Project description
Genome folding and gene transcription
Transcription, the process of copying DNA into RNA, is initiated at promoters, DNA elements that recruit the transcription machinery. The rate and specificity of transcription is increased by enhancers, distal regulatory DNA elements that serve as hubs for transcription factors and coactivators. Despite years of investigation, it remains unclear whether promoter-enhancer cooperation plays an instructive role in transcription. With the support of the Marie Skłodowska-Curie Actions programme, the DynaMitE project will investigate the role of these elements during the transition from mitosis to interphase, when chromatin reorganises and gene expression is reset. Researchers will employ live imaging and genome engineering to monitor how genome folding influences transcription reactivation.
Objective
In spite of intense investigations, it remains unclear whether and how the interaction between promoters and distant enhancers has an instructive role in transcription. I will tackle this question by tracking the spatial and temporal dynamics of gene regulatory sequences alongside nascent transcription during the critical biological event that is the mitosis-to-interphase transition in live cells. During mitosis, chromatin undergoes a massive reorganization, resulting in the loss of long-range interactions, the displacement of transcription factors, and a global reduction in transcription. The re-establishment of interphase gene expression programs is essential for the maintenance (or a chance for the change) of cell identity; however, the molecular mechanism of such re-establishment is an unsolved biological problem. Previous studies, largely relying on fixed cells and next-generation sequencing technologies, have not captured the dynamic nature of these events. I will use state-of-the-art genome engineering and live imaging technologies in proliferating mouse embryonic stem cells to simultaneously monitor the movement of regulatory sequences and the re-initiation of transcription at key pluripotency genes at the exit from mitosis, as well as test the role of mitotically-retained transcription factors. This project, termed DynaMitE, will address the burning question of how genome folding influences transcription within a physiological context of transcription re-activation, and will uncover mechanistic insights into the restoration of interphase gene expression with unparalleled temporal resolution in single cells.
Importantly, by achieving the objectives of DynaMitE within the host laboratory, I will complement my expertise in genomics and developmental biology with advanced skills in cutting edge microscopy, image analysis and a biophysical lens on gene regulation, shaping the profile of the future group leader I aspire to be.
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 physical sciences optics microscopy
- natural sciences biological sciences genetics genomes
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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)
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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75724 Paris
France
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