PhD Research Project: Role of primary cilia in skeletal muscle stem cells and muscle regeneration.
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.
This project aims at investigating further the role of primary cilia in satellite cell 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 whether primary cilia are essential cues for asymmetric cell division and stem cell self-renewal, and to establish the molecular mechanisms controlled by primary cilia in muscle regeneration.
Applications from self-funded students or students with secured funding are also welcome.
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD Studentship, you must complete the University's application form using the following link: http://www.sheffield.ac.uk/bms/prospective_pg/how_to_apply
*All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information*.
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.
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