Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

During bacterial infection, white blood cells known as neutrophils mount a complex defense response to eliminate the infecting organisms. In healthy individuals, after the clearance of bacteria, neutrophils can terminate this response by undergoing a process of controlled cell death called apoptosis. Failure to undergo apoptosis can result in bystander injury to healthy tissues, a condition known sepsis, defined as a life-threatening organ dysfunction resulting from a dysregulated response to infection. Sepsis is the leading cause of death and disability for patients in an intensive care unit. No specific therapies are available to treat sepsis and management remains largely supportive. One quarter of patients who develop sepsis die; survivors experience a reduced quality of life, and a higher risk of death. In this research program, I seek to understand how changes in neutrophil responses to bacterial signals during sepsis can inhibit apoptosis, and prevent the normal resolution of inflammation. Hence, this study will investigate: 1) How certain proteins within neutrophils can direct cell responses to either cell survival or death. 2) How the formation of certain protein clusters can influence bacterial recognition and cellular responses by the neutrophil. 3) Whether pharmacologic manipulation of these proteins can accelerate bacterial clearance and reduce inflammation in pre-clinical animal models. Our translational studies will use patient blood samples to identify potential new strategies to accelerate the resolution of neutrophil-mediated tissue injury during sepsis.