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
基本信息
- 批准号:9907103
- 负责人:
- 金额:$ 6.12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AcuteAddressAffectAfferent NeuronsAnimalsAnosmiaArchitectureAreaAutomobile DrivingBehaviorBiologyCaenorhabditis elegansChemicalsCiliaCommunicationComplexCuesDefectDetectionEnvironmentEquilibriumExhibitsFoodGenesGeneticGoalsHealthHearingHumanIndividualLaboratory OrganismLeadMediatingMembraneMembrane ProteinsMentorshipMicroscopyModelingMolecularMorphologyMutationNervous system structureNeuronsOdorant ReceptorsOrganismPartner in relationshipPathogenesisPhospholipidsPhotoreceptorsPhototransductionPlayProcessProteinsRegulationResearchResearch PersonnelResolutionRoleSensoryShapesSignal TransductionSignaling MoleculeSignaling ProteinSmell PerceptionSourceStimulusStructureSystemTrainingWorkbaseenvironmental chemicalexperimental studyin vivo calcium imagingin vivo imagingindividual responsemutantnervous system disorderolfactory receptorolfactory sensory neuronsresponsesensory inputtrafficking
项目摘要
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.
项目总结
动物必须检测环境中的化学物质,以便定位食物来源,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,会导致嗅觉障碍,
这表明,了解这些过程的生物学与人类健康高度相关。纤毛
结构的复杂程度各不相同,这些形态决定了蛋白质的组成和组织
它们内部的信号分子。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尚不清楚。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,
尤其是对嗅觉提示的反应,人们知之甚少。线虫的感觉神经系统
是解决这些问题的理想模式。线虫个体化学感受性神经元展示
不同的纤毛形态,每种神经元类型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。和其他生物一样,线虫纤毛容纳了所有的嗅觉感受器和信号
分子。此外,嗅觉神经元纤毛的一个子集可以通过感觉活动来重塑。这些功能,
结合其遗传易操纵性和体内成像的适应性,提供了一个独特的机会
阐明塑造纤毛形态和功能的关键机制。这项提议将
系统地探索专门化纤毛形态如何有助于
线虫中的单个化学感觉神经元,并将通过以下方式确定细胞和分子机制
这些纤毛的形态被感官活动进一步改变。这项工作将为
了解化学感觉信号中纤毛相关缺陷的发病机制。所描述的实验
在这份提案中将为我提供宝贵的高分辨率显微技术培训,高分辨率定量
通过体内钙离子分析化学感觉行为和定量分析神经元功能
成像。此外,我的建议还包括具体的计划,以加强我在导师、网络和
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。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Alison Philbrook其他文献
Alison Philbrook的其他文献
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{{ truncateString('Alison Philbrook', 18)}}的其他基金
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:
10049182 - 财政年份:2019
- 资助金额:
$ 6.12万 - 项目类别:
Molecular regulation of nicotinic acetylcholine receptors
烟碱乙酰胆碱受体的分子调节
- 批准号:
9208128 - 财政年份:2015
- 资助金额:
$ 6.12万 - 项目类别:
Molecular regulation of nicotinic acetylcholine receptors
烟碱乙酰胆碱受体的分子调节
- 批准号:
8835674 - 财政年份:2015
- 资助金额:
$ 6.12万 - 项目类别:
Molecular regulation of nicotinic acetylcholine receptors
烟碱乙酰胆碱受体的分子调节
- 批准号:
9029173 - 财政年份:2015
- 资助金额:
$ 6.12万 - 项目类别:
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