Research Interests:

Upon invasion of a host cell, intracellular pathogens must actively ensure their survival in an immediately hostile environment. One such survival tactic of some pathogenic bacteria is through the subversion of host membrane fusion machinery, thereby inhibiting phagolysosomal fusion and subsequent delivery of the bacterium to the host degradative lysosome. The foodborne pathogen, Salmonella enterica, and the causative agent of Legionnaire’s disease, Legionella pneumophila, are examples of such bacterial pathogens that utilize this particular survival tactic. While evading host cell defenses in this manner is key to the organism’s ability to cause infection and disease, the mechanisms underlying these evasion pathways remain poorly understood. Many studies have tentatively identified bacterial factors thought to be important for the disruption of normal host membrane dynamics, but the biochemical analysis of these factors remains lacking. By employing a powerful in vivo and in vitro model system of eukaryotic membrane fusion, my laboratory will investigate the biochemistry of eukaryotic membrane fusion, identify and biochemically characterize bacterial effectors capable of modulating membrane fusion, and finally analyze these activities within the context of pathogenesis.

Vacuoles of the budding yeast Saccharomyces cerevisiae serve the equivalent physiological function of the mammalian lysosome, and undergo constant rounds of fission and homotypic (self) fusion in response to cellular growth conditions. Isolation of these fusogenic organelles from yeast is now a straightforward task, and robust colorimetric assays have been developed to assay the multi-stage process of their fusion in vitro. As an excellent model of general eukaryotic SNARE-, Rab GTPase-, and SM protein-dependent intracellular membrane fusion, the yeast homotypic vacuole fusion system will comprise the backbone of our genetic, molecular, and biochemical approaches. Initial studies in the lab will characterize factors that allow an organism to drive a given membrane fusion event with a specific set of fusion machinery. The recent discovery that a yeast protein complex (the so-called HOPS complex) provides a proofreading activity to ensure proper homotypic vacuole fusion will be further studied. In addition, we will conduct genetic and biochemical screens of the intracellular pathogens Salmonella and Legionella to identify bacterially-produced inhibitors of vacuole fusion in vivo and in vitro. Mechanistic information gleaned from these studies will open new avenues towards the detailed study of basic bacterial pathogenesis.

Congratulations to Jeff Bose, who graduated with a PhD in Microbiology in 2007. He was awarded a National Research Service Award from the NIH for his postdoctoral project with Dr. Ken Bayles at the University of Nebraska Medical Center. The title of the project is "The Molecular Control of Cell Death in Staphylococcus aureus".

Dawn Adin (Ph.D. 2008) earned her B.S. at Jacksonville University in 2001. She then entered the Microbiology Graduate Program and joined Eric Stabb’s laboratory.

Emily DeCrescenzo Henriksen (Ph.D. 2008) obtained her PhD from the Department of Microbiology in 2008 with Dr. Joy Doran-Peterson and is currently working at the Idaho National Laboratory. After completing a two-year postdoctoral position, Emily will transition to a staff scientist position at INL in August 2010. Emily continues to work on biofuels, studying extremophilic enzymes and their applications in bioethanol production.

Kate Brandon (M.S. 2008). After graduating with her Masters in December 2008, Kate Brandon started working at Novozymes, the world's leading enzyme supplier (located outside Raleigh, NC). As an associate scientist in the Enzyme Application R&D department, she has continued to work on enabling the biomass to ethanol industry, research she started in Dr. Joy Doran Peterson's lab. In early 2010, Novozymes launched Cellic CTec 2, the first commerically viable enzyme solution for second generation biofuels, a product she helped to develop and qualify.

Andrea Zbell (Ph.D, 2008) is currently a postdoctoral associate in Dr. Phil Rather’s lab at Emory University (Atlanta, GA), where she has been studying biofilm formation by Acinetobacter baumannii. Indeed Dr. Rather recently presented a seminar to our (UGA) Microbiology Department, and a portion of the presented work was Andrea’s. Andrea is currently writing a manuscript about this work. While conducting the postdoctoral research in Atlanta, Andrea also taught as an adjunct faculty member at Southern Catholic College, in Dawsonville, GA.

Todd Smith (PhD, 2009) After studying the regulation of flagellar genes in Helicobacter pylori with Dr. Tim Hoover, Todd was awarded an American Society for Microbiology Post-doctoral Fellowship in Infectious Disease and Public Health Microbiology. This two-year fellowship must be carried out at one of the Center for Disease Control and Prevention's national laboratories. Todd chose to work at the CDC in Atlanta with Dr. Charles Rupprecht in the Rabies Program as part of the Division of High Consequence Pathogens and Pathology.

Michael Gatlin (Ph.D. 2009) Michael’s dissertation research with Dan Colley was on host immunogenetics in relationship to resistance to reinfection by schistosomes. His work followed up on 40 years of research by Dan on the immunology of schistosomiasis. As fate would have it, Michael’s postdoctoral research in Nancy Manley's lab at UGA on the developmental biology of the thymus was in the same area as Dan’s work 41 years ago, i.e. lymphocyte development in the thymus!

Laura E. Williams (PhD 2009). After finishing her PhD with Dr. Anne Summers, Laura started her postdoctoral research in the laboratory of Jennifer Wernegreen's Laboratory (originally located at the Marine Biological Laboratory in Woods Hole, Mass., but since moved to the Institute for Genome Sciences and Policy, Duke University, Durham, N.C.). Her research focuses on genome evolution in Blochmannia, which are bacterial endosymbionts of carpenter ants.