The role of sensory cilia architecture in shaping chemosensory neuron responses

感觉纤毛结构在塑造化学感觉神经元反应中的作用

• 批准号: 9907103
• 负责人: Alison Philbrook
• 金额: $ 6.12万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-16 至 2021-12-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9907103
• 关键词: Acute; Address; Affect; Afferent Neurons; Animals; Anosmia; Architecture; Area; Automobile Driving; Behavior; Biology; Caenorhabditis elegans; Chemicals; Cilia; Communication; Complex; Cues; Defect; Detection; Environment; Equilibrium; Exhibits; Food; Genes; Genetic; Goals; Health; Hearing; Human; Individual; Laboratory Organism; Lead; Mediating; Membrane; Membrane Proteins; Mentorship; Microscopy; Modeling; Molecular; Morphology; Mutation; Nervous system structure; Neurons; Odorant Receptors; Organism; Partner in relationship; Pathogenesis; Phospholipids; Photoreceptors; Phototransduction; Play; Process; Proteins; Regulation; Research; Research Personnel; Resolution; Role; Sensory; Shapes; Signal Transduction; Signaling Molecule; Signaling Protein; Smell Perception; Source; Stimulus; Structure; System; Training; Work; base; environmental chemical; experimental study; in vivo calcium imaging; in vivo imaging; individual response; mutant; nervous system disorder; olfactory receptor; olfactory sensory neurons; response; sensory input; trafficking

Project summary Animals must detect environmental chemicals in order to locate food sources, recognize predators, and identify mates. Molecules necessary for odorant detection are housed within the cilia of olfactory sensory neurons. Defects in olfactory cilia structure, or the trafficking and localization of sensory molecules, result in anosmia, suggesting that understanding the biology of these processes is highly relevant to human health. Cilia structures range in complexity, and these morphologies dictate protein composition and the organization of signaling molecules within them. Cilia structure can also be further modified by the environment, but the molecular mechanisms driving these alterations remain unclear. Although cilia morphology is thought to be a critical determinant for shaping sensory responses, the role of cilia architecture in sensory signal transduction, and in particular for responses to olfactory cues, is poorly understood. The C. elegans sensory nervous system is an ideal model in which to address these questions. Individual chemosensory neurons in C. elegans exhibit diverse cilia morphologies, and each neuron type responds to a defined set of chemicals to drive attraction or aversion behaviors. As in other organisms, C. elegans cilia house all olfactory receptors and signaling molecules. Moreover, a subset of olfactory neuron cilia can be remodeled by sensory activity. These features, combined with its genetic tractability and amenability to in vivo imaging, provide a unique opportunity to elucidate key mechanisms responsible for shaping cilia morphology and function. This proposal will systematically explore how specialized cilia morphologies contribute to the unique response profiles of individual chemosensory neurons in C. elegans, and will identify the cellular and molecular mechanisms by which these cilia morphologies are further modified by sensory activity. This work will provide a framework for understanding the pathogenesis of cilia-related defects in chemosensory signaling. The experiments described in this proposal will provide me with valuable training in high-resolution microscopy, high-resolution quantitative analyses of chemosensory behaviors, and quantitative analyses of neuronal function via in vivo calcium imaging. Further, my proposal includes concrete plans to enhance my training in mentorship, networking, and scientific communication, areas that are critical for my goal to become an independent researcher.

项目摘要 动物必须检测到环境化学物质，以找到食物来源，识别捕食者并识别 伴侣。气味检测所需的分子位于嗅觉感觉神经元的纤毛内。 嗅觉纤毛结构的缺陷或感觉分子的运输和定位导致厌食 暗示了解这些过程的生物学与人类健康高度相关。纤毛 结构的复杂性范围，这些形态决定了蛋白质组成和组织 其中的信号分子。环境也可以进一步修改纤毛结构，但是 驱动这些改变的分子机制尚不清楚。尽管纤毛形态被认为是 构成感觉响应的关键决定因素，纤毛结构在感觉信号转导中的作用， 特别是对于嗅觉提示的响应，人们的理解很少。秀丽隐杆线虫感官神经系统 是解决这些问题的理想模型。秀丽隐杆线虫中的单个化学感应神经元展示 多种纤毛形态，每种神经元类型都对一组定义的化学物质响应，以吸引吸引力或 厌恶行为。与其他生物一样，秀丽隐杆线虫纤毛屋所有嗅觉受体和信号传导 分子。此外，可以通过感觉活动来重塑嗅觉神经元的一部分。这些功能， 结合其遗传障碍性和体内成像的舒适性，为您提供了独特的机会 阐明负责塑造纤毛形态和功能的关键机制。该提议将 系统地探讨专业的纤毛形态如何促进 秀丽隐杆线虫中的个体化学感应神经元，将通过 这些纤毛形态通过感觉活动进一步改变。这项工作将为 了解化学感信号传导中纤毛相关缺陷的发病机理。描述的实验 在此提案中，将为我提供高分辨率显微镜，高分辨率定量的宝贵培训 通过体内钙的化学感应行为分析和神经元功能的定量分析 成像。此外，我的建议还包括具体计划，以增强我在指导，网络方面的培训和 科学沟通，对于我成为独立研究人员目标至关重要的领域。