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Role of Hedgehog signalling in skeletal muscle regeneration

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

The ability of skeletal muscle to regenerate in response to injury, exercise, growth or disease depends on a population of stem cells called satellite cells. Hence, defects in satellite cell activity 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 the activity of satellite cells, in particular the balance between proliferation, differentiation and self-renewal (ability to maintain a stem cell pool). However, the molecular targets of Hedgehog signalling in satellite cells remain unknown.
To address this question, whole-genome transcriptome analyses were carried out and identified a number of putative target genes. This project consists in uncovering the mechanisms by which Hedgehog signalling controls satellite cell activity by characterizing some of the target genes identified and determining their function in satellite cells and 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 http://www.sheffield.ac.uk/sgs to learn more.

Funding Notes

Entry requirements
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: View Website

*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

• Rayagiri SS, Ranaldi D, Mohamad Azhar I, Raven A, Lefebvre O, Zammit P, and Borycki AG. (2018) Laminin-111 deposition in the satellite cell niche mediates satellite cell self-renewal during skeletal muscle regeneration. Nature Communications 9:1075.
• 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#tab01

Related Subjects

How good is research at University of Sheffield in Biological Sciences?

FTE Category A staff submitted: 44.90

Research output data provided by the Research Excellence Framework (REF)

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