Grant: CIHR Fellowship

Bacteria that cause disease use a wide variety of mechanisms to control their environment. In particular, bacteria that invade host cells and use them to replicate, such as the bacterium responsible for the majority of food-poisoning cases in Canada, Salmonella, are adept at modifying their environments. Salmonella must subvert the routines of immune cells of the host that would normally prevent infection. As part of this subversion, salmonella alters normal host cell signaling pathways, preventing immune functions. Disruption to host signaling pathways often results in increases or decreases in expression of immune response genes. One method the host uses to alter expression of its own genes is to modify the chromosome at specific genes, either by modifying the chromosome itself, or by modifying the proteins that package the chromosome, called histones. Such modifications to chromatin are referred to as the "epigenetic code" of the host. Some bacteria produce proteins that can interact with the host chromatin to make additional changes to the epigenetic code of the host, and therefore generate a more favorable environment for replication. I hypothesize that salmonella are also able to modify the host epigenetic code, and that these modifications are important for salmonella survival and replication in the host. I will show that salmonella infection induces changes in the epigenetic code, and that these changes are the direct effect of salmonella proteins.