The objective of the research in my laboratory is to elucidate the pathogenic mechanisms of Salmonella species. One important pathogenic attribute of Salmonella species is their ability to enter mammalian cells. The ability of these bacteria to invade host cells is controlled by a variety of environmental signals that control invasion gene expression. We have performed a variety of genetic screens to identify genes that control the expression of the Salmonella invasion machinery. Those experiments have revealed that the regulatory pathways use two-component signaling systems, known small DNA-binding proteins, and Salmonella-specific proteins. A variety of research projects are underway to characterize these pathways in detail and to explore how regulation of this particular virulence property is integrated into the control of the entire pathogenic strategy of the organism as well as to discover how virulence gene expression is managed within the context of bacterial physiology. This work as provided significant insights into the bacterial-host cell interactions that allow these bacteria to survive and grow within the lymphatic system of mammalian hosts. A second project in the laboratory, which has been recently funded, is a characterization of the virulence factors of Francisella tularensis. This potential bioweapon is a significant pathogen which causes a systemic infection similar to the \"plague\" caused by Yersinia pestis. Work is being initiated to characterize the adherence, invasive, and intracellular survival properties of this organism as well as to develop genetic tools for manipulation and study of the bacteria.