Comparative biology of phagocyte antimicrobial responses

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My laboratory is interested in the evolution of white blood cell immune defense mechanisms. Specifically, we focus on the balance between pro-inflammatory and homeostatic responses at an infection site because of its relevance to host immunocompetence and disease prevention. Characterization of well-conserved pathways offers important evolutionary context for generation of the complex immune networks that now exist in higher vertebrates. Moreover, characterization of more recently developed features may help identify vulnerability gaps for pathogen infiltration, or which contribute to unwanted immune reactions (e.g. autoimmunity). During the first installment of my NSERC Discovery program (2008-2012) my lab took significant strides towards the establishment of unique analytical protocols for functional characterization of cellular antimicrobial responses. Side-by-side comparisons of animal models that span large evolutionary distances required that we established transferable tools that help overcome a continued lag in reagent availability (e.g antibody markers). We have begun to make significant contributions to the field, as evidenced by recent publications in Dev Comp Immunol, PLoS ONE and J Leuk Biol (cover article). Herein, I propose to use a combined molecular and cell biology approach that employs animal models and cell culture techniques to further dissect the evolving roles of phagocytes in the control of inflammation. Specifically, we will focus on two aims: 1) to examine the evolution and contributions of neutrophil phagocytosis to the control of inflammation, and 2)to define the role a novel soluble form of the CSF-1 receptor as an effective regulator of inflammation across evolution. All major techniques, infrastructure, and a strong core of trainees are already in place in my lab, and are further supported through university facilities and collaborators. Our results have positive implications for the fundamental understanding of inflammation, may open new doors for the prevention of undesirable autoimmune or chronic inflammatory conditions, and offer novel opportunities for the control of fish diseases in commercial aquaculture systems.