Small-Molecule Pheromones that Induce Dauer Formation

诱导 Dauer 形成的小分子信息素

• 批准号: 7113324
• 负责人: Rebecca A Butcher
• 金额: $ 4.4万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7113324
• 关键词: Caenorhabditis elegans; aging; chemical structure function; growth /development; invertebrate hormone; larva; pheromone; postdoctoral investigator; small molecule

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.

描述（由申请人提供）：在秀丽隐杆线虫中，决定进入发育停滞、“非衰老”的 dauer 幼虫阶段主要由分泌的 dauer 信息素控制。多尔信息素的小分子成分包括几种蛔糖衍生物，它们与信息素的其他未识别成分协同作用，诱导多尔信息素形成。详细了解这些诱导多尔的小分子及其作用机制，将有助于开发用于研究多尔形成以及发育、代谢和衰老等相关过程的化学工具。在本提案中，我们将通过对蛔苷进行结构活性研究，通过鉴定与蛔苷具有协同活性的未知信息素成分的化学结构，通过使用上位分析表征信息素成分的作用机制，来充分表征dauer信息素，并通过转录分析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线虫发育，我们的研究最终可能为环境因素如何影响人类发育、新陈代谢和衰老提供见解。