Elucidating in vivo functions of hydrogen peroxide

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Essential to an organism's survival is its ability to restore and maintain tissue integrity following injury. One of the earliest and most crucial responses to injury is the production of the oxidant hydrogen peroxide (H2O2). It is often the case that free radicals and oxidants, such as H2O2, are harmful and toxic; however, under certain circumstances, such as injury, cells in our bodies generate oxidants for beneficial purposes, for example to repair damage and heal. Using genetic and biochemical approaches, the central objective of this research proposal is to uncover how H2O2 helps to restore tissue integrity upon injury and damage. Our first aim is to determine what triggers the generation of H2O2 upon injury. Cells have special type of enzymes they use to generate H2O2 in response to injury; however, how they know when to activate these enzymes remains unknown. Using powerful genetic approaches in the model organism, the fruit fly, we will determine how cells turn on this enzyme during injury. Our second aim is to understand how, once produced, H2O2 helps to restore and repair injury. A main proposed function for injury-induced H2O2 is to alert immune cells that injury has occurred and to attract them to the site of injury. Once at the site of injury, immune cells are essential to stave off infection and repair damage. How H2O2 alerts and attracts immune cells remains unknown. Using both genetic and biochemical approaches we will elucidate this critical and essential function of H2O2 in injury repair. Our research will beneficially impact Canadians in numerous ways, including by training highly qualified personnel, by developing Canada's research capacity, and through scientific knowledge advancement. This research program will elevate Canada as a hub for research innovation and excellence in the basic biomedical sciences and redox biology. In doing so it will stimulate economic and societal growth through the training and recruitment of world-class scientists.