Herpesvirus-host cell interactions

Description of projects available to graduate students:
Mechanisms of transcription activation by viral regulatory proteins. The major regulatory protein modulating the expression of all 80 HSV genes is ICP4. This protein is both an activator and repressor of transcription at the core promoter. Numerous studies from our lab have shown that it functions with the basal transcription machinery of the cell. We have generated methods to purify ICP4 and specific ICP4 mutant proteins from infected cells and add them to a purified in vitro transcription system. We have also generated several methods to view interactions at the core promoter. Therefore, this project sets out to elucidate the precise molecular mechanism by which ICP4 affects transcription. This project involves reconstituted in vitro transcription with purified cellular transcription factors and viral regulatory proteins. It also involves protein biochemistry, protein-protein and protein-DNA interaction studies.

Genetics of viral regulatory proteins. This involves engineering specific mutations into the genes for viral regulatory proteins, putting the mutated genes back into herpes simplex virus, and determining the effects of the mutations on the transcription of the remainder of the viral genome and viral growth in culture, and/or in the mouse of herpetic disease and latency.

Mechanisms of repression and activation of latent or persistent viral genomes. These are latency studies that can be conducted in tissue culture and in animal models. We are interested in the viral and cellular factors that influence the chromatin state or packing of persistent viral genomes in ways that promote latency, or reactivation from latency. This project can involve protein biochemistry, virus genetics, molecular biology, cell culture, and animal studies.

Techniques graduate student will learn:
TBA