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Understanding the Role of Cellular Chloride Channels in Virus Induced Cancers

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  • Full or part time
    Dr Mankouri
    Prof Whitehouse
    Dr Lippiat
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Viruses must infect cells in order to multiply, and consequently they have evolved to modify the cellular environment to favor their own reproduction at the expense of the host. Our recent work has shown that both RNA and DNA viruses manipulate cellular ion channels to exert control over important host cell functions, which then influences their life cycles. Ion channels regulate ion homeostasis across cell membranes and are key players in a broad range of processes including the cell cycle, gene expression, cell signaling and innate immunity.
We have recently identified that Merkel Cell Polyomavirus (MCPyV) induced tumourigenesis and metastatic spread is dependent on the enhanced expression of two intracellular chloride (Cl-) channels. In this proposal, we seek to build upon our compelling preliminary data to investigate and characterize why the deregulated expression of Cl- channels contributes to skin cancer development. As part of this proposal, we will aim to identify new compounds that target the MCPyV- induced Cl- channels. By identifying specific Cl- channel modulators that can impede MCPyV-induced tumorigenesis and metastatic spread, we will open up a new and exciting class of anti MCPyV-induced skin cancer therapeutics.

Funding Notes

BBSRC White Rose Mechanistic Biology DTP 4 year studentship.
Studentships covers UK/EU fees and stipend (c.£14,296) for 4 years to start in Oct 2017. Applicants should have/be expecting at least a 2.1 Hons. degree in a relevant subject. EU candidates require 3 years of UK residency in order to receive full studentship.
Not all projects advertised will be funded; the DTP will appoint a limited number of candidates via a competitive process and the projects selected by the successful candidates will be funded.
There are 2 stages to the application process. Please see our website for more information: http://www.fbs.leeds.ac.uk/postgraduate/phdopportunities.php

References

1. Igloi Z, Patrick Mohl B, Lippiat JD, Harris M, Mankouri J*. Requirement for Chloride Channel Function during the Hepatitis C Virus Lifecycle. J.Virol. 2015. In Press.
2. Mankouri J, Tedbury PR, Gretton S, Hughes ME, Griffin SD, Dallas ML, Green KA, Hardie DG, Peers C, Harris M. Enhanced hepatitis C virus genome replication and lipid accumulation mediated by inhibition of AMP-activated protein kinase. Proc Natl Acad Sci U S A. 2010 107:11549-54
3. Mankouri J, Dallas ML, Hughes ME, Griffin SD, Macdonald A, Peers C, Harris M. Suppression of a pro-apoptotic K+ channel as a mechanism for hepatitis C virus persistence. Proc Natl Acad Sci U S A. 2009 15:15903-8.

How good is research at University of Leeds in Biological Sciences?

FTE Category A staff submitted: 60.90

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