MRC National Institute for Medical Research, London
Science for Health
This project is now closed
Understanding early events in retroviral replication
Project supervisor: Kate Bishop (Virology)
Retroviruses cause severe diseases including AIDS and cancer. Many anti-retroviral dugs and cellular anti-viral factors target the early stages of the viral life cycle. However, numerous events that occur during these stages are still poorly understood. Work in our laboratory aims to characterise the molecular events that occur once a retrovirus has entered a cell in order to fully understand retroviral replication and provide potential ways in which to manipulate these processes for the benefit of human health.
The p12 protein of a model retrovirus, murine leukaemia virus (MLV), is essential for the early stages of replication (Yuan et al, 1999), although its precise role is unknown. The key aim of this studentship is to understand the function of p12 and how it contributes to early post-entry events during infection. Using p12 mutants, we have mapped two functional domains in p12 that act sequentially in the viral life cycle, and have proposed a model for p12 function (Wight et al, 2012). In this project, we will further analyse the replication of viral mutants and use a variety of biochemical and virological techniques to define the mechanism of p12 function in different gammaretroviruses. In addition, we will identify p12-interacting factors (both viral and cellular) and use fluorescent microscopy to visualise p12 localisation during viral replication. We aim to compare fluorescent and electron microscopy and develop methods to watch infection in real-time. We expect these studies to expand into a wider investigation of the processes that occur early in the retroviral life cycle.
The project will provide diverse training in a wide range of techniques including virology, molecular biology, biochemistry, cell biology and microscopy.
References
- Yuan, B; Li, X and Goff, SP (1999)
Mutations altering the Moloney murine leukemia virus p12 Gag protein affect virion production and early events of the virus life cycle.
EMBO Journal 18, 4700-4710 PubMed abstract - Wight, DJ; Boucherit, VC; Nader, M; Allen, DJ; Taylor, IA and Bishop, KN (2012)
The Gammaretroviral p12 protein has multiple domains that function during the early stages of replication.
Retrovirology 9, 83 PubMed abstract
See also
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