Project description
Insight into the nuclear diversity of muscle
Muscle fibres are an example of syncytial cells where individual muscle cells are joined together to improve structural stability and facilitate the contraction of the entire fibre. Funded by the European Research Council, the SyncyNucDiff project will address a fundamental question in syncytia biology: how do these cells organise gene expression among the different nuclei? Previous work has indicated great diversity in the transcriptional programme of each myofibre nucleus. To understand how these identities are maintained, researchers will focus on the role of chromatin architecture and transcriptional regulators. Project results and the innovative tools created will pave the way for studying the pathophysiology of syncytia cells in the near future.
Objective
Due to their cellular anatomy, syncytial cells face many unique challenges that mono-nucleated cells do not. One of them is how syncytial cells organize gene expression among many nuclei in a shared cytoplasm. How such property is linked to their biological functions remains poorly understood. Using the skeletal muscle as a paradigm and single-nucleus transcriptomics, I recently uncovered previously unrecognized diversity and dynamics of myonuclear transcriptional programs. This conceptualized the syncytial muscle cell itself as an analog of multi-cellular tissue where individual nuclei are counterparts of differentiated cell types. My findings raise two important and unanswered questions. 1) How are the diverse nuclear identities specified and maintained? And 2) What are the functional contributions of the diverse nuclear subtypes in health and disease? I will first focus on the nuclei at the neuromuscular junction (NMJ) and myotendinous junction (MTJ), which are responsible for initiation of contraction and dissipation of contractile force, respectively. Despite their well-established functions, the mechanisms that specify or maintain them are sparsely understood. I will investigate how chromatin architecture and transcriptional regulators govern their identities. I will then characterize the upstream signalling pathways from motor neuron or tendon cells that activate the specific transcriptional programs. So far, genetic manipulation of myofibers have targeted entire muscle nuclei. To overcome this limit, I will develop tools that allow genetic manipulation in specific nuclear subtypes. Previous works had identified a new nuclear subtype associated with muscular dystrophy and a transient time window during postnatal development. I will characterize the function of these nuclei using a method that abolishes their transcriptional activities. The approaches to be developed here will pave the way to understanding the pathophysiology of syncytial cells in the future.
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.
- medical and health sciences basic medicine anatomy and morphology
- medical and health sciences basic medicine physiology pathophysiology
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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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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.
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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-ERC - HORIZON ERC Grants
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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-2021-STG
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75654 PARIS
France
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