The Molineux lab studies mechanisms of phage infection and genome ejection in vivo; phage evolutionary genetics and applications of phage. A major research interest is understanding how nucleic acids pass through lipid bilayers. Our model system is bacteriophage T7, which uses three different motor proteins to transport its DNA into the cell at the initiation of infection. The phage ejects proteins into the cell that make a channel for DNA transport across the cell envelope and constitute the first molecular motor. We are characterizing this channel and motor with the aim of reconstructing a DNA translocation system in vitro. The second and third motors are RNA polymerases that transport the T7 genome into the cell by transcription. We collaborate with structural biologists who use electron cryo-tomography to obtain extremely high resolution structures of intermediates of different phages during infection.
Other interests include various host-parasite interactions; currently we are determining the molecular basis for exclusion of T7 by cells containing the F plasmid, evaluating phages for use in phage therapy protocols, using phages as models in evolutionary genetics, and phage genomics. A more specific project underway is to determine the mechanism by which transcription of the T7 genome is switched from catalysis by E. coli to the phage RNAP. Two T7 proteins: gp0.7 and gp2, are involved; in their absence the phage undergoes an abortive infection where the phage genome is degraded. We are analyzing rare mutants that bypass the requirement for these proteins, anticipating that we will uncover a novel regulatory genetic network for phage development.
Fields of Interest
- Molecular Biology and Genetics
- Microbiology, Immunology and Infectious Disease
Centers and Institutes
- John Ring LaMontagne Center for Infectious Disease