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Jimmy Feix

Jimmy B. Feix, PhD

Professor

Locations

  • Biophysics
  • MFRC 2040B

Contact Information

Education

Postdoctoral Fellow in Membrane Biophysics, Medical College of Wisconsin, Milwaukee, WI, 1981-1986
PhD, Chemistry, University of Kentucky, Lexington, KY, 1981
BS, Chemistry, Western Kentucky University, Bowling Green, KY, 1976

Biography

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.

Biography_White Box_Filler

Research Interests

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.

 

Mechanisms of Antimicrobial Peptides: Membrane Interactions
Antibiotic resistance is an increasingly serious problem in the treatment of infectious disease. During the past two decades, a large number of peptides with potent antibacterial, antiviral, and antifungal properties have been identified from a wide range of both vertebrate and invertebrate species. These antimicrobial peptides (AMPs) are an important component of the innate arm of host resistance, serving as a first line of defense against infection. Despite being evolutionarily ancient, resistance to AMPs has only rarely been observed. Consequently, there is great interest in the development of these peptides for the treatment of drug-resistant infections.

 

Models of Transmembrane Channel Formation



Our laboratory is involved in elucidating the mechanisms by which AMPs disrupt bacterial membrane structure, determining the basis of AMP selectivity for microbial cells, and developing more effective antimicrobial peptides and peptidomimetics. Whereas classical antibiotics generally target cell wall synthesis, protein translation, or some other highly specific target, AMPs are believed to function by directly disrupting the microbial cell membrane. Peptides are prepared using either recombinant DNA methods or solid-phase chemical synthesis, and their interactions with model membranes (liposomes) and cells are characterized by a variety of physical techniques including circular dichroism, fluorescence, and EPR site-directed spin labeling (SDSL). Our fundamental hypothesis is that a more complete understanding of peptide structure and dynamic interactions with the membrane will allow the design and development of improved AMPs and related antibiotics for the treatment of infections by existing drug-resistant strains such as Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA).

Membrane Proteins I (PDF)

Membrane Proteins II (PDF)

Publications