Defensin Regulation of Human Gut Microbial Communities
Humans are 'supra-organisms': composites of human and microbial cells whose genomes complement our own. Recent work by myself and others has shown that the 'normal' gut microbiota can contribute to disease in susceptible hosts. A deep understanding of human health and disease must include characterizations of the factors that influence the variations, assembly, stability, and functions of our microbiota. This research uses both in-vivo and novel in-vitro approaches to test the hypotheses that endogenous anti-microbial peptides (defensins) secreted in the gut, and whose activity is poorly defined, shape the composition of the gut microbiota by selective killing. A microfluidic-based high throughput in-vitro system will be developed to test the activity of defensins against mixed bacterial communities of two types: (1) synthetic communities assembled from microbes whose genome sequences are available through the Human Microbiome Project, and (2) complex communities derived from healthy human donors. We will use next generation sequemcers to produce metagenomic datasets and apply network-based analysis tools to infer how defensins shape microbial community composition and function. Our in-vivo model will consist of defensin-deficient inbred mice whose guy microbiotas will be compared to those of wildtype mice. Thise research will show how the host genome regulates community composition through the production of antimicrobial peptides. Furthermore, this research will provide critical information for the production of a new generation of antibiotics.
Arnold O. Beckman exemplifies the meaning of the word humanitarian. Combined with his unwavering enthusiasm for life, his keen sense of humor and his strong moral and ethical principles, he is a national icon.