Type III Secretion System, Salmonella Secreted Effector Proteins
1992-1996- Aled M Edwards lab, McMaster University, Hamilton, Ontario, Canada–Purification, characterization and crystallization of DNA binding proteins
1996-1998- Roderick Mackinnon lab, Rockefeller University, New York, NY-Purification, characterization and crystallization of a bacterial potassium channel.
1998-2004- Natalie Strynadka lab, University of British Columbia, Vancouver, BC Canada-Purification, characterization and crystallization of various proteins involved in bacterial pathogenesis.
Current Research Summary:
The type III secretion system is central to the pathogenesis of many infectious gram negative bacteria. This complex is composed of oligomeric rings of protein subunits embedded in the inner membrane, outer membrane and periplasm of the bacterium. The “needle complex” has an extension beyond the surface of the bacterium resulting in a syringe like assembly that can transfer protein effectors from the cytoplasm of the bacterium directly to the cytoplasm of the host cell.
In collaboration with the Goodlett lab and Baker lab at the UW and the Strynadka lab at the University of British Columbia, we have mapped detailed, high resolution protein-protein interactions within the base of the type III secretion “needle complex” using a combination of chemical cross linking, mass spectrometry, protein crystallography, and molecular modeling. . We have made significant advances in working out the details of how this important organelle is assembled. In addition to the work on the needle complex structure, various aspects of effector protein structure and function are being studied as well.