Project description
Cell control in salamander heart regeneration
Salamanders have an incredible ability to precisely regenerate complex structures, but it’s unclear how they control this process at the cellular level. Technical challenges in studying high-resolution cellular events and linking cell behaviour with tissue function have hindered progress. The ERC-funded Tightly Controlled project will create a comprehensive view of regeneration by combining gene editing, deep-tissue imaging and spatial omics. The research team will use Pleurodeles waltl as a model to study heart regeneration and evaluate the role of tight junctions and mechanical signals in cellular event coordination. Project findings can have implications for regenerative medicine and cancer research.
Objective
One of the most fascinating aspects of salamander regeneration is the level of precision at which restoration of complex structures occurs. How the recovery of form and function is sensed at a cellular level leading to appropriate termination of regenerative programs remains largely unknown. This is partly due to technical challenges of studying cellular events at a high-resolution during regeneration and establishing a constitutive link between cell behavior, tissue architecture and function. Here, I propose taking an interdisciplinary approach that combines gene editing, deep-tissue imaging, force measurements and spatial -omics to overcome these barriers. My goal is to gain holistic understanding of regeneration by integrating molecular, cellular, mechanical and functional parameters. Specifically, I aim to explore the role of tight junctions and mechanical cues in sensing and relaying macroscale information to adapt cellular events as the regeneration unfolds. We will utilize the newt Pleurodeles waltl and heart regeneration as an ideally suited regeneration context where I recently showed that the injury response by the epithelial-like covering called epicardium and the dedifferentiating cardiomyocytes are closely coordinated to replenish the lost muscle. By combining long term intravital cell tracking, mechanical characterization and ultrasound imaging with tight junction manipulations and mechanical perturbations we will 1) define cell dynamics and regenerative state transitions 2) test whether unique expansion in the tight junction protein Claudin-6 sequence that extends its N-terminus is protective against overproliferation and 3) map the physical properties controlling the termination of regenerative programs. Our results will identify mechanisms underlying the tight control of regeneration and bring new insights into the function of Claudins that are frequently dysregulated in cancer, opening new venues in regenerative medicine and cancer research.
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.
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
- medical and health sciences clinical medicine oncology
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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.1.1 - 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.
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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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(opens in new window) ERC-2024-STG
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171 77 STOCKHOLM
Sweden
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