Controlling the switch between centrosomes and cilia: how cells prevent ciliogenesis when it’s not required
Cilia are hair-like organelles that project from the surface of many cells. They act as signalling masts, housing receptors that are essential for communication and environmental sensing. The cilium consists of hundreds of components and many of them are required for cilium construction and maintenance. Cilia employ many of the same components as centrosomes and these two organelles are, in fact, mutually exclusive with only one type present in cells at any one time. Thus, switching between cilia and centrosomes is critical, particularly during the cell cycle. We identified BCAP as a dedicated ciliogenesis inhibitor and hypothesise that BCAP is a key intermediary linking ciliogenesis with proliferative control. This project will investigate the precise mechanism by which BCAP achieves inhibition, exploiting the expertise at Royal Holloway and Imperial. Roles in autophagy and vesicle trafficking will be tested. We will determine the protein partners of BCAP through proteomic studies. We will investigate how BCAP is subject to cell cycle control through phosphorylation by protein kinases known to control ciliogenesis using biochemical, proteomic and chemical genetic approaches. These experiments will uncover the roles and regulation of BCAP, elucidating the linkage between ciliogenesis and proliferative control, a fundamental aspect of human cell biology.
This PhD project will be supervised jointly by:
1. C.J.Wilkinson, Department of Biological Sciences, Royal Holloway University of London
2. David Mann, Department of Life Sciences, Imperial College London
Applicants are invited to contact supervisor(s) by email ahead of submitting their application. Further information about applying for a postgraduate course at Royal Holloway can be found here:
Applications should be submitted online:
Shortlisted eligible studentship applicants, will be notified within two-three weeks of the application deadline. Formal studentship interviews will usually be held within three-four weeks of the application deadline.
The funding for the project will cover home/EU tuition fees and a yearly stipend.
de Saram et al., 2016, BCAP is a centriolar satellite protein and inhibitor of ciliogenesis, Journal of Cell Science, 130, 3360-3373, doi:10.1242/jcs.196642
Stowe, TR, Wilkinson, CJ, Iqbal, A & Stearns, T (2012) The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium. Molecular Biology of the Cell. 23(17): 3322-35. doi:10.1091/mbc.e12-02-0134
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