I am interested in the structure, function, assembly, and disassembly of viruses and cellular macromolecules. I am particularly interested in using structural techniques to understand virus cell entry (poliovirus) and viral evolution (papovaviruses). My primary research tool is cryoelectron microscopy and three-dimensional reconstruction (cryoEM). I also have an interest in improving cryoEM techniques.

Virus cell entry is a crucial step in the infection of a host cell. During cell entry, animal viruses 1) recognize and attach to a host cell and 2) nucleic acid is delivered to the appropriate site in the cell. Enveloped viruses, such as HIV and influenza virus, have an outer membrane with embedded proteins that facilitate fusion of the viral and cellular membranes. Non-enveloped viruses such as poliovirus do not have a membrane and must breach the cell membrane by a different mechanism. This mechanism is not well understood for any non-enveloped virus. My lab is using poliovirus as a model system to understand cell entry of the non-enveloped viruses.

Poliovirus as viewed via cryoEM. Diameter = 33 nm. Resolution = 2.2 nm. (J. Virol. 74:1342)

Hypothetical model of poliovirus cell entry. The virion (160S) interacts with poliovirus receptor and changes into an intermediate (135S) form. The hypothesis is that the intermediate particle interacts with the membrane, a channel is formed, and then RNA enters the cell.