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SKeletal Muscle - REgulation of FORce and Maturation through Tubulin isotypes

Project description

Tubulin isotypes: code carriers for structure and function of microtubule networks

Patterned microtubule networks in muscle cells provide structural support, facilitate organelle movement, and help maintain muscle fibre integrity, particularly under mechanical stress. They are essential for muscle development and function. These networks are highly dynamic. Dysfunction of microtubule networks is linked to various muscular dystrophies. With the support of the Marie Skłodowska-Curie Actions programme, the SKM-REFORMAT project aims to investigate whether the tubulin isotypes in the network encode microtubule properties and patterns. Using in vitro tools, animal models, and state of the art microscopy, SKM-REFORMAT will investigate the effects of selected tubulin isotypes on structure and function, from macroscopic phenotypes to molecular mechanisms in health and disease.

Objective

Microtubules are formed by polymerization of tubulin heterodimers. Tubulin monomers rise from 16 genes each with their own spatiotemporal signature, resulting in a patterned microtubule network. As tubulin dimers define binding microtubule associated proteins (MAPs) and occurring post-translational modifications (PTMs), I wonder whether microtubule properties and patterns are encoded/defined by the tubulin isotypes themselves. This proposal aims at 1-confirmation of the expressed tubulin isotypes in skeletal muscle, depending on developmental stages, sex, and fiber type. 2-Understanding of how tubulin isotypes contribute to macroscopic phenotypes such as myoblasts fusion, general fiber organization and muscle contraction. 3-Deciphering of the molecular mechanisms at play upon tubulin isotype loss-of-function. 4-Assessement of potential beneficial effects of tubulin loss-of-function in diseases such as Duchenne muscular Dystrophy (DMD), Centronuclear Myopathy (CNM), and myasthenia. Using innovative in vitro differentiation tools, animal models and state of the art microscopy, I will explore all potential effects of selected tubulin isotypes, from macroscopic phenotypes to molecular mechanisms, as well as in disease. Expected techniques to use are: RT-q-PCR, co-cultures motoneurons-myoblasts, CRISPR/Cas9 mediated KO, shRNA KD, gene transfer by AAV injection, force measurement in vivo and ex vivo, immunohisto- and cytochemistry, live-imaging with fluorescent probes, and image analysis. Microtubule and tubulin being involved in many types of diseases (cancer, development, degeneration…) this project will lead to many economic, social and therapeutic benefits.

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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-2024-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.

€ 242 260,56
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

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