PhD Research Project: Cell plasticity in development and disease

Location
Sheffield, United Kingdom
Salary
Competitive
Posted
Jan 10, 2019
Closes
Feb 09, 2019
Ref
97028
Contract Type
Full Time
Job Type
PhD / Doctoral

Details

Although 90% of cancer deaths are caused by metastasis, the underlying pathogenic mechanisms are poorly understood. Cell plasticity is the ability of cells to reversibly change their phenotype and plays a critical role at multiple steps in the complex process of tumour dissemination, which relies on cells undergoing an epithelial-to-mesenchymal transition (EMT), migrating away from the primary tumour and later undergoing a reverse mesenchymal-to-epithelial transition (MET). While several transcription factors that regulate EMTs have been isolated, how these actually impinge on the cellular responses underlying cell plasticity remains poorly understood. Even less is known about MET: we have so far failed to identify the signals required for its induction, nor do we understand how it occurs at the cell and molecular level.

We are looking for a PhD student to work on a project targeted towards identifying the molecular mechanisms underlying epithelial cell plasticity during development and disease. The project will involve studying how this fundamental property is orchestrated during morphogenesis of the Drosophila midgut, and also in exciting Drosophila cancer models that we have recently generated. This project will combine molecular biology with powerful Drosophila genetics, quantitative image analysis and high-resolution microscopy on our own dedicated multiphoton confocal. It will also involve making targeted Drosophila mutants using CRISPR, and analysing their effects at the subcellular level in fixed and living samples. This is a unique opportunity for you to carry out cutting-edge microscopy, and develop your skills in an exciting multidisciplinary environment.

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: http://www.sheffield.ac.uk/postgraduate/research/apply/applying

*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

Campbell, K. and Casanova, J. (2016). A common framework for EMT and collective cell migration. Development 143, 4291-4300.
Campbell, K. and Casanova, J. (2015). A role for E-cadherin in ensuring cohesive migration of a heterogeneous population of non-epithelial cells. Nat Commun 6, 7998.
Matorell O, Merlos-Suárez A., Campbell K, Barriga F, Christov C, Miguel-Aliaga I, Batlle E, Casanova J. and Andreu Casali A. (2014). Conserved mechanisms of tumorigenesis in the Drosopihla adult midgut. Plos One.
Campbell, K., Whissell, G., Franch-Marro, X., Batlle, E. and Casanova, J. (2011). Specific GATA factors act as conserved inducers of an endodermal-EMT. Dev Cell 21, 1051-1061.