The majority of research in the group focuses on various aspects of HIV evolution.  A number of research themes are currently being investigated:

 

HIV coreceptor usage

One of our primary research goals is to understand the underlying molecular mechanisms enabling HIV to change from using CCR5 to CXCR4 for host cell entry.  Such understanding is vital in order to fully understand the potential for resistance to CCR5-antagonists therapeutic approaches.  We are particularly interested in comparative analysis between HIV-1 subtype B and C to understand why it appears that subtype C tends to change to use CXCR4 far less frequently than subtype B.

 

HIV Molecular Epidemiology and Dynamics.

The group is part of a large collaboration studying many aspect of molecular evolution of HIV in Karonga District, Malawi.  Research involvement in this collaboration includes characterising HIV diversity present within Karonga District, studying the prevalence and emergence of drug resistance to various antiretroviral therapies (ARTs), examining the viral factors responsible for long term survival in individuals and characterising the extent of CXCR4-usage in subtype C infected individuals.

Using sequence data from both the Karonga Prevention Study cohort and other cohorts we are using various approaches to understand the prevalence and significance of sexual networks in the transmission of HIV.    

 

N-linked glycosylation in HIV.

As part of the post-translational processing of a HIV virion carbohydrates are added to the surface of the virion by the hosts glycosylation mechanism.  The binding of such N-linked glycans conveys protection to a virions surface proteins by acting as a shield to avoid detection by the host's immune system.  These carbohydrates, however, may comprise a novel target for HIV therapeutics and we are currently studying the three-dimensional properties of this 'glycan shield' to further understand it's therapeutic potential. 

 

Ultra-deep sequencing.

The advent of next generation sequencing technologies means that we can theoretically study the entire spectrum of viral variants circulating within a HIV infected individual.  Such approaches means we can now answer many questions about within host viral evolution however managing and analysing such large volumes of data means comes with significant challenges.

As well as using ultra-deep sequence data generated using Roche's 454 approach to answer specific questions we are also developing computational approaches to manage and explore ultra-deep sequence data.