Grant: Research Tools and Instruments - Category 1 (<$150,000)

The immune system constantly monitors the mammalian body against all sorts of danger signals, arising from within the body or from outside. The intrinsic danger signals include apoptotic and dead cells that need to be cleared, abnormal accumulation of metabolites (e.g. gout crystals), and emergence of neoplastic cells. The outside danger signals include physical injury and microbial infections. The immune system responds to these insults at two levels. Most cells of the innate immune system (neutrophils, macrophages, mast cells, natural killer cells, etc) provide the first line of defense with no specificity or memory, while certain others (dendritic cells, macrophages) additionally help to initiate the adoptive immune response. The latter mediated by lymphocytes, provide antigen-specific responses that leave behind a memory to efficiently deal with future encounters. While great advances have been made in understanding the functions of the innate and adoptive immune systems, many aspects remain less clearly understood. As core members of the Immunology graduate program at Université de Sherbrooke, the applicants are studying the nature of help provided by innate immune cells to T lymphocytes of the adaptive immune system (S. Ilangumaran), mechanisms underlying the long-term survival of naive T lymphocytes (S. Ramanathan), signaling via lipid mediators (J-L. Parent), cell death mechanisms including autophagy (D. Gris) and nuclear signaling (P. McDonald). All these research projects, involving many graduate students and postdoctoral fellows, require enrichment or isolation of subcellular fractions. Because the analytical ultracentrifuge that we possess has only limited sample capacity and is insufficient to obtain enough material for detailed biochemical analysis, we request NSERC funding to acquire a preparative ultracentrifuge as a common facility of the Immunology graduate program at Université de Sherbrooke.