Viral Infection

Bacteriophages are the most abundant biological entity in the biosphere and are responsible for much of bacterial evolution. Most phages utilize elaborate tail machines to eject their genome into a host cell to cause infection. Our studies provide molecular insights into the mechanisms by which tailed phages overcome the multiple barriers of the bacterial cell envelope to deliver their viral DNA and proteins into the host cell cytoplasm. We combine structural biology in situ with genetics and physiology to advance fundamental knowledge of how these highly sophisticated molecular machines infect their bacterial hosts. These studies not only provide insight into the evolution of bacterial pathogenicity but also illuminate basic biological problems, such as molecular host-cell recognition; protein-protein, protein-DNA, and protein-membrane interactions; and penetration of the cell membrane by large macromolecules. Our current research aims to fully elucidate the molecular mechanisms by which the bacteriophage T7 genome ejection machine undergoes massive conformational changes to initiate infection and effect DNA translocation.

This project is supported by NIH/NIGMS.