Jimmy B. Feix, PhD

I received my BS in chemistry from Western Kentucky University and PhD in chemistry from University of Kentucky. I completed my postdoctoral training in membrane biophysics at MCW. I was appointed as MCW faculty in 1985.

My current research interests are in the use of advanced electron paramagnetic resonance (EPR) spin labeling techniques to study the mechanisms that drive peptide – membrane and protein – membrane interactions, and in the development of new peptide antibiotics.

We utilize site-directed spin labeling (SDSL) EPR spectroscopy and other biophysical and biochemical techniques to work on problems related to the membrane interactions of peptides and proteins and the structure and dynamics of membrane proteins.

Mechanism of Activation and Membrane Interactions of Pseudomonas toxin ExoU
ExoU is a 74 kDa protein produced by the Gram-negative bacterial pathogen, Pseudomonas aeruginosa. ExoU is injected directly into eukaryotic cells by a needle-like Type III secretion system (T3SS). Once inside the eukaryotic cell, ExoU functions as a phospholipase to disrupt membranes and facilitate dissemination of the bacterial infection. ExoU also serves as a model system for the study of protein–membrane and protein–protein interactions. In a novel regulatory mechanism, ExoU is activated through protein–protein interaction with ubiquitin (Ub). Since Ub is exclusively a eukaryotic protein, this prevents the ExoU toxin from being activated within the bacterium. Using a combination of site-directed spin labeling EPR and double electron-electron resonance (DEER) spectroscopy, supported by mutagenesis and biochemical studies, we have identified the ExoU–Ub binding interface. Additional EPR studies in conjunction with computational analysis have led to a model for the membrane-bound ExoU-Ub complex. The goals of these studies are to facilitate the development of novel inhibitors of ExoU as a means to attenuate the virulence of P. aeruginosa infections.