CORDIS - Forschungsergebnisse der EU
CORDIS

Metabolic regulation of reciprocal signalling between skeletal muscle cell types

Projektbeschreibung

Einzigartige Erkenntnisse über die Signalgebung zwischen Muskelfasern und Stammzellen

Der Erhalt der Skelettmuskelmasse und -qualität wird durch eine bemerkenswerte Plastizität des Gewebes ermöglicht. In den Muskeln ansässige Stammzellen tragen durch die Differenzierung und die anschließende Verschmelzung mit den Muskelfasern – einem Vorgang, der myonukleare Akkretion genannt wird – zu dieser Plastizität bei. Das Fortschreiten dieses Vorgangs wird von bestimmten Stoffwechselanforderungen dieser Stammzellen charakterisiert und hängt vom Stoffwechselzustand der Muskelfasern ab. Das EU-finanzierte Projekt MUSIC zielt darauf ab, die Rolle des Stoffwechselregulators AMPKalpha2 bei der Signalgebung der in den Muskeln ansässigen Stammzellen zu entschlüsseln. Außerdem wird die Forschung eine interdisziplinäre Zusammenarbeit anstoßen, um integrative phosphoproteomische und metabolomische Analysen durchzuführen. Ziel dieses Vorhabens ist es, einzigartige Erkenntnisse über die Signalgebung zwischen den Muskelfasern und den Stammzellen zu gewinnen.

Ziel

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.

Koordinator

UNIVERSITE LYON 1 CLAUDE BERNARD
Netto-EU-Beitrag
€ 184 707,84
Adresse
BOULEVARD DU 11 NOVEMBRE 1918 NUM43
69622 Villeurbanne Cedex
Frankreich

Auf der Karte ansehen

Region
Auvergne-Rhône-Alpes Rhône-Alpes Rhône
Aktivitätstyp
Higher or Secondary Education Establishments
Links
Gesamtkosten
€ 184 707,84