Frank Schroeder - Toward comprehensive annotation of metazoan metabolomes: C. elegans as a model

How can we complement genomics and proteomics of animal model organisms such as C. elegans, Drosophila or mouse 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 unique metabolites reaching as high as several 10,000 in a single species. Our goal is to develop scalable approaches for structure elucidation and linking newly identified small molecule metabolites with genotypes and probable biological functions.

In this lecture, I will present structures and functions of several novel families 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.