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Towards a deep knowledge of the extracellular matrix proteins functions in the Duchenne Muscular Dystrophy

Objective

Healthy skeletal muscle has a powerful capacity to regenerate after an injury. On the opposite, muscular dystrophies (MDs) are devastating diseases where these regenerative capacities are overwhelmed and the muscle fibers are progressively replaced by fibrosis, leading to muscle loss and finally to death. Fibrosis is the final outcome of excessive production of molecules constituting the extracellular matrix (ECM). However, ECM alterations in MDs have been considered only as the result of muscle damage, the inflammatory response, or an unbalanced degradation/synthesis by fibroblasts. MYO_MATRIX is a 2-year project proposing a innovative point of view by shifting the focus to the extracellular environment, i.e. ECM, as an active partner impacting on muscle cell properties. The final goal is to decipher the role of ECM in skeletal muscle homeostasis and to define the molecular ECM components at work during MDs. Specific objectives include the combination of proteomics, transcriptomics, in situ 3D tissue analyses and ex-vivo functional cell experiments. Comparison of muscles in various conditions (normal, regenerating and dystrophic) will define key molecular determinants controlling beneficial ECM remodeling (in healthy regenerating muscle) versus detrimental fibrosis (in dystrophic muscle). The transdisciplinary (biochemistry and biology) and multilevel (protein, mRNA, cell, tissue) approach will identify new components in MDs. Such an outside-in approach has never been tested so far in skeletal muscle. The project, implemented by a biochemist researcher in a biology host lab (Universit Claude Bernard Lyon 1 at Institut NeuroMyoGne), will identify the molecular alterations of ECM in MDs and how they affect the behavior of cells that contribute to muscle homeostasis. The identification of the ECM molecular determinants is the ambition of the project, to propose therapeutic targets for MD patients for whom an effective treatment does not exist yet.

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Programme(s)

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Topic(s)

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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-2022-PF-01

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Coordinator

UNIVERSITE LYON 1 CLAUDE BERNARD
Net EU contribution

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.

€ 195 914,88
Address
BOULEVARD DU 11 NOVEMBRE 1918 NUM43
69622 Villeurbanne Cedex
France

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Region
Auvergne-Rhône-Alpes Rhône-Alpes Rhône
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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