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- Reader in Virus Cell Biology
- Div of Infection & Immunity
- Faculty of Medical Sciences
UNAIDS estimates around 33 million people are living with HIV/AIDS and approximately 25 million have died. While the ultimate goal remains the development of an effective HIV-1 vaccine, there is also a need for new and improved anti-viral strategies and this requires a better understanding of the molecular cell biology and pathogenesis of HIV-1 infection.
The research interests of my laboratory are broadly aimed at understanding how HIV-1 assembles in and disseminates between CD4 T cells - the main targets for HIV-1 infection in vivo.
Cell-cell spread at Virological Synapses
Previous work by us and others have shown that direct cell-cell spread of HIV-1 between T cells is a very efficient mode of viral dissemination. Cell-cell spread of HIV-1 takes place across a virus-induced multimolecular structure called the virological synapse (VS)(see publications). Our identification of the HIV-1 T cell VS provided a molecular framework to explain how cell-cell spread of HIV-1 occurs and why it so efficient. The VS is characterised by cytoskeleton-driven recruitment of viral proteins, adhesion molecules and entry receptors (CD4 and chemokine receptors) to the site of contact between an HIV-1-infected T cell and a susceptible target T cell. This promotes rapid infection of the target cell by focussing virus assembly and budding to the site of cell-cell contact. Increasing evidence shows that cell-cell confers a number of replicative advantages to the virus, including more efficient spread and may allow HIV-1 to evade aspects of the humoral immune response, innate antiviral restriction factors and antiretroviral drugs. Thus cell-cell spread at VS may pose a considerable barrier to HIV-1 eradication from the host. The VS shares many similarities with a well-described structure called the immunological synapse (IS) and we hypothesise that HIV-1 spread at the VS may involve related cellular machinery, and that HIV-1 hijacks elements of the regulated secretory pathway to transport viral proteins and coordinate assembly and egress. Our current research is focussed on delineating the contribution of T cell trafficking pathways and associated molecules to HIV-1 pathogenesis in T cells. We are also seeking to identify cellular proteins that regulate VS formation and to delineate how they contribute to HIV-1 replication and spread.
The cell biology of HIV-1 replication
Virus assembly is a complex series of well-orchestrated events, in which all components must be delivered to the appropriate cellular location in a temporally and spatially controlled way. We are interested in determining how the viral envelope glycoprotein (Env) and the major structural protein Gag are trafficked to sites of HIV-1 assembly in T cells during both cell-free and cell-cell spread. We are particularly interested in the trafficking of Env and its incorporation into virions because of the essential role Env plays in viral infectivity, tropism and VS formation.
I lecture on the Molecular Virology course and MSc programs.
|2000||PhD||Doctor of Philosophy – Medicine||University of Melbourne|
|1995||BSc Hons||Bachelor of Science (Honours) – Medicine||University of Melbourne|