CAREER: Investigating the role of MHC during assembly of commensal microbial communities

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Mammals are home to a vast consortium of commensal bacteria that help shape and maintain host health. While some resident microbes have beneficial consequences to the host, others are detrimental. Pathogenic and commensal bacteria share many of the same molecular motifs, making it unclear how the host immune system discriminates between beneficial and harmful bacterial species. Vertebrates possess a unique gene family, the major histocompatibility complex (MHC),that allows for activation of a tailored immune response toward a specific microbe. The fundamental function of the MHC gene locus is to allow the immune system to discriminate between "self" and "non-self" tissue, thus allowing the immune system to destroy microbial invaders, while preventing the immune system from attacking cells of the animal's own body. However, the investigators propose an additional, thus far un-appreciated role for the MHC: that a major driving force in the evolution of the MHC, beyond its long-known roles in animal "self" recognition and eradication of pathogens, is the need for animals to maintain a homeostatic relationship with their commensal microbial communities. This project will test this novel hypothesis using genetic and molecular approaches coupled with microbiota transfers into germfree mice. These studies have the potential to reveal how microbial communities are constructed within the host and to identify novel principles by which the host and microbes communicate. If the MHC is proven to govern the assembly of commensal communities, then animal "self" will need to be redefined to include not just the host animal itself, but also the animal's commensal microbiota. Educational goals of this project include research training for undergraduate, graduate and postdoctoral students. In addition, the investigator and her students will work with staff of a local natural history museum to create a summer science camp that teaches middle school children about their own commensal microbiota.