Natural products -- small molecules from microbes -- are used widely in the clinic as antibiotics, anticancer agents, immunosuppressants, and cholesterol-lowering drugs. Our lab focuses on three emerging principles that are changing our understanding of which microbes make natural products, what roles they play in the biology of their producers, and how best to discover them:
1. Natural products are produced by the human microbiota.
Most known natural products come from exotic soil and marine bacteria. We have recently found that bacteria from a surprisingly underexplored niche -- the human body -- are prolific producers of natural products. We are currently mining gut- and skin-associated bacteria for natural products that play important roles in human physiology and disease.
2. Natural products mediate microbe-host and microbe-microbe interactions.
We are particularly interested in the mechanisms by which natural products from the human microbiome mediate interspecies interactions. We are focusing on interactions between gut bacteria and humans that are relevant to human diseases like Crohn's disease and obesity, and on interactions between different species of skin bacteria that likely play a role in susceptibility to infection by bacterial pathogens like Staphylococcus aureus.
3. Connecting natural products to the genes that encode them accelerates discovery.
We are developing a bioinformatic algorithm that automatically identifies clusters of small-molecule-producing genes in bacterial genomes. An early version of this algorithm has already identified thousands of new gene clusters in the thousands of bacterial genomes sequenced to date, many of them in species from the human microbiome. We are refining this algorithm so it can predict the chemical structure of the small molecule encoded by each gene cluster. In the near future, we believe this tool will provide us the first global view of the small molecules produced by bacteria, which will serve as a powerful predictive tool for our experimental efforts.