PROJECT SUMMARY/ABSTRACT
Human-associated microbes are causally linked to processes as diverse as immunomodulation, protection
against pathogens, and atherosclerosis. Many of these links are mediated through biochemical transformations
of dietary, drug, or host compounds. This makes the microbiome a promising therapeutic target, especially as
we could potentially affect downstream processes by controlling metabolic inputs. However, in order to
effectively intervene, we must first understand how exactly changes in these inputs lead to differential
regulation of growth, gene expression, and metabolism. This is challenging because our microbiomes are not
only genetically and physiologically diverse, but are also highly diverged from the most common model
organisms, with many genes of unknown function.
Over the next five years, my research group will use a combined computational and experimental strategy
to characterize gene function, metabolic regulation, and microbial interactions in one of the most prevalent and
abundant clades of gut bacteria, the Bacteroidales. Specifically, we seek to determine 1) which Bacteroidales
genes are involved in growth on different nutrients and stressors; 2) how Bacteroidales genes are regulated,
and how this affects their metabolic outputs; and 3) how Bacteroidales interact with the other microbial
inhabitants of the gut. We will accomplish this by gathering high-throughput in vitro data from diverse sets of
microbiome isolates and synthetic communities, developing more powerful and specific statistical tools to
analyze these data, and using these new data and tools to re-analyze metagenomics data gathered from in
vivo case-control studies. I envision that this line of inquiry will provide missing fundamental knowledge about
this clade of microbes, which will ultimately help us interpret case-control studies of the microbiome and
support the development of more precise interventions.