A new animal model to examine nervous system function, development, and regeneration
一种检查神经系统功能、发育和再生的新动物模型
基本信息
- 批准号:10312114
- 负责人:
- 金额:$ 12.53万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-12-15 至 2022-11-30
- 项目状态:已结题
- 来源:
- 关键词:AblationAction PotentialsAnimal BehaviorAnimal ModelAnimalsAxonBacteriaBehaviorBehavioralBehavioral MechanismsBiologicalBiological ModelsBiological ProcessBiologyBody partCellsClustered Regularly Interspaced Short Palindromic RepeatsCommunitiesComplexCuesDNADataDevelopmentDevelopmental ProcessDiseaseFoodFoundationsFutureGene Transfer TechniquesGeneticGenetic ModelsGenetic TechniquesGoalsGrantHealthHumanImageInjuryInvestigationJellyfishKnock-inKnock-outKnowledgeLeadLinkLongevityMapsMeasuresModelingModernizationMolecularNatural regenerationNerve RegenerationNervous System PhysiologyNervous system structureNeuronsNeuropeptidesNeurosciencesNuclear ImportNumeric Rating ScaleOpticsOral cavityOrganismPeptidesPharmaceutical PreparationsPhysiologyPopulationPositioning AttributePropertyPublishingRFamide peptideReagentRecoveryResearchResolutionRoleScienceSodiumStructureSystemSystems IntegrationTechniquesTestingTrainingTransgenic OrganismsVisionWhole OrganismWorkanalytical toolarginylphenylalaninamidebasecalcium indicatorcell motilitycell typehealingin vivoinnovationinsightmigrationmillisecondmolecular phenotypeneurodevelopmentneurogenesisneuromechanismneuroregulationnewborn neuronnoveloptogeneticsprogramsregeneration following injuryregenerativerelating to nervous systemsingle-cell RNA sequencingtheories
项目摘要
Model organisms have proven invaluable as more tractable systems to study fundamental principles of biology and by yielding breakthroughs that result from studying evolutionary innovations, for example, GFP, from jellyfish, or CRISPR, from bacteria. My goal is to leverage a new model system, developed during my postdoctoral work, that is uniquely positioned to provide insights of both types: Clytia hemisphaerica, a species of Mediterranean jellyfish. This proposal uses Clytia's distinctive features to identify precise mechanisms at the interface of neural development, neural regeneration, and systems neuroscience. First, Clytia are tiny (<1mm-1cm), transparent, and genetically tractable, making it possible to image and manipulate the activity of every neuron in the nervous system simultaneously, in vivo, using genetically encoded optical techniques. Further, Clytia numerically scale their nervous system at least an order of magnitude during their lifespan without disrupting system function, ending with more than ten thousand neurons. It is therefore also possible to observe continuous differentiation, migration, axon targeting, and functional activity simultaneously across the whole organism. Lastly, Clytia have poorly understood and powerful regenerative capabilities. These include the regeneration of large populations of genetically ablated neurons, with rapid recovery of the behaviors that those neurons control. These properties make Clytia an experimentally tractable platform to investigate: · Fundamental questions in systems neuroscience, including mechanisms underlying behaviors and behavior states, roles of neuromodulation, and approaches for studying system organization and function across scales. · Basic principles of neurodevelopment, particularly at the interface of development and function. · Mechanisms enabling regeneration and the seamless integration of new neurons into a functioning network. In Aim 1, I will characterize the molecular phenotypes of neurons and establish CRISPR-based knock-in to target effectors to specific subpopulations of cells. In Aim 2, I will use a coordinated behavior as my point of entry and develop and test models of underlying neural mechanisms. In Aim 3, I will examine how this behavioral system is robust to constant neurogenesis, and the mechanisms that enable its rapid recovery following genetic ablation of neurons. My vision is that, once the key foundational work has been completed and published, Clytia will become a widely used model system. This proposal serves as the first step, laying the foundation for my future independent program and for a Clytia community more broadly, and providing the essential training that I need to fill gaps in my knowledge, focusing on computational and single-cell RNA sequencing approaches.
