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Functional Pathogenomics of Mucosal Immunity

  • Project Leaders: Bob Hancock, Lorne Babiuk
  • Institutions: University of British Columbia (UBC)
  • Budget: $9700000
  • Program/Competition: Large Scale Competitions
  • Genome Centre(s): Genome Canada
  • Status: Closed

Despite being exposed to tens of thousands of potentially pathogenic microbes daily, we rarely succumb to infection, primarily due to our innate immune system. This ‘innate-immunity’ defense system can be over-stimulated, and result in excessive inflammation, leading to tissue damage and deadly syndromes like sepsis. A previous project in pathogen:host interactions (Functional Pathogenomics of Mucosal Immunity- $9.7M UBC/VIDO) discovered which genes were up-regulated during the triggering of innate immunity as well as a novel therapeutic approach to infectious diseases that selectively boosts innate immunity while suppressing harmful inflammation. This project collaborated with the Sanger Institute’s Mouse Genomics Program to characterize selected genes in response to Salmonella infection in mouse models. Deleting specific genes, the relevance in human and animal infections was able to be determined. This project investigated the upregulation of innate immunity to determine the points of intervention that will allow control of infection without harmful inflammation. This project also involves international partnerships with the National University of Singapore, and the Trinity College Dublin. The project also created multiple tools for use by researchers, including the InnateDB bioinformatics database in which greater than 14,000 innate immunity-relevant interactions, involving over 3,800 genes, were contextually annotated. This database received over 1 million user hits per year globally in the final two years of the project. Some of the outputs were used to generate novel peptides for pre-clinical development.