Molecular mechanisms of stem cell function in skeletal muscle ageing

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 cell proliferation, cell differentiation and self-renewal (ability to maintain a stem cell pool) in skeletal muscle stem cells. Defects that disrupt this balance causes a decline in regenerative capability and leads to ageing. In previous work, we have reported that a microtubule-containing organelle at the surface of cells called the primary cilium plays a critical role in mediating signalling pathways that control the activity of skeletal muscle stem cells. However, the importance of this organelle and cell signalling pathways in aging remains to be established.

This project consists in using a combination of mouse genetic models and in vitro cell culture systems to uncover the mechanisms by which skeletal muscle stem cell activity decline during ageing. In a supportive, yet hard-working environment, you will be trained to the various cutting-edge techniques required for the project, including advanced training in stem cell biology (culture), molecular techniques (CRISPR-Cas9 mutation, qPCR), immunodetection experiments (immunofluorescence, western blot), imaging (confocal microscopy), next generation sequencing and mouse genetics (conditional knockout mouse lines).

You will be based in the School of Biosciences, which groups a large number of academics with international reputation and offers access to state-of-the-arts facilities.

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.