模式生物已被证明是非常宝贵的,因为它是研究生物学基本原理的更易处理的系统,并通过研究进化创新而取得突破,例如水母的GFP或细菌的CRISPR。我的目标是利用一个新的模型系统,在我的博士后工作中开发的,这是独特的定位,以提供这两种类型的见解:Clytia hemisphaerica,一种地中海水母。 该提案使用Clytia的独特特征来确定神经发育,神经再生和系统神经科学界面的精确机制。首先,Clytia很小(<1 mm-1 cm),透明,遗传上易于处理,使得使用遗传编码光学技术在体内同时成像和操纵神经系统中每个神经元的活动成为可能。此外,Clytia在其生命周期内将其神经系统的数量级扩展至少一个数量级,而不会破坏系统功能,最终超过一万个神经元。因此,还可以在整个生物体中同时观察连续分化、迁移、轴突靶向和功能活性。最后,Clytia具有鲜为人知的强大再生能力。这些包括大量基因消融神经元的再生,以及这些神经元控制的行为的快速恢复。·系统神经科学中的基本问题,包括行为和行为状态的机制,神经调节的作用,以及研究系统组织和跨尺度功能的方法。 神经发育的基本原则,特别是在发育和功能的界面。 ·使再生和新神经元无缝整合到功能网络中的机制。在目标1中,我将描述神经元的分子表型,并建立基于CRISPR的基因敲入,将效应子靶向特定的细胞亚群。在目标2中,我将使用协调行为作为切入点,开发和测试潜在神经机制的模型。在目标3中,我将研究这种行为系统如何对持续的神经发生保持稳健,以及在神经元基因消融后使其快速恢复的机制。 我的愿景是,一旦关键的基础工作完成并发表,Clytia将成为一个广泛使用的模型系统。这个提议是第一步,为我未来的独立项目和更广泛的Clytia社区奠定了基础,并提供了必要的培训,我需要填补我的知识空白,专注于计算和单细胞RNA测序方法。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Brandon Weissbourd其他文献
Brandon Weissbourd的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Brandon Weissbourd', 18)}}的其他基金
A New Animal Model to Examine Nervous System Function Development and Regeneration
一种检查神经系统功能发育和再生的新动物模型
- 批准号:
10703706 - 财政年份:2020
- 资助金额:
$ 12.53万 - 项目类别:
相似海外基金
Kilohertz volumetric imaging of neuronal action potentials in awake behaving mice
清醒行为小鼠神经元动作电位的千赫兹体积成像
- 批准号:
10515267 - 财政年份:2022
- 资助金额:
$ 12.53万 - 项目类别:
Signal processing in horizontal cells of the mammalian retina – coding of visual information by calcium and sodium action potentials
哺乳动物视网膜水平细胞的信号处理 â 通过钙和钠动作电位编码视觉信息
- 批准号:
422915148 - 财政年份:2019
- 资助金额:
$ 12.53万 - 项目类别:
Research Grants
CAREER: Resolving action potentials and high-density neural signals from the surface of the brain
职业:解析来自大脑表面的动作电位和高密度神经信号
- 批准号:
1752274 - 财政年份:2018
- 资助金额:
$ 12.53万 - 项目类别:
Continuing Grant
Development of Nanosheet-Based Wireless Probes for Multi-Simultaneous Monitoring of Action Potentials and Neurotransmitters
开发基于纳米片的无线探针,用于同时监测动作电位和神经递质
- 批准号:
18H03539 - 财政年份:2018
- 资助金额:
$ 12.53万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Population Imaging of Action Potentials by Novel Two-Photon Microscopes and Genetically Encoded Voltage Indicators
通过新型双光子显微镜和基因编码电压指示器对动作电位进行群体成像
- 批准号:
9588470 - 财政年份:2018
- 资助金额:
$ 12.53万 - 项目类别:
Enhanced quantitative imaging of compound action potentials in multi-fascicular peripheral nerve with fast neural Electrical Impedance Tomography enabled by 3D multi-plane softening bioelectronics
通过 3D 多平面软化生物电子学实现快速神经电阻抗断层扫描,增强多束周围神经复合动作电位的定量成像
- 批准号:
10009724 - 财政年份:2018
- 资助金额:
$ 12.53万 - 项目类别:
Enhanced quantitative imaging of compound action potentials in multi-fascicular peripheral nerve with fast neural Electrical Impedance Tomography enabled by 3D multi-plane softening bioelectronics
通过 3D 多平面软化生物电子学实现快速神经电阻抗断层扫描,增强多束周围神经复合动作电位的定量成像
- 批准号:
10467225 - 财政年份:2018
- 资助金额:
$ 12.53万 - 项目类别:
Fast high-resolution deep photoacoustic tomography of action potentials in brains
大脑动作电位的快速高分辨率深度光声断层扫描
- 批准号:
9423398 - 财政年份:2017
- 资助金额:
$ 12.53万 - 项目类别:
NeuroGrid: a scalable system for large-scale recording of action potentials from the brain surface
NeuroGrid:用于大规模记录大脑表面动作电位的可扩展系统
- 批准号:
9357409 - 财政年份:2016
- 资助金额:
$ 12.53万 - 项目类别:
Noval regulatory mechanisms of axonal action potentials
轴突动作电位的新调节机制
- 批准号:
16K07006 - 财政年份:2016
- 资助金额:
$ 12.53万 - 项目类别:
Grant-in-Aid for Scientific Research (C)