Descrizione del progetto
Acquisire informazioni uniche sulla miofibra per la segnalazione delle MuSC
Il mantenimento della quantità e della qualità del muscolo scheletrico è agevolato dalla notevole plasticità dei tessuti. Le cellule staminali residenti nei muscoli (MuSC, Muscle-resident Stem Cells) contribuiscono a questa plasticità attraverso la differenziazione e la conseguente fusione con la miofibra in un processo definito accrescimento mionucleare. La progressione di questo processo è caratterizzata da distinti requisiti metabolici delle MuSC e dipende dallo stato metabolico della miofibra. Il progetto MUSIC, finanziato dall’UE, si propone di decifrare il ruolo del regolatore metabolico AMPKalpha2 nella segnalazione delle MuSC. Inoltre, la ricerca avvierà una collaborazione interdisciplinare per eseguire analisi fosfoproteomiche e metabolomiche integrative per ottenere informazioni uniche sulla miofibra per la segnalazione delle MuSC.
Obiettivo
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.
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
69622 Villeurbanne Cedex
Francia