Two major tools in our investigations are aptamer  and human embryonic stem cell technology.

HIV research

AIDS, which is caused by infection with the retrovirus, HIV, currently kills approximately 3 million people and infects an additional 5 million world-wide every year (see UN AIDS for updates). We have been interested in investigating the molecular cell biology of this virus for two decades, principally focussing on the mechanisms of virus entry into cells and RNA-based methods for inhibiting HIV replication.

We have recently isolated aptamers (see below) that bind to the envelope glycoprotein of HIV (refs 1-4, to the right). The ligands turn out to inhibit the infection of lymphocytes by clinical strains of virus from around the world to an extent that makes them very interesting both for clinical applications (such as prevention and treatment) and as reagents for analysing virus-cell interactions.

 Prions

Transmissible spongiform encephalopathies (TSEs), including scrapie, BSE and variant CJD, are associated with the the deposition of an abnormally folded version of the cellular PrP protein in amyloid plaques in the brain. This mis-folded protein may itelf be the infectious agent - a prion - but we structural basis for the process is obscure. We are using the aptamer approach to investigate the problem

Arboviruses

Arthropod-borne viruses are an important source of morbidity and mortality, especially in the developing world. We have had a long-standing interest in investigating the molecualr biology of Flaviviruses, such as Dengue virus, and Bunyaviruses.

Aptamers 

Aptamers are artificial  nucleic acid ligands that are isolated from complex libraries of synthetic oligos. They can be used, like antibodies, to investigate biological systems but are small, protease resistant and do not suffer from the limitations of tolerance, antigen processing and so on.

The principal HIV-susceptible cells in vivo, macrophages and T helper cells, are refractory to genetic manipulation, and are genetically and physiological heterogeneous, from experiment to experiment. To provide a tractable experimental platfrom for HIV studies in pathologically relevant cells, we have developed procedures for differentiating human ES cells in vitro.