Boyce Thompson Institute
Department of Chemistry and Chemical Biology
Host: Oliver Hobert
Title: Uncovering the "Dark Matter" of the Chemistry of Life: a Universe of Signaling Molecules
Abstract: How can we complement genomics and proteomics of animal model organisms such as C. elegans or Drosophila with a comprehensive structural and functional annotation of the corresponding metabolomes? Growing evidence suggests that small molecules of largely undetermined structure play important roles in the biology of microorganisms, animals, and their mutual interactions, affecting key physiological pathways that regulate lifespan, development, and metabolism, with estimates for the number of metabolites ranging from 10,000 to several 100,000 in a single species.
Our goal is to develop a systematic approach for linking small molecule metabolites directly with genotypes and probable biological functions. In this lecture, I will present several novel types of small molecule signals we recently identified in the nematode C. elegans. We found that, using simple building blocks from conserved primary metabolism and a strategy of combinatorial assembly, C. elegans and other nematode species create complex molecular architectures to regulate almost every aspect of their life history. The resulting signaling molecules can be active at femtomolar concentrations, changing behavior, development, of lifespan by modulating conserved insulin or nuclear hormone receptor signaling. The discovery of new types of modular, primary metabolism-derived signaling molecules in C. elegans provides a strong incentive for a comprehensive re-analysis of metabolism in higher animals, including humans.