Angela Wilks, PhD

The focus of my research has been the relationship of structure to function in heme proteins. An area of particular interest at the present time is the acquisition and utilization of heme by bacterial pathogens such as Shigella dysenteriae , Vibrio cholerae and Corynebacterium diphtheriae . Iron is essential for the survival of all bacteria and many pathogenic bacteria have developed sophisticated mechanisms by which they utilize the hosts heme containing proteins as a source of iron. The ability of pathogenic bacteria to acquire iron is in part linked to their virulence. The goal of the project is to identify and characterize critical proteins involved in the acquisition and utilization of heme. Understanding the mechanism of heme uptake and iron release at the molecular level will allow rational design of therapeutic agents for the treatment of bacterial infections.

The recent cloning of genes for the outer-membrane receptor (Shu A) and a heme binding protein (Shu S) from S. dysenteriae will allow characterization of the heme transport proteins. In addition the recent identification and expression of the heme oxygenases from C. diphtheriae , N. meningitides , and P. aeruginosa will allow the mechanism of iron release to be investigated. Site-directed mutagenesis together with physical techniques such as optical absorption, resonance Raman and NMR will be used to determine the structural features required for heme binding and catalysis.