PhD Research Project: Mechanisms of cell signalling and coordination of cell polarity in animal dev
Tissue morphogenesis, repair and regeneration requires cells to communicate and coordinate their behaviours. Major pathways involved are the Wnt/Frizzled and Fat/Dachsous planar polarity pathways that mediate polarised cell signalling in epithelia sheets. Loss of their activity leads to a variety of developmental abnormalities in animal models such as failure of neural tube closure, cleft palates and heart defects, as well as deficits in wound healing and failure to repair kidney damage resulting in polycystic tubules, and is also implicated in cancer metastasis.
The project will focus on understanding molecular mechanisms of Wnt/Frizzled and Fat/Dachsous pathway activity, and in particular how individual proteins adopt polarised distributions with cells, and the signalling mechanisms that propagate this polarity from cell to cell. A molecular genetic approach will be used, taking advantage of the well-established model Drosophila, which provides sophisticated molecular and genetic and cell biological tools. A major focus in the lab is understanding protein dynamics during cell signalling, using techniques such as live imaging (both conventional and super-resolution) and FRAP, and combining this with genetic screens to identify new pathway components and cell biology and biochemical studies of protein behaviours. We combine these experimental studies with computation modelling approaches to aid in experimental design and hypothesis testing.
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*.
Hale, R., Brittle, A.L., Fisher, K.H., Monk, N.A. and Strutt, D. (2015) Cellular interpretation of the long-range gradient of Four-jointed activity in the Drosophila wing. eLife 4, e05789. [PMC4338440]
Strutt, H.*, Searle, E.*, Thomas-MacArthur, V., Brookfield, R. and Strutt, D. (2013) A Cul-3-BTB ubiquitylation pathway regulates junctional levels and asymmetry of core planar polarity proteins. Development 140: 1693-1702. [PMC3621487]
Brittle, A., Thomas, C. and Strutt, D. (2012) Planar polarity specification through the asymmetric subcellular localisation of the atypical cadherins Fat and Dachsous. Current Biology 22: 907-914. [PMC3362735]
Strutt, H.*, Warrington, S.J.* and Strutt, D. (2011) Dynamics of core planar polarity protein turnover and stable assembly into discrete membrane subdomains. Developmental Cell 20: 511-525. [PMC3094756]