Molecular Virology

My research program is focused on understanding the mechanisms of negative-stand RNA virus transcription and replication. Our model system is the transcription complex of vesicular stomatitis virus (VSV) which contains a large multifunctional protein. We are integrating genetic, biochemical and recombinant DNA technologies to the identification of functional domains within the VSV transcription complex. Specific approaches include: identification of functional and structural mutational lesions in spontaneous mutants; generation of site-directed mutations targeted to conserve regions which we recently identified by direct RNA sequencing; and enzyme active site-directed photoaffinity labeling. Knowledge that emerges from these studies will direct the design of new therapeutic agents for a wide array of human pathogens, and will contribute to our understanding of proteins that contain useful constellations of enzyme activities.