Descripción del proyecto
Obtención de información única sobre la señalización de la miofibra a las células madre musculares
El mantenimiento de la cantidad y calidad del músculo esquelético se ve favorecido por la notable plasticidad de los tejidos. Las células madre musculares (MuSC, por sus siglas en inglés) contribuyen a esta plasticidad mediante la diferenciación y posterior fusión con la miofibra en un proceso denominado acreción mionuclear. La evolución de este proceso se caracteriza por distintos requisitos metabólicos de las MuSC y depende del estado metabólico de la miofibra. El objetivo del proyecto MUSIC, financiado con fondos europeos, es descifrar el papel del regulador metabólico AMPKalpha2 en la señalización de las MuSC. Además, la investigación comenzará una colaboración interdisciplinar para la realización de análisis fosfoproteómicos y metabolómicos integradores que logren una información única sobre la señalización de la miofibra a las MuSC.
Objetivo
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.
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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
69622 Villeurbanne Cedex
Francia