Cells must interface with and adapt to the outside world, and one critical way they achieve this is through the dynamic and specific action of secretion systems that transport molecules in and out of cells. Over the last several decades, scientists have identified numerous cellular secretion systems from bacteria to human. However, there are still many unanswered questions about precisely how and when they function. The goal of our research is to integrate biochemical, biophysical, and genetic approaches to understand the structure, regulation, and function of bacterial secretion systems in their physiological contexts. The results of this approach will shed new light on our understanding of the fundamental process of translocation across membrane, a necessary process for all cells, as well as how we think about bacterial pathogenesis.