Prof Andrew Fry, Prof K Brown
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
Lung cancer is the leading cause of cancer-related mortality worldwide. Approximately 5% of patients express the EML4-ALK oncogenic fusion that joins the EML4 microtubule-associated protein to the tyrosine kinase domain of ALK. The majority of EML4-ALK lung cancer patients respond remarkably well to catalytic inhibitors of ALK. However, mutations in the catalytic site confer resistance and not all EML4-ALK patients respond with similar efficacy. Hence, new treatments are required.
Interestingly, alternative breakpoints create different EML4-ALK variants that have markedly different clinical outcomes and therapeutic responses. In a major recent discovery, we found that those EML4-ALK variants that bind microtubules (e.g. v3) induce a dramatic change in cell morphology and increase cell migration. Excitingly, this is consistent with EML4-ALK v3 conferring accelerated metastatic spread and worse overall patient survival.
This project will use cutting-edge molecular and cell biology techniques to test the hypothesis that members of the Rho GTPase family coordinate altered dynamics in the microtubule and actin cytoskeleton and that these underlies the observed changes in cell morphology and migration. The outcomes of this project will be a new mechanistic understanding of how EML4-ALK v3 alters cell polarity and migration, and identification of new therapeutic options for lung cancer patients.
Interviews will be held in the week commencing the 11th February 2019.
Entry requirements
Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject. The University of Leicester English language requirements apply where applicable.
How to apply
Please apply via: https://more.bham.ac.uk/mrc-impact/phd-opportunities/
Project / Funding Enquiries
Professor Andrew Fry
[Email Address Removed]
+44 116 229 7069
Application enquiries to [Email Address Removed]
Closing date for applications 20th January 2019
Funding Notes
MRC IMPACT DTP
References
Fry et al. (2016) EML proteins in microtubule regulation and human disease. Biochemical Society Transactions 44, 1281-1288.
Bayliss et al. (2016) Molecular mechanisms that underpin EML4-ALK driven cancers and their response to targeted drugs. Cell and Molecular Life Sciences 73, 1209-1224.
Christopoulos et al. (2018) EML4-ALK fusion variant V3 is a high-risk feature conferring accelerated metastatic spread, early treatment failure and worse overall survival in ALK(+) non-small cell lung cancer. International Journal of Cancer 142, 2589-2598.
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