Small-Molecule Pheromones that Induce Dauer Formation

描述（由申请人提供）：在C。在线虫中，进入发育停滞的“非老化”幼仔阶段的决定主要由分泌的幼仔信息素控制。道尔信息素的小分子成分包括几种蛔虫素衍生物，其与信息素的其他未鉴定的成分协同作用以诱导道尔形成。详细了解这些诱导dauer的小分子及其作用机制，将使化学工具的发展，用于研究dauer形成和相关过程的研究，如发展，代谢和老化。在这个建议中，我们将充分表征的dauer信息素进行结构活性研究的蛔虫，通过识别未知的信息素成分的化学结构显示协同活性与蛔虫，通过表征的信息素成分的作用机制，使用上位性分析，并通过转录分析C。用信息素成分处理的线虫。通过阐明小分子信息素如何影响C。elegans的发展，我们的研究可能最终提供洞察环境线索如何影响人类的发展，新陈代谢和衰老。

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.