Determining the Role of Bacterial Products on Neuronal Localization and Function in a Symbiotic Organ

确定细菌产物对共生器官神经元定位和功能的作用

• 批准号: 10647940
• 负责人: Elizabeth A. Heath-Heckman
• 金额: $ 18.78万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10647940
• 关键词: Activities of Daily Living; Address; Adolescent; Affect; Animals; Apoptosis; Bacteria; Biological Models; Biology; Brain; Central Nervous System; Characteristics; Communities; Complex; Data; Development; Embryonic Development; Enteral; Enteric Nervous System; Epithelium; Euprymna scolopes; FMRFamide; Foundations; Genes; Genetic; Goals; Hawaiian; Hindgut; Image; Imaging Techniques; In Situ Hybridization; Individual; Knowledge; Label; Light; Lipopolysaccharides; Location; Mediating; Methods; Microbe; Modeling; Nervous System; Neurobiology; Neuronal Plasticity; Neurons; Neuropeptides; Neurotransmitters; Nitric Oxide; Optics; Organ; Outcome; Pathway interactions; Peptidoglycan; Peripheral Nervous System; Phenotype; Physiology; Positioning Attribute; Postembryonic; Process; Production; Proteins; RNA; Reaction; Resources; Role; Signal Transduction; Source; Squid; Structure; Study models; Surface; Symbiosis; System; Techniques; Testing; Time; Tissues; V. fischeri-squid system; Vibrio; Vibrio fischeri; Visualization; Whole Organism; Work; appendage; beneficial microorganism; connectome; gene product; gut microbiome; hatching; immunocytochemistry; innovation; insight; interest; microbial; microbiome; mutant; mutualism; neurodevelopment; neuron development; pharmacologic; receptor; response; symbiont; transcriptome sequencing

PROJECT SUMMARY Bacteria, such as those found in the vertebrate gut microbiome, have been shown to have widespread effects on both the enteric (ENS) and central nervous systems (CNS) in numerous animals. Reciprocally, the ENS has been shown to have an impact on the progression of microbiome establishment in the gut. However, despite the profound influence of bacteria on neuronal development and physiology, the diversity of the vertebrate gut microbiome and the complexity of the ENS make the mechanisms underlying these phenomena difficult to study. Despite the importance of the topic and vertebrate models, these systems involve microbiomes that are both spatially and compositionally complex, often with thousands of bacterial species that can very between individual hosts. Therefore there is a role for simple, exquisitely manipulable model systems in which to study the effects of bacterial symbionts on neuronal development and function. To address the dearth of such models for the mechanisms by which bacteria influence host neurobiology, we propose to use the symbiosis between the Hawaiian bobtail squid (Euprymna scolopes) and its luminescent bacterial symbiont Vibrio fischeri as a tractable system in which to study how bacteria drive host neuronal development. The squid-vibrio system is a well-established model for the effects of bacterial products on host physiology and development, with outcomes that are often generalizable to other animal systems. This proposal aims to develop the squid-vibrio system into a new model for the study of the effects of microbes on host neurobiology. In our first aim we will define the neuronal landscape of the light organ, including neuronal position and identity and the effect of symbiosis and bacterial products on both. To achieve this aim, we will develop new methods for dual labeling of RNA and proteins in our system and adapt neuronal tracing techniques for imaging in the light organ. In our second aim we propose to study the role of neuropeptide signaling on transducing microbial signals from V. fischeri to tissues on the outside of the symbiotic organ. Specifically, we will determine the location and dynamics of FMRFamide signaling in the light organ over the first three days of symbiosis and will examine the effects of FMRFamide signaling on bacterially-mediated post-embryonic development. The data arising from this proposal will not only lay the foundation for a powerful new model system, but will also generate new resources and techniques for the community and provide new insights as to the role of the peripheral nervous system in potentiating microbially-mediated development.

项目摘要 细菌，例如在脊椎动物肠道微生物组中发现的细菌，已显示出广泛的 对众多动物的肠道（ENS）和中枢神经系统（CNS）的影响。相互 ENS已被证明对肠道中微生物组的发展有影响。然而， 尽管细菌对神经元发育和生理学产生了深远的影响，但多样性的多样性 脊椎动物肠道微生物组和ENS的复杂性使这些现象的基础 难以学习。尽管主题和脊椎动物模型很重要，但这些系统涉及 在空间和组成上既复杂又有微生物组，通常有成千上万的细菌物种 可以在单个主机之间非常适合。因此，简单，精美​​的可操纵模型系统有角色 在其中研究细菌共生体对神经元发育和功能的影响。解决 对于细菌影响宿主神经生物学的机制的缺乏，我们建议使用 夏威夷bobtail鱿鱼（Euprymna scolopes）及其发光细菌共生体之间的共生 Vibrio Fischeri是一种可探讨细菌如何驱动宿主神经元发育的系统。这 鱿鱼 - 挥舞式系统是一个完善的模型，用于细菌产品对宿主生理学和 发展，其结果通常可以推广到其他动物系统。该建议旨在 将鱿鱼 - 颤音系统开发为一种新模型，以研究微生物对宿主神经生物学的影响。 在我们的第一个目标中，我们将定义光器官的神经元景观，包括神经元位置和身份 以及共生和细菌产物对两者的影响。为了实现这一目标，我们将开发新的方法 用于我们系统中RNA和蛋白质的双重标记，并适应神经元跟踪技术以成像 轻型器官。在我们的第二个目标中，我们建议研究神经肽信号传导在转导微生物中的作用 从V. fischeri到共生器官外部​​的组织的信号。具体来说，我们将确定 在共生的前三天，FMRFAMIDE信号传导的位置和动力学 检查FMRFAMIDE信号传导对细菌介导的胚胎后发育的影响。数据 该提案引起的不仅会为强大的新模型系统奠定基础，而且还将 为社区生成新的资源和技术，并就有关的作用提供新的见解 外周神经系统在增强微生物介导的发育中。