The Division of Biochemistry is focused broadly on understanding the host-pathogen relationship in molecular terms. With this goal, we address characterization of microbial proteins that are involved in pathogenesis of enteric diseases and host immune response in terms of their solution structure, biochemical and biophysical characteristics and genetic regulation by using the techniques of chromatography, spectrofluorimetry, calorimetry, confocal microscopy and molecular biology.
Highlights of recent work include:
- Demonstration of Vibrio cholerae cytolysin/hemolysin (VCC) as a unique pore-forming toxin (PFT) with specific carbohydrate-binding activity. Interestingly, VCC interacts nonspecifically with synthetic and membrane vesicles by its surface amphipathicity and not through its lectin domain. The lectin domain is recruited by the toxin to interact with non-carbohydrate cytoskeletal proteins to insert into the membrane bilayer.
- Mechanism of unfolding of VCC monomer and refolding to transmembrane oligomeric channel in lipid-water interface of the target membrane.
- Development of a PCR-based identification system of the enterotoxigenic Escherichia coli (ETEC) as an alternative to the existing serological identification scheme.
- Characterization of the Colonization Factor Antigen (CFA) in terms of genetic regulation, subunit composition and domain organization.
- Elucidation of the role of chitinase and chitin-binding proteins of V. cholerae in colonization of the human gut and survival in its ecological niche.