Collaborative Research: Modulation of pheromone-dependent host behavior by gut bacteria

合作研究：肠道细菌调节信息素依赖性宿主行为

• 批准号: 2042101
• 负责人: Frank Schroeder
• 金额: $ 35.29万
• 依托单位: Boyce Thompson Institute Plant Research
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2042101&HistoricalAwards=false
• 关键词: Collaborative; Research; Modulation; pheromone; dependent

Animals live in association with many microorganisms including bacteria, collectively referred to as their microbiota. Microbiota are now well known to regulate development and behaviors of animals. However, how bacteria, present for example in the gut, influence animal development and disease is poorly understood. The nematode C. elegans, a tiny worm, is a well-studied experimental organism that consumes bacteria. Some bacteria survive and colonize the worm gut, where they produce chemicals that influence worm physiology and behavior. Preliminary results indicate that specific bacterial diets can change social and food-finding behaviors of these worms. This project explores how chemicals made by the bacteria target the worm’s nervous system to alter its behaviors. The studies will identify the bacterial chemicals and genes required for production of the chemicals and determine how manipulating these genes in the bacteria affect the worm’s nervous system. Together, this research provides a detailed description of how interactions among different organisms, specifically animals and associated microbiota, shape their life cycles. The research program supports the research experiences of high school, undergraduate and graduate students, and postdoctoral fellows with efforts made to recruit and involve members of underrepresented minority groups in this work. Results and foundational scientific principles will be shared with the public via hands-on demonstrations at local science museums, via public presentations, and by the involvement of project participants in local outreach activities. This work incorporates a collaboration between neuroscientists and chemists, and promotes interdisciplinary training in this way.Microbiota are now well-established to play critical roles in modulating host physiology and behavior. The mechanisms by which bacterial metabolites regulate host neuronal functions to influence behavioral outputs is unclear. The nematode C. elegans consumes bacteria and is associated with diverse bacterial species in the wild. A subset of commensal bacteria can survive and colonize the worm gut. Preliminary work indicates that growth of C. elegans on specific bacterial strains alters its exploratory behavior, in part via the regulation of production of specific pheromones. The project combines the complementary expertise of the Sengupta lab in C. elegans behavioral analysis and the Schroeder lab in metabolomics to describe the mechanisms by which the interaction of C. elegans with specific bacterial strains alters the host’s nervous system functions. Specifically, the work characterizes bacteria-driven behavioral modulation, identifies the targeted neurons in C. elegans, and characterizes the mechanisms by which bacterial metabolites alter neuronal properties. This research uses bacterial and C. elegans genetics, as well as unbiased metabolomics, to identify and manipulate bacterial and nematode biochemical pathways, and characterize the effects of these manipulations on host behavior. Results from this collaborative and interdisciplinary work will provide new insights into the mechanisms by which animal behavior is regulated in response to specific organismal interactions. In particular, the project will provide insights into how animals leverage their microbiota to alter metabolic pathways, thereby coupling their environmental experiences with behavioral plasticity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

动物与包括细菌在内的许多微生物相关，统称为菌群。现在众所周知，微生物群可以调节动物的发育和行为。但是，例如在肠道中存在的细菌如何影响动物的发育和疾病。线虫C.秀丽隐杆线虫是一种小蠕虫，是一种经过良好的实验生物，可消耗细菌。一些细菌在蠕虫肠道上生存并定居，它们产生影响蠕虫生理和行为的化学物质。初步结果表明，特定细菌饮食可以改变这些蠕虫的社交和食物调查行为。该项目探讨了细菌产生的化学物质是如何针对蠕虫神经系统来改变其行为的。这些研究将确定产生化学物质所需的细菌化学物质和基因，并确定细菌中这些基因如何影响蠕虫神经系统。这项研究共同提供了详细的描述，描述了不同组织之间的相互作用如何塑造其生命周期。该研究计划支持高中，本科生和研究生以及博士后研究员的研究经历，并努力招募招募，并参与代表性不足的少数群体的成员。结果和基本科学原则将通过当地科学博物馆，公开演示以及项目参与者参与当地外展活动的参与与公众共享。这项工作结合了神经科学家和化学家之间的合作，并以这种方式促进跨学科培训。现在已经建立了良好的成就，可以在调节宿主生理和行为中发挥关键作用。细菌代谢物调节宿主神经元功能以影响行为输出的机制尚不清楚。线虫秀丽隐杆线虫会消耗细菌，并与野外潜水细菌物种相关。共生细菌的一部分可以生存并定居蠕虫肠。初步工作表明，秀丽隐杆线虫对特定细菌菌株的生长改变了其探索行为，部分是通过调节特定信息素的生产来改变的。该项目结合了秀丽隐杆线虫行为分析中的Sengupta实验室的完整专业知识和代谢组学中的Schroeder Lab，以描述秀丽隐杆线虫与特定细菌菌株的相互作用改变宿主的神经系统功能的机制。具体而言，这项工作表征了细菌驱动的行为调制，鉴定了秀丽隐杆线虫中的靶向神经元，并表征了细菌代谢物改变神经元特性的机制。该研究使用细菌和秀丽隐杆线虫遗传学以及无偏的代谢组学来识别和操纵细菌和线虫生化途径，并表征这些操纵对宿主行为的影响。这项协作和跨学科工作的结果将为对特定的有机相互作用而调节动物行为的机制提供新的见解。特别是，该项目将提供有关动物如何利用其微生物群来改变代谢途径的见解，从而将其环境经历与行为可塑性结合在一起。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子和更广泛影响的审查标准来评估的珍贵支持。