Dynamic imaging of intracellular signaling pathways during infections of human epithelia

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The research interest of my laboratory is to understand how cells perceive changes in their environment and elaborate an appropriate response to these changes. The coupling of this perception to a response is termed signal transduction, as it involved the transmission of the information perceived by the cell to machineries involved in cellular activities. These signals are transmitted via a wide variety of means and their study is essential to properly understand cell functions. I'm particularly interested in the response generated by a pathogen when it meets a target host cell. Epithelia are tissues that lined our body forming a physical barrier between our inner organs and the surrounding environment. Our entire life as humans is spent in contact with countless microorganisms, and the epithelium plays a key role in protecting us from harmful pathogens. In this proposal we will look at the differences in response of five epithelia (skin, lung, intestine, kidney and cervix) to an opportunistic pathogen, the bacteria Staphylococcus aureus to understand the fundamental mechanisms of signal transduction in the host-pathogen interaction. The nature of these signals will vary according to a number of parameters like strength, duration and amplitude, which are all essential in giving rise to the specificity needed for different cellular activities using a finite number of molecules. The majority of studies in signal transduction are based on end-point assays, from which it is difficult to evaluate the importance of the aforementioned parameters. Therefore we are proposing to develop fluorescent markers of key intracellular pathways to dynamically measure their activation following the exposure of epithelial cells to S. aureus. Taken together we hope to better understand the fundamental mechanisms of perception of an infection by the epithelium initiating the host response.