HOME   RESEARCH   PEOPLE   PUBLICATIONS CRYSTAL GALLERY  CONTACT  Molecular Mechanisms of Bacterial Virulence Bacterial pathogens that have extensively co-evolved with their hosts display remarkably sophisticated adaptations, often culminating in intricate biochemical interactions between the microbe and eukaryotic cells. Bacterial virulence factors and toxins are now known to manipulate host processes spanning cytoskeletal assembly to cell cycle progression. Employing techniques from biochemistry, cellular microbiology, and X-ray crystallography, we study the molecular mechanisms of this pathogen-host interaction. Using protein structure as a foundation, our primary focus is on understanding the mechanisms by which bacterial virulence proteins modulate the host. Such studies will provide a framework for an understanding of bacterial pathogenesis at the molecular level and for the design of novel antibacterials. Virulence Factor Delivery into Host Cells Bacterial pathogens achieve the internalization of a multitude of virulence factors into eukaryotic cells. We are studying several such mechanisms, focusing primarily on delivery by the specialized protein type III secretion system of Gram negative bacterial. Pathogenic Modulation of the Eukaryotic Cytoskeleton Learning to understand how bacteria restructure our cells for their benefit. Studies include examination of virulence factors targeting actin, tubulin, and signal transduction pathways impacting cytoskeletal structure. Pathogenic Modulation of the Eukaryotic Cell Cycle Examining the molecular basis for bacterial alterations in cell cycle, both inhibitory and stimulatory. Projects include toxins that damage DNA or act through cell cycle regulatory pathways. Pathogenic Modulation of Eukaryotic Programmed Cell Death Examining the molecular basis for bacterial alterations of host programmed cell death. Projects include factors of both animal and plant pathogens, focusing on the latter which often impair the plant hypersensitive response. Discovery of Virulence Inhibitors We are interested in the possibility of virulence inhibitors serving as therapeutic agents, and are using computational and chemical screening to identify such compounds, leveraging our tools in structural biology.