The role of sensory cilia architecture in shaping chemosensory neuron responses

项目摘要 动物必须探测环境中的化学物质，以确定食物来源，识别捕食者，并识别 伙计们气味检测所需的分子位于嗅觉神经元的纤毛内。 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 结构的复杂性范围，这些形态决定了蛋白质的组成和组织 其中的信号分子。纤毛结构也可以进一步修改的环境，但 驱动这些改变的分子机制仍不清楚。虽然纤毛形态被认为是一种 形成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， 特别是对嗅觉线索的反应，知之甚少。梭感觉神经系统 是解决这些问题的理想模式。C.优雅展品 不同的纤毛形态，每种神经元类型对一组确定的化学物质作出反应，以驱动吸引力或 厌恶行为与其他生物一样，C.秀丽线虫纤毛容纳所有的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。这些特征， 结合其遗传易处理性和对体内成像的顺从性，提供了一个独特的机会， 阐明负责纤毛形态和功能形成的关键机制。这项建议会 系统地探讨如何专门纤毛形态有助于独特的反应概况， C.线虫，并将确定细胞和分子机制， 这些纤毛形态进一步被感觉活动改变。这项工作将提供一个框架， 了解化学感受信号中纤毛相关缺陷的发病机制。描述的实验 在这个建议将为我提供宝贵的培训，在高分辨率显微镜，高分辨率定量 化学感受行为分析，以及通过体内钙离子定量分析神经元功能 显像此外，我的建议包括具体的计划，以加强我在指导，网络， 科学交流，这些领域对我成为一名独立研究人员的目标至关重要。

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.