The Schroeder lab aims to complement the highly developed genomics and proteomics of C. elegans with a comprehensive structural and functional characterization of its metabolome. Our recent investigations have shown that a family of C. elegans small molecules, the ascarosides, function as key regulators of ageing, developmental timing, and behavior. Using a comparative metabolomics approach, we have identified a modular library of small molecule signals, which are derived from combinatorial assembly of building blocks from several conserved metabolic pathways, including carbohydrate, amino acid, nucleic acid, and lipid metabolism. We show that these molecules are associated with specific biological functions, and that different compound combinations and concentrations result in divergent phenotypes. Examples include endogenous signaling molecules that regulate C. elegans lifespan in a SIR-2.1-dependent manner, compounds that control adult phenotypic plasticity in a nuclear hormone receptor-dependent manner, as well as compounds that regulate the behavior of parasitic nematodes. We show further show that lifespan regulation by ascarosides involves binding to highly specific G-protein coupled receptors that are expressed in several sets of sensory neurons and function upstream of conserved signaling pathways.

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