Small-Molecule Pheromones that Induce Dauer Formation

描述（由申请人提供）：在秀丽隐杆线虫中，决定进入发育迟缓，“非衰老”的dawer幼虫阶段主要是由分泌的dawer信息素控制的。道尔信息素的小分子成分包括几种丝氨酸衍生物，它们与信息素的其他未识别成分协同作用，诱导道尔形成。详细了解这些诱导道尔的小分子及其作用机制，将有助于开发用于研究道尔形成和研究相关过程（如发育、代谢和衰老）的化学工具。在本研究中，我们将通过对蛔虫苷进行结构-活性研究，通过鉴定与蛔虫苷具有协同活性的未知信息素成分的化学结构，通过上位性分析表征信息素成分的作用机制，以及通过对信息素成分处理过的秀丽隐杆线虫的转录谱分析来充分表征信息素。通过阐明小分子信息素如何影响秀丽隐杆线虫的发育，我们的研究可能最终为环境因素如何影响人类发育、代谢和衰老提供见解。

DESCRIPTION (provided by applicant): In C. elegans, the decision to enter a developmentally arrested, 'non-aging' dauer larval stage is primarily controlled by a secreted dauer pheromone. Small-molecule components of the dauer pheromone include several ascarylose derivatives, which work synergistically with other unidentified components of the pheromone to induce dauer formation. A detailed understanding of these dauer-inducing small molecules and their mechanism of action would enable the development of chemical tools for the study of dauer formation and for the study of related processes such as development, metabolism, and aging. In this proposal, we will fully characterize the dauer pheromone by performing structure-activity studies on the ascarosides, by identifying the chemical structures of unknown pheromone components showing synergistic activity with the ascarosides, by characterizing the mechanism of action of the pheromone components using epistasis analysis, and by transcriptionally profiling C. elegans treated with the pheromone components. By elucidating how small-molecule pheromones influence C. elegans development, our research may ultimately provide insights into how environmental cues influence human development, metabolism and aging.