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.

项目概要 动物必须检测环境化学物质才能定位食物来源、识别捕食者并识别 伙伴们。气味检测所需的分子位于嗅觉感觉神经元的纤毛内。 嗅觉纤毛结构或感觉分子的运输和定位缺陷会导致嗅觉丧失， 这表明了解这些过程的生物学与人类健康高度相关。纤毛 结构的复杂性各不相同，这些形态决定了蛋白质的组成和组织 其中的信号分子。纤毛结构也可以被环境进一步改变，但 驱动这些改变的分子机制仍不清楚。尽管纤毛形态被认为是 塑造感觉反应的关键决定因素，纤毛结构在感觉信号转导中的作用， 尤其是对于嗅觉线索的反应，人们知之甚少。秀丽隐杆线虫感觉神经系统 是解决这些问题的理想模型。线虫中的单个化学感应神经元表现出 不同的纤毛形态，每种神经元类型都会对一组定义的化学物质做出反应，以驱动吸引力或 厌恶行为。与其他生物体一样，线虫纤毛拥有所有嗅觉受体和信号传导 分子。此外，嗅觉神经元纤毛的一个子集可以通过感觉活动进行重塑。这些特点， 结合其遗传易处理性和体内成像的适应性，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。该提案将 系统地探索特殊的纤毛形态如何促成独特的反应特征 线虫中的单个化学感应神经元，并将通过以下方式识别细胞和分子机制 这些纤毛形态通过感觉活动进一步改变。这项工作将为 了解化学感应信号传导中纤毛相关缺陷的发病机制。所描述的实验 在这个提案中将为我提供高分辨率显微镜、高分辨率定量技术方面的宝贵培训 通过体内钙进行化学感应行为分析和神经元功能定量分析 成像。此外，我的建议包括加强我在指导、网络和培训方面的培训的具体计划。 科学传播，这对于我成为一名独立研究员的目标至关重要。