l am interested in the biology of pathogen-host cell interactions. l believe that the development of novel therapeutic and preventive approaches to infectious diseases depends on the understanding of the determinants that confer a microbe its pathogenic properties. My short term plans are to identify the Salmonella virulence loci with a special emphasis on those required for intramacrophage survival and resistance to antimicrobial peptides. My long term goals are to develop molecular explanations for the mechanisms used by microbes to prosper within host tissues. An RCDA would provide me a unique opportunity to spend almost all my academic time doing research rather than devoting it to teaching or administrative work. To advance to the next level of understanding of the virulence factors being identified in our laboratory will require the use of new technologies in the areas of immunology and cell biology. l believe that an RCDA award would allow me to explore new areas and train myself in immunobiology with collaborators at my institution. I propose experiments to investigate the PhoP/PhoQ regulatory network of Salmonella typhimurium by identifying the targets of PhoP regulation required for virulence and the signal transduction pathway that modulates expression of these determinants. Salmonella is an important health problem both in the US and worldwide and it provides an ideal model for many other pathogens which are not amenable to genetic analysis. A successful accomplishment of our goals will result in the identification of novel genes responsible for Salmonella pathogenesis, a better understanding of the mechanism of resistance to antimicrobial peptides, and will shed light on the mechanisms used by microbes to modulate the immune response and intracellular trafficking.
