 Every day, your immune system comes into contact with a number of potentially disease-causing pathogens and it is the job of your cytotoxic T lymphocytes or CTLs to find and kill the cells in your body that become infected with viruses. Now CTLs find virally infected cells when their T cell receptor sees viral protein on the surface of a cell. Engagement of the T cell receptor by viral protein initiates a signaling cascade which eventually leads to the secretion of specialized proteins housed in structures called lytic granules which are able to induce death and kill a target cell. Now because of the importance of CTLs in combating viral infections, it is perhaps not surprising that mutations in genes that affect the development or the overall function of a CTL can lead to severely impaired immune responses and particularly immune responses to viral infections. So one such primary immunodeficiency as we call the subset of diseases is caused by mutations in a protein kinase downstream of T cell receptor signaling called ITK. Now patients with mutations in ITK experience severe immune dysregulation when they become infected with everyday common viruses that in you or I as healthy individuals are dealt with rapidly and efficiently by our fully functioning CTLs. But like many primary immunodeficiencies, the cellular and molecular mechanisms behind this particular sensitivity to viral infections is not well understood. So using a mouse model of immunodeficiency, we find that the loss of ITK leads to reductions in the ability of CTLs to kill virally infected target cells as is shown in the y-axis in the figure to my left. And that these reductions in killing are associated with defects in secretion, that all important final step that I just described earlier, the release of those specialized proteins from lytic granules that induce death in target cells. So given this data, the goal of my research is therefore to better understand the role of ITK and T cell receptor signaling in regulating secretion and killing in CTLs, but also more broadly the development of lymphoproliferative disorders in human beings. So one way we can study secretion in the lab is using TERF microscopy, which is a technique that's uniquely suited for looking at events that occur at the plasma membrane and cells. So in this movie of a CTL, you will see actin, the cytoskeletal structure labeled in red. It accumulates and then forms a ring. And the formation of this ring helps bring lytic granules, which you see in green, towards the membrane, where they then fuse, which you see as that burst of green, to release their contents that are able to induce death in target cells. So once again, we see the accumulation of actin, the formation of a ring, the appearance of lytic granules, and then that burst of green, those fusion events that allow us to visualize secretion in CTLs. So experiments that combine mouse models of immunodeficiency with techniques such as TERF microscopy have provided us with clues to novel roles for ITK and T cell receptor signaling in regulating secretion and killing in CTLs. But have also helped us better understand the defects which may account for the particular susceptibility to viral infections that we see in immunodeficient patients with mutations in T cell receptor signaling components.