About the Project
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 called satellite cells. Satellite cells are quiescent in healthy muscles, and maintaining quiescence is essential for skeletal muscle homeostasis. However, upon injury, satellite cells become activated and enter the cell cycle to produce progenitor cells that differentiate to repair damaged fibers. A subset of progenitor cells return to quiescence to maintain a pool of stem cells for future use. Cell signalling plays a key role in controlling the balance between proliferation, differentiation and self-renewal (ability to maintain a stem cell pool). 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 Hedgehog signalling pathway in controlling quiescence and cell cycle progression in satellite cells. We have also genetic evidence suggesting that cell cycle progression may impact on cell fate decision, namely differentiation versus self-renewal. However, the mechanisms by which Hedgehog signalling coordinates cell cycle progression in satellite cells and their role in skeletal muscle regeneration remain to be elucidated. This project consists in uncovering the mechanisms by which Hedgehog signalling controls cell cycle progression and skeletal muscle regeneration. The project will provide training in stem cell biology (culture), molecular techniques (CRISPR-Cas9 mutation, qPCR), imaging (confocal microscopy), and genetics (conditional knockout mouse lines).
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 www.sheffield.ac.uk/sgs to learn more.
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 using the following link: http://www.sheffield.ac.uk/postgraduate/research/apply/applying
All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information.
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: https://doi.org/10.1101/2019.12.21.884601
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.