The goal of our research program is to improve human health through the discovery of molecules and pathways that mediate physiology and disease. The focus on biology related to metabolites and peptides, which we refer to as natural small molecules, distinguishes our research program. Natural small molecules have vital roles in human physiology and disease; the peptide hormone insulin, for example, controls physiological glucose levels and undergoes aberrant signaling in diabetes. A lack of available experimental tools, however, has made natural small molecules more difficult to study than genes or proteins. It is our belief that the development of a systematic approach towards the investigation of natural small molecules in biology will lead to fundamental discoveries about the molecular basis of disease.