Our lab researches intracellular membrane trafficking and calcium-regulated exocytosis in eukaryotic cells. Diseases such as diabetes, mood disorders, viral infections, and cancer are all linked to a defect in the way that cells secrete small particles enclosed in sac-like containers, called granules. For instance, cells in our immune system, like white blood cells, release granule contents which hunt down and destroy cancerous or infected cells. With the Pew award, I aim to identify the protein machinery cytotoxic T lymphocytes (CTLs) use to secrete granules that break down cells. Using simulated emission depletion microscopy, we will analyze the spacio-temporal distribution of the proteins underlying lytic granule secretion. Additionally, we will test the role of individual components regulating exocytosis with reconstituted functional assays, and create two new fusion assays specifically tailored to immune secretion. This work will have far-reaching relevance beyond cell-mediated killing, as similar mechanisms likely account for release of hormones in the pancreas and in other organs, underlying significant health problems like diabetes.