The goal of our team is to understand the molecular mechanisms of protein transport and organelle biogenesis using Gram-negative bacteria such as Escherichia coli and Klebsiella as model organisms. We are focusing on basic mechanisms of protein transport via the Type 2 secretion system and assembly of surface filaments called Type 4 pili. Both of these complex nanomachines share similar protein components and assemble flexible filaments from membrane protein subunits. In Type 2 secretion system, these filaments (pseudopili) promote secretion of fully folded proteins from the intermembrane space – the periplasm across the bacterial outer membrane. Type 4 pili in Enterohemorhagic Escherichia coli (EHEC) are implicated in bacterial adhesion to surfaces, DNA uptake and natural competence.
We integrate genetic, biochemical and functional analyses with structural, biophysical and modeling approaches to reach detailed mechanistic view of these dynamic macromolecular systems spanning the bacterial envelope. Mechanistic studies of these systems lead to more basic questions in protein science, touching upon protein-protein and protein-membrane interactions, protein folding, localization, quality control and turnover.