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Targeting virus-host cell interactions during negative sense RNA virus infection


Project Description

Viruses can survive and reproduce only in the living cells of a host. To do so they must alter host cell physiology to avoid immune detection and create an environment favourable for viral survival. Negative-sense RNA viruses include many serious fast acting pathogens that remain a threat to human health. Examples include Rabies Virus, Ebola Virus, Influenza A Virus and Respiratory Syncytial Virus. Using global proteomic approaches, work in the Mankouri/Barr laboratories has identified several novel virus-host protein interactions that may govern virus survival across this virus family.

A project is now available to validate the proteomic findings using western blotting, sub-cellular fractionation and immunofluorescence microscopy to determine protein abundance and localization. Validated proteome changes will then be ablated in virus infected cells using RNAi methodologies, dominant negative mutants and small molecule inhibitors. It is hoped these studies will identify new strategies to impede virus survival. The PhD will provide a wide range of cell biology, molecular biology and virological techniques.

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

Research output data provided by the Research Excellence Framework (REF)

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