanding gene regulation in both physiological and pathological developmental processes.
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
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences developmental biology
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2025-PF
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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.
75005 Paris
France
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