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Metabolic regulation of reciprocal signalling between skeletal muscle cell types

Description du projet

Mieux comprendre le rôle des myofibres dans la signalisation des cellules souches musculaires

Le maintien de la quantité et de la qualité des muscles squelettiques est facilité par une plasticité tissulaire remarquable. Les cellules souches musculaires (MuSC pour «muscle-resident stem cells») contribuent à cette plasticité par la différenciation et la fusion ultérieure avec les myofibres dans le cadre d’un processus appelé accrétion myonucléaire. L’évolution de ce processus est caractérisée par différentes exigences métaboliques des MuSC et dépend de l’état métabolique des myofibres. Le projet MUSIC, financé par l’UE, entend déchiffrer le rôle du régulateur métabolique AMPKalpha2 dans la voie de signalisation des MuSC. En outre, les recherches lanceront une collaboration interdisciplinaire pour effectuer des analyses métabolomiques et phosphoprotéomiques intégratives afin de mieux comprendre les myofibres dans le cadre de la signalisation des MuSC.

Objectif

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.

Coordinateur

UNIVERSITE LYON 1 CLAUDE BERNARD
Contribution nette de l'UE
€ 184 707,84
Adresse
BOULEVARD DU 11 NOVEMBRE 1918 NUM43
69622 Villeurbanne Cedex
France

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Région
Auvergne-Rhône-Alpes Rhône-Alpes Rhône
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 184 707,84