Jason Crawford

High-throughput genome sequencing of bacteria and fungi has revealed many highly unusual “orphan” biosynthetic gene clusters suspected of synthesizing novel, structurally diverse, and biologically active small molecules. These types of naturally produced molecules often regulate complex interactions with their animal hosts, hold a rich history of being utilized as human drugs, and serve as excellent molecular probes for identifying new drug targets for a wide variety of diseases. Here, we will highlight our efforts on decoding the biosynthesis, structure, and function of bioactive small molecules encoded by the human microbiome with an emphasis on their regulation of human cellular responses. We will cover examples of molecular communication between bacteria and human cells and the forward versus reverse genetic approaches to illuminate them.