Grant: Doctoral: Vanier Canada Graduate Scholarships

1 in 18 Canadians die from sepsis (the body's response to a severe infection), each year. One of the challenges in treating sepsis is that it is very hard to predict which patients with an infection will need intensive treatment versus which patients will recover uneventfully. My research supervisor's laboratory has recently shown that patients' levels of high density lipoprotein (HDL) cholesterol (the "good cholesterol") drop quickly during sepsis. Importantly, the greater the drop in HDL levels, the greater the chance that a patient will die or suffer from serious organ failure. What is unknown is what controls the drop in HDL during sepsis, and whether genetic variation (differences in the DNA sequences among people) plays a role. My project is aimed at exploring the genetic mechanisms of HDL levels during sepsis. My preliminary data has identified a new gene variant that appears to play a major role in controlling the drop of HDL levels during sepsis. To complete my work, we will examine the DNA of patients with sepsis whose HDL levels drop very low, compared to patients whose HDL levels do not drop as much. Through my supervisor and his collaborators, we have access to large cohorts of patients with sepsis that have been collected from previous studies. We will also examine the function of the gene variants that we identify by introducing these variants into cells and examining the function of the gene products. This work is important for several reasons. Firstly, this work could lead to "personalized medicine" approaches to sepsis, by predicting which specific patients will develop the most dangerous consequences of an infection based on their genetics. Secondly, this project may lead to new ways to treat severe infections by targeted HDL levels. Ultimately this work will lower the burden of death from sepsis and severe infections among Canadians.