In C. e/egans, the decision to enter a developmentally arrested, 'non-aging' dauer larval stage is primarilycontrolled by a secreted dauer pheromone. Small-molecule components of the dauer pheromone includeseveral ascarylose derivatives, which work synergistically with other unidentified components of thepheromone to induce dauer formation. A detailed understanding of these dauer-inducing small moleculesand their mechanism of action would enable the development of chemical tools for the study of dauerformation and for the study of related processes such as development, metabolism, and aging. In thisproposal, we will fully characterize the dauer pheromone by performing structure-activity studies on theascarosides, by identifying the chemical structures of unknown pheromone components showingsynergisticactivity with the ascarosides, by characterizing the mechanism of action of the pheromone components usingepistasis analysis, and by transcriptionally profiling C. e/egans treated with the pheromone components. Byelucidating how small-molecule pheromones influence C. e/egans development, our research may ultimatelyprovide insights into how environmental cues influence human development, metabolism and aging.
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