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Role of primary cilia in skeletal muscle stem cells and muscle regeneration.


Department of Biomedical Science

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Dr A G Borycki Applications accepted all year round Self-Funded PhD Students Only

About the Project

Primary cilia are ancient organelles present at the surface of many cell types in vertebrates. In recent years, they have been shown to play essential roles in relaying sensory and signalling information from the environment to the cell. The importance of primary cilia is underscored by the growing family of diseases associated with defects in cilia function, known as ciliopathies.
Satellite cells are skeletal muscle-specific stem cells responsible for the post-natal growth and repair following injury of skeletal muscles. Satellite cells are normally quiescent, but proliferate and differentiate to repair muscles when they become activated. We have previously shown that quiescent satellite cells exhibit primary cilia, which are rapidly disassembled upon satellite cell activation. Interestingly, we uncovered that in later phases of muscle regeneration, primary cilia re-assemble exclusively at the surface of self-renewing satellite cells and are essential for the maintenance of a stem cell pool in muscles. Furthermore, recent work from the laboratory demonstrated a critical role for primary cilia in the control of the Hedgehog signalling pathway, and its control of satellite cell quiescence and self-renewal.
This project aims at investigating further the role of primary cilia in satellite cell quiescence and self-renewal, and in muscle regeneration. The project will use a well-established ex-vivo culture system of skeletal muscle fibres as well as in vivo genetic approaches in vertebrates, imaging and molecular biology approaches to investigate the mechanism by which primary cilia control both satellite cell quiescence and self-renewal. Such studies will provide valuable knowledge for furthering our understanding of muscle regeneration, and a framework for future work aiming at enhancing muscle regeneration.

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.

Funding Notes

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.

References

Reference:
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.

URL: https://www.sheffield.ac.uk/bms/research/borycki
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