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Metabolic regulation of reciprocal signalling between skeletal muscle cell types

Project description

Gaining unique insight into the myofiber to MuSC signalling

Maintenance of skeletal muscle quantity and quality is facilitated by remarkable tissue plasticity. Muscle-resident stem cells (MuSC) contribute to this plasticity by the differentiation and subsequent fusion with the myofiber in the process called myonuclear accretion. The progression of this process is characterised by distinct MuSC metabolic requirements and depends on the myofiber metabolic state. The EU-funded MUSIC project aims to decipher the role of the metabolic regulator AMPKalpha2 in MuSC signalling. Furthermore, the research will initiate an interdisciplinary collaboration to perform integrative phosphoproteomic and metabolomic analyses to get a unique insight into the myofiber to MuSC signalling.

Objective

Maintenance of skeletal muscle quantity and quality is crucial for healthy aging, and is facilitated by a remarkable tissue plasticity. Muscle-resident stem cells (MuSC) provide an important contribution to this plasticity by differentiation and subsequent fusion with the myofiber – a process called myonuclear accretion. The progression of this process is characterised by distinct MuSC metabolic requirements, and seems to depend on the myofiber metabolic state. We therefore anticipate a role of metabolism – and specifically, the metabolic regulator AMPKalpha2 – in myofiber to the MuSC signalling, directing MuSC fate towards myonuclear accretion. We explore this in three aims, that constitute ‘proof of principle’, ‘target identification’, and ‘target validation’.
To achieve these aims, we ensure a two-way transfer of knowledge by combining my Cre/LoxP-based cell system, with the host lab’s primary MuSC isolation. These combined technologies also provide a platform to study myonuclear accretion in the context of other molecular targets and diseases. Furthermore, we will initiate an interdisciplinary collaboration to perform integrative phosphoproteomics and metabolomics, and get a unique insight in the myofiber to MuSC signalling. This will provide AMPKalpha2-targets that will be validated using advanced mouse models established at the host lab, and provides leads for research after the fellowship. Results will be communicated to a scientific and non-scientific audience by publication in scientific journals, conference presentations, via Twitter, workshops and open days.
Since the host lab is at the forefront of myogenesis research, it will provide me with an ideal environment to improve my scientific network, and receive the relevant technical and personal training. Together with the innovative nature and interdisciplinarity of the project, this will give me the unique opportunity to reach professional maturity both during and after the fellowship.

Coordinator

UNIVERSITE LYON 1 CLAUDE BERNARD
Net EU contribution
€ 184 707,84
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
Links
Total cost
€ 184 707,84