Evolutionary adaptations in the induction and control of acute inflammation

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The evolution of immune defense mechanisms remains the principal interest of my lab. Specifically, we focus on the fundamental contributions of white blood cells to the balance between pro-inflammatory and anti-inflammatory responses following infection. These are critical to antimicrobial defenses and maintenance of tissue integrity. Identification of novel evolutionary adaptations opened new doors to combat pathogens but in some cases also contributed to disease (e.g. autoimmunity, cancer). During the second installment of my NSERC Discovery program (2013-2018) my lab took significant strides towards defining the evolutionary contributions of phagocytes (well-conserved immune cell eaters) to the induction and control of acute inflammation. Development of novel comparative immunology tools for examination of cell function, and side-by-side comparisons of animal models that span large evolutionary distances (mammals, birds, bony fish, agnathans) identified key differences in the mechanisms that promote and control acute inflammation. This research supported the training of 46 highly qualified personnel (3 PDF, 6 PhD, 5 MSc, 26 UG, 1 RA, 5 Tech), whose excellence is reflected in 40 peer-reviewed publications, 69 awards including 1 PDF, 2 Vanier CGS (+1 ongoing nomination), 1 Julie Payette, 2 PGS-D, and 3 CGS-M NSERC Scholarships. Herein, I propose to use a combined molecular and cell biology approach that employs animal models and cell culture techniques to further dissect the evolution of the acute inflammatory response. Specifically, we will focus on two complementary but non-overlapping aims: 1) to dissect the evolving contributions of neutrophils to the transition between pro-inflammatory and resolution states at an infection site, and 2) to define the links between behavioural thermoregulation, immune activation, acute inflammation control, and the establishment of long-term immune memory. 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 and offer new opportunities for the prevention of undesirable autoimmune and chronic inflammatory conditions. In addition, the proposed research has direct applicability to the aquaculture industry in the short-term (field applications expected in vaccination and drug-free health approaches within 5 years) and will help address a four-decade debate on the evolutionary origins of endothermy.