Project description
Dissecting the mechanisms of muscle growth
Muscle growth and long-term maintenance rely on a poorly understood cellular process in which muscle stem cells fuse into existing muscle fibres, adding new nuclei and cellular material. This process, known as myonuclear accretion, is essential for muscle adaptation throughout life, yet its molecular mechanisms remain largely unknown. The ERC-funded RegenerFuse project combines advanced live imaging, genetics and quantitative cell biology to uncover how this fusion is regulated. The team will identify key molecular regulators, dissect specialised fusion hotspots and test how these mechanisms impact muscle function in vivo. By linking molecular events to tissue physiology, RegenerFuse aims to reveal fundamental principles of muscle biology and provide a foundation for future therapeutic strategies.
Objective
Skeletal muscle fibers are highly organized multinucleated cells that grow and regenerate by fusing with myocytes derived from their resident stem cells. The fusion between myocytes and mature muscle fibers, which underpins the remarkable adaptability of muscles, is molecularly distinct from the fusion events that occur during development. This secondary fusion process, also known as myonuclear accretion, integrates mononucleated myocytes into immature myotubes or mature fibers, supporting muscle growth, repair, and regeneration throughout life. Despite its critical physiological importance, the mechanisms governing secondary fusion and the active role of myofibers in this process remain poorly understood.
Leveraging the development and application of high-content screening, advanced biochemistry, genetics, cell biology, transcriptomics, and cutting-edge imaging techniques, including 3D correlative light and electron microscopy (CLEM), we aim to provide groundbreaking insights into the molecular and cellular processes of secondary fusion. To achieve this, we will address three independent but interconnected aims:
Aim 1: Screen for regulators of secondary fusion and determine their effects using high-content imaging together with exploratory molecular studies.
Aim 2: Elucidate the molecular mechanisms and cellular dynamics underpinning fusion hotspots.
Aim 3: Establish the physiological relevance of myonuclear accretion in vivo by visualizing fusion hotspots and evaluating the impact of enhanced myoblast transplantation on muscle regeneration and function.
This synergistic approach will transform our understanding of muscle physiology, bridging the molecular mechanisms with their functional outcomes. The findings promise to uncover new principles of cell fusion, organelle dynamics, and tissue adaptability, offering profound implications for muscle biology and novel therapeutic strategies for muscle-wasting diseases.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
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-2025-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.
7610001 Rehovot
Israel
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