Research

We use biophysical techniques to investigate virus architecture,  assembly  and replication. A particular emphasis is placed on understanding the molecular  interactions that are involved (protein-protein, protein-RNA, and protein-lipid). Our work is carried out in vitro, using purified viral and cellular components.  A variety of biophysical techniques are employed, including spectroscopy, light scattering, micro-calorimetry, X-ray crystallography, and electron microscopy. While the viruses under study have disparate life cycles, they all possess RNA genomes, and they are all enveloped (i.e. wrapped in a membrane that is derived from the host cell). 


Replication machinery of measles and mumps viruses.


Measles and mumps viruses are both members of the paramyxovirus family, and share a similar organization and mode of replication. Within the virion, the nucleocapsid protein packages their genomic RNA into a filamentous complex, termed the nucleocapsid. In the cytoplasm of an infected cell the viral RNA polymerase uses the nucleocapsid as the template for both transcription and genome replication. We are studying the organization of the viral polymerase, a large and complicated molecular machine. We are particularly interested in the way the polymerase engages and moves along the nucleocapsid during RNA synthesis.


Assembly and organization of Rous sarcoma virus.


Rous sarcoma virus (RSV) is an avian retrovirus, closely related to human immunodeficiency virus (HIV). Retroviruses cause cancer and immune disorders in many species. In all such viruses, the Gag polyprotein directs formation and release of spherical virus particles. Subsequently, the polyprotein is cleaved by the viral protease, releasing the structural proteins found in the infectious retrovirus. This results in a structural rearrangement of the virion interior that is essential for infectivity. 

We are investigating the role of the Gag polyprotein, and its constituent domains, in retroviral assembly. We want to identify Gag polyprotein assembly intermediates critical to the formation of spherical virus particles, and to understand the organization of the mature retroviral core, the large assemblage that incorporates the genomic RNA and the replicative enzymes in the infectious virion. 


Applications from people wishing to undertake postgraduate training are welcome. Those having a strong background in the physical sciences, but without experience in biology, are encouraged to apply. Current employment opportunites are listed here.