Phd contract in the field of Medical sciences financed for three years by the University of Clermont Auvergne

Characterisation of the mechanisms of regulation of myogenesis by the epigenetic enzyme TET

The development of the adult muscular system is a tightly regulated process which requires the coordinated deployment of a specific gene expression program. Accordingly, alterations in myogenic genes transcription and modifications of the epigenetic landscape underlie the aetiology of numerous neuromuscular disorders such as muscular dystrophies in humans. We gathered strong preliminary results showing that Drosophila TET, which codes for an epigenetic enzyme conserved in mammals,is required for proper gene expression in adult muscle progenitors and that it controls flight muscle development and function. Here, we propose to take advantage of the genetic tools available in Drosophila to tackle more precisely the role and mode of action of TET in muscle progenitor maintenance and differentiation.The PhD studentwill use a combination of state-of-the-art genetic, molecular, imaging techniques and behavioural assays to characterise TET function at different steps of their development: (1) in the larval AMPs, (2) in their differentiating progenies during pupariation, and (3) in differentiated adult muscles as well as in the recently described “satellite-like”muscle stem cells.

Rodrigues et al., Differential activation of JAK-STAT signaling reveals functional compartmentalization in Drosophila blood cell progenitors. eLife (2021) 10:e61409.

Fauquier et al.,CBP and p300 regulate distinct gene networks required for human primary myoblast differentiation and muscle integrity. Scientific Reports (2018) Aug 22;8(1):12629.