Control of skeletal muscle regeneration and aging by cell signalling

The ability of skeletal muscles to regenerate in response to injury, exercise, growth or disease depends on a population of adult skeletal muscle stem cells. With aging, the number and regenerative capacity of the stem cells declines; this contributes to the aging process and ultimately to the loss of muscle mass in elderly people. Cell signalling plays a key role in controlling the balance between proliferation, differentiation and self-renewal (ability to maintain a stem cell pool) in skeletal muscle stem cells. Defects that disrupt this balance contribute to disease progression in muscular dystrophies and to aging. In previous work, we have uncovered a critical role for the Sonic Hedgehog signalling pathway in controlling the activity of skeletal muscle stem cells. However, the importance of this cell signalling pathway in aging remains to be established. Likewise, the cellular process(es) implicated in stem cell aging remain to be elucidated.

This project consists in uncovering the mechanisms by which Sonic Hedgehog signalling controls skeletal muscle stem cells during muscle regeneration, and how disruption in Sonic Hedgehog signalling impacts muscle aging. The project will provide advanced training in stem cell biology (culture), molecular techniques (CRISPR-Cas9 mutation, qPCR), imaging (confocal microscopy), and genetics (conditional knockout mouse lines).