Understanding the Role of Cellular Chloride Channels in Virus Induced Cancers

Lead Research Organisation: University of Leeds
Department Name: Astbury Centre

Abstract

Background.
Viruses must infect cells in order to multiply. By specifically modifying processes within infected cells, viruses are able to create an environment favorable for their own survival, and more often than not, this occurs at the expense of the host. Understanding how viruses exploit and subvert host cell processes has revealed much about how cells perform crucial biological functions.

Objectives.
We have new and innovative preliminary data showing that Merkel Cell Polyomavirus (MCPyV), the causative agent of Merkel Cell Carcinoma (MCC) an extremely aggressive form of skin cancer, enhances the expression of two intracellular chloride (Cl-) channels. By silencing these channels, MCPyV-induced cell motility and invasiveness are inhibited. This studentship will elucidate why Cl- channels are critical for MCPyV-induced MCC and in doing so, enhance our understanding of the biochemical role of these channels in cellular physiology. We will use this information to validate the efficacy of Cl- channel modulating drugs to prevent MCPyV-induced MCC.

Novelty.
Targeting cellular Cl- channels represents a promising antiviral strategy for the development of MCPyV-induced MCC, as ion channel blocking reagents are an established therapeutic approach for a range of human diseases.

Timeliness.
Our original findings on virus-ion channel interactions have been published in high impact journals such as PNAS and Journal of Virology and the role of cellular ion channels during the lifecycle of other viruses has emerged with papers in PNAS and Science. This proposal therefore advances an important and growing area in which the current applicants are at the leading edge.

Experimental Approach.
This proposal will characterize the cellular roles of the specific Cl- channels induced by MCPyV, identifying previously unknown cellular pathways exploited by viruses, as well as revealing new targets for antiviral therapy.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011151/1 30/09/2015 29/09/2023
1940756 Studentship BB/M011151/1 30/09/2017 31/12/2021 Hayley Pearson