Grant: CIHR Clinician Scientist - Phase 1

Many infectious diseases are caused when harmful bacteria successfully invade human cells. Bacteria have evolved mechanisms to disrupt the host cell's structural framework or cytoskeleton, allowing them entry into the host cell; this is seen during food-borne infections caused by Salmonella and E. coli, as well as periodontal (gum) diseases. The purpose of this grant application is to study the mechanisms and to identify the proteins that are responsible for maintaining the health and viability of human cells exposed to harmful bacteria. The current project will focus on two major questions. First, we will identify the molecular signals that operate during bacterial infection of cells and learn how these signals affect cell-microbe interactions. In addition, a protein known as IQGAP1 is important for many cellular functions and has a role in the control of host cell structure at the cell-bacteria interface. We will therefore test the hypothesis that IQGAP1 in human cells is a key component of bacterial invasion. An improved understanding of how microbes usurp the host cell to effect entry is likely to have important implications for the rational treatment of infectious diseases.