While decades of study of model organisms have revolutionized our understanding of the microbial world, the vast majority of human-associated microorganisms are still “wild”—they lack functional tools to enable their functional interrogation. Our research group is working to build generalizable approaches to discover and characterize the bacterial species, genes, and enzymes relevant to human disease, with a particular focus on the gut bacterial metabolism of non-antibiotic drugs and diet-derived compounds. I will discuss our initial efforts focused on Eggerthella lenta, a poorly-studied but prevalent human gut Actinobacterium thought to play a key role in metabolism and pathogenesis. These inter-disciplinary studies utilize a combination of metagenomic analysis, comparative genomics, heterologous expression, and biochemistry. Finally, I will discuss our ongoing efforts to establish a novel genetic tool that leverages the endogenous gut bacterial CRISPR-Cas system of E. lenta to target specific genes of interest. Together, these results provide a foundation for developing modular tools for predicting gut microbial metabolism and the rational design of microbial communities for a desired outcome.
Domesticating Human Gut Bacteria to Gain Mechanistic Insights
into the Etiology and Treatment of Disease
Professor, Department of Microbiology & Immunology
University of California, San Francisco