Molecular Approaches To Fish Health – The Aeromonas salmonicida / Salmo salar Model System     Laura L. Brown1 , Stewart Johnson1, Jessica Boyd1, Andrew Dacanay1, Susan Douglas1, Roger Ebanks1, Vanya Ewart1, Yinong Han1, Victor Nesat1, Michael Reith1, Neil Ross1, Christoph Sensen2, Rama Singh1, Stephen Tsoi1   1National Research Council Canada, Institute for Marine Biosciences, 1411 Oxford Street, Halifax, NS, B3H 3Z1, Canada; 2Department of Biochemistry & Molecular Biology, Health Sciences Centre, University of Calgary, 3330 Hospital Drive, N.W., Calgary, AB T2N 4N1 Canada     Little is known about host-pathogen interactions in any species, including fish and humans.  Still less is known about these interactions at the molecular level, yet it is at that level that the most information is gained. The objective of this project is to develop an understanding of the molecular nature of host-pathogen interactions, using Atlantic salmon (Salmo salar) as host and Aeromonas salmonicida, as bacterial pathogen. We are taking an integrated two-pronged approach.  First, we are sequencing the entire genome of the bacterium, and analysis of the genome is being done through the Canadian Bioinformatics Resource.   Information gained from this large sequencing project will enable us to target potential antigens and other proteins that may have application as vaccine or immunomodulatory candidates.  Second, we are examining the functional genomics and proteomics of the A. salmonicida - S. salar relationship by examining the expressed genes and their protein products in both the pathogen and the host.  In vitro (with isolated fish cells) and in vivo (with live fish) challenges are carried out and samples of the bacterium and fish (or fish cells) taken at selected times during the infection.  From these samples, mRNA and proteins are isolated to determine which genes are expressed, which proteins are produced, and in what relative amounts during the infection process.  At the same time, immunological assays are carried out to complement the molecular information generated.  The genomic sequence will confirm the functional data, which will identify candidates for vaccines, immunomodulators, diagnostics, etc.  By linking genome sequencing, the functional genomics, proteomics and the immunological assays we are taking an integrated and innovative approach to pathogenesis research.  This will yield a wealth of information on the mechanisms of pathogenesis in general and A. salmonicida in particular.