The focus of our research program is the structure determination of integral membrane proteins by x-ray crystallography and functional analysis of these proteins using biophysical, biochemical, and cell biological techniques. We study transporters embedded in the outer membranes of Gram-negative bacteria, which are surface accessible and therefore have the potential to be good vaccine and/or drug targets against infectious diseases. We also study the membrane-associated, or soluble protein, partners that interact with outer membrane transporters to better understand how these systems function in vivo. Current topics in the lab include (1) small molecule and protein import across the bacterial outer membrane, (2) protein secretion by pathogenic bacteria, and (3) protein import across mitochondrial outer membranes. Our lab currently studies several distinct proteins. Some are common to many different kinds of bacteria and are required for their survival, while others are uniquely involved in the development of E. coli or Yersinia pestis (the bacteria that causes the plague) infections. Recently, we have also started to study mammalian proteins, which may play a role in the progression of neurodegenerative states like Alzheimer’s and Parkinson’s diseases.
Multidrug resistance arising from indiscriminate and widespread use of antibiotics is a growing health threat, and we need to develop much better strategies for treatment and prevention of bacterial infections.