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).
This position is for self funded or externally funded students only.
First class or upper second 2(i) in a relevant subject.
To formally apply for a PhD, you must complete the University’s application form.
All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information.
Science Graduate School
As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit http://www.sheffield.ac.uk/sgs to learn more.
Cruz-Migoni SB, Mohd Imran K, Wahid A, Rahman O, Briscoe J, Borycki AG.
A switch in cilia-mediated Hedgehog signaling controls muscle stem cell
quiescence and cell cycle progression. BioRxiv doi:
Jaafar Marican NH, Cruz-Migoni SB, Borycki AG (2016). Asymmetric
Distribution of Primary Cilia Allocates Satellite Cells for Self-Renewal. Stem
Cell Reports. 6(6):798-805.