Grant: Discovery Grants Program - Individual

My NSERC research program is focused on the immunogenetics of the wild duck population and its influence on their role as host of influenza. We know that 15-30% of wild ducks are infected with influenza in Canadian lakes at any time. We would like to know how ducks clear the virus, and be able to correlate the genetics of ducks with their disease susceptibility/resistance. We think ducks with one unique type of gene are better at flu defense, and we will test that hypothesis by sampling blood and flu infection status of wild ducks in Alberta. Alberta is the convergence of several North American flyways, so is ideal for flu surveillance. This would be useful to know for duck farming, as well as conservation efforts aimed at maintaining a healthy population of wild ducks in the ecosystem. Three arms of the immune response are involved in clearing viruses; antibodies, adaptive immunity involving white blood cells that kill infected cells, and innate immunity. We believe that impaired adaptive immunity is responsible for the duck's exploitation as the host of most strains of influenza, while robust innate immunity allows them to survive highly pathogenic avian influenza. Our long-term goal is to understand these host-pathogen interactions from an immunology perspective, and understand the role of genetic diversity in host immune responses. Research goals focus on investigating gene order, diversity and expression in the MHC region of the genome. The genes that control the host immune response are located on one chromosome in the Major Histocompatibility Complex. The diversity of these genes in the species determines their success against viral pathogens. We are exploring the diversity of genes that control three kinds of white blood cells, the helper and cytotoxic T cells and the B cells that make antibodies. Different MHC genotypes have different immune responses to virus and to vaccines. We are also exploring other MHC-linked genes, called TRIM genes, which upregulate innate immune responses. Stronger innate responses are instructive for overall better immune responses. Antibody repertoire analyses of wild ducks may provide insight into generation of broadly neutralizing anti-influenza antibodies (the holy grail for influenza vaccines) and from experimental infections, therapeutics to combat highly pathogenic avian influenza. Here we examine the diversity and function of genes involved in controlling the duck immune response; 1) MHC class I that presents viral peptides to cytotoxic T cells, 2) MHC class II that presents particles taken up by macrophages and presented to helper T cells. Helper T cells turn on cytotoxic T cells and B cells that make antibodies; and 3) the MHC-linked TRIM27-L protein that turns up the innate immune response. Understanding the diversity of genes involved in defense against influenza in the reservoir host may help us understand selective forces driving evolution of influenza strains circulating in the environment.