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

动物与包括细菌在内的许多微生物生活在一起，统称为它们的微生物群。众所周知，微生物群调节着动物的发育和行为。然而，细菌（例如存在于肠道中的细菌）是如何影响动物发育和疾病的，人们知之甚少。秀丽隐杆线虫是一种微小的蠕虫，是一种被充分研究过的消耗细菌的实验生物。一些细菌存活下来并在蠕虫的肠道中定居，在那里它们产生影响蠕虫生理和行为的化学物质。初步结果表明，特定的细菌饮食可以改变这些蠕虫的社会和觅食行为。这个项目探索了细菌产生的化学物质如何针对蠕虫的神经系统来改变其行为。这些研究将确定细菌的化学物质和生产这些化学物质所需的基因，并确定在细菌中操纵这些基因如何影响蠕虫的神经系统。总之，这项研究提供了不同生物，特别是动物和相关微生物群之间的相互作用如何塑造其生命周期的详细描述。该研究项目支持高中生、本科生和研究生以及博士后的研究经验，并努力招募和参与这项工作中代表性不足的少数群体的成员。结果和基本的科学原理将通过在当地科学博物馆的实践演示、公开演讲和项目参与者参与当地的外展活动与公众分享。这项工作结合了神经科学家和化学家之间的合作，并以这种方式促进了跨学科的培训。微生物群在调节宿主生理和行为方面发挥着重要作用。细菌代谢物调节宿主神经元功能从而影响行为输出的机制尚不清楚。秀丽隐杆线虫（C. elegans）以细菌为食，在野外与多种细菌种类有关。共生细菌的一个子集可以存活并定植在蠕虫的肠道中。初步研究表明，秀丽隐杆线虫在特定菌株上的生长改变了它的探索行为，部分是通过调节特定信息素的产生。该项目结合了Sengupta实验室在秀丽隐杆线虫行为分析方面的互补专业知识和Schroeder实验室在代谢组学方面的专业知识，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神经系统功能的机制。具体来说，这项工作表征了细菌驱动的行为调节，确定了秀丽隐杆线虫的目标神经元，并表征了细菌代谢物改变神经元特性的机制。本研究利用细菌和秀丽隐杆线虫的遗传学，以及无偏倚的代谢组学，来识别和操纵细菌和线虫的生化途径，并表征这些操作对宿主行为的影响。这项跨学科合作的成果将为研究动物行为是如何受到特定有机体相互作用调控的机制提供新的见解。特别是，该项目将深入了解动物如何利用它们的微生物群来改变代谢途径，从而将它们的环境体验与行为可塑性结合起来。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.