Major Field of Interest
B.S. Washington University in St. Louis (1983)
Ph.D. University of California-Davis (1989)
Institut de Biologie Physico-Chimique, Paris (1989-1991)
University of Connecticut Health Center (1991-1996)
Bacillus subtilis Projects
Polymerization of the bacterial peptidoglycan cell wall has proven to be one of the best targets for antibiotics because it is essential for the cells, is highly conserved across essentially all bacterial genera, and takes place outside of the cell, where the antibiotics have easy access. A greater understanding of the details of peptidoglycan polymerization will contribute to the development of new antibiotics. With funding from a grant from the NIH, we study many aspects of peptidoglycan synthesis in B. subtilis. These include: 1) The roles played by the 16 different penicillin-binding proteins (PBPs) in putting together vegetative cell walls and spore cell walls of the proper shape, size and structure; 2) The protein-protein interactions made by the major PBPs; 3) Regulation of the timing of spore peptidoglycan synthesis; and 4) The relationship of spore peptidoglycan structure and spore resistance properties.
Bacillus anthracis Projects
The spores that cause Anthrax can lie in a dormant, extremely stable state for many years. In addition, these spores are highly resistant to most treatments commonly used for disinfection. Once the spores enter a host body, they must germinate and return to a growing state in order to cause disease. This germination also renders the spores sensitive to disinfection agents. With funding from a grant from the NIH, we are determining the enzymatic activities required for degradation of the B. anthracis spore peptidoglycan wall, an essential step in spore germination. With an understanding of the proteins involved in germination and the mechanism that triggers this process, we may be able to design ways to either prevent or stimulate germination. This can lead to better methods of infection control and cleanup of contaminated sites.
Clostridium difficile Project
The bacterium C. difficile has become one of the most serious human bacterial pathogens in the United States, especially among hospitalized patients that have undergone aggressive antibiotic treatment for a prior condition. C. difficile's ability to produce a heat-resistant endospore is the most important factor in allowing it to spread between patients, to persist in clinical settings, and to cause frequent relapses in patients. With funding from the NIH, and in collaboration with Drs. Rich Helm, Rick Jensen, and Stephen Melville, and the VT Mass Spectrometry Incubator, we will identify proteins within the inner membrane of C. difficile spores, with the goal of better understanding the spore germination process. With this information, we may be able to design ways to either prevent or stimulate germination. This can lead to better methods of infection control and cleanup of contaminated sites.