Sequencing-based, culture-independent profiling of microbial communities has revealed a surprising degree of diversity in environmental and host-associated microbiomes. Now the burden on the field becomes understanding the fundamental mechanisms by which this diversity establishes and is maintained. My work is primarily concerned with the extent to which host-associated microbiomes are inherited genetically and then describing the host genomic architecture that underlies variation in microbiome structure and function.
During my postdoc I have relied on the threespine stickleback fish as an outstanding model for host-microbe interactions. Stickleback are great because we can leverage impressive standing genetic diversity across countless populations in environment-controlled experiments and in genotype-phenotype association studies (QTL mapping and GWAS). We can also manipulate the gut microbiome by making embryos “germ free” and adding controlled assemblages later during development. I have been fortunate to work with and learn from world-class microbiologists, geneticists, and physicists in the META Center of Excellence in Systems Biology at the UO to better understand host-microbe interactions in stickleback. Our recent work has shown impressive microbiome structure variation even among co-reared, closely related stickleback, despite their being a detectable, population-level genetic effect (see figure above). Ongoing work is identifying candidate regions of the stickleback genome that determine variation in the microbiome and in related host traits (like immune cell responses and gene expression patterns).
Current and future efforts are also focused on understanding the evolution of microbiomes in other fish host models. Hosts that live in highly specialized environments or have remarkable adaptations are promising candidates for exploring topics such as colonization, vertical transmission, and co-adaptation of hosts and microbes. Currently my colleagues and I are working to better understand microbiota associated with traits especially relevant to host reproduction, such as the male brooding tissues of syngnathid fishes. During my dissertation research on the genomics of male pregnancy, I was always curious about the roles microbes may be playing in processes like embryonic development, immune system regulation, and brood reduction. Fortunately, work in service of these ideas is now funded by an NSF “Rules of Life” grant, in collaboration with the Cresko Lab at the UO and the Jones Lab at the University of Idaho, including key help from syngnathid experts like Graham Short from Cal Academy of Sciences. Stay tuned for some exciting insights into the male pregnancy microbiome!
I’m also very interested in how host genetic variation shapes the fitness landscape of resident microbes (pathogens and commensals). Whether fitness landscapes are relatively smooth or rugged (see example above) can determine important evolutionary properties, like repeatability of adaptation and constraint, which are in principle critical for understanding microbial dynamics within the host from basic and translational research perspectives. I am beginning to take simulation-based and empirical approaches to understand the connection between host genetic variation and microbial evolution.