Resource Core 1 - Primate/rodent Molecular Anatomy Core (PMAC)

资源核心 1 - 灵长类动物/啮齿动物分子解剖学核心 (PMAC)

• 批准号: 10687137
• 负责人: Kristin Engberg
• 金额: $ 32.86万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10687137
• 关键词: 3-Dimensional; Address; Anatomy; Animals; Attention; Automobile Driving; Axon; Back; Behavior; Brain; Categories; Cells; Chemistry; Collaborations; Communities; Complex; Cre driver; Data Analyses; Data Set; Development; Doctor of Philosophy; Educational process of instructing; Elements; Enhancers; Ensure; Gene Transfer Techniques; Generations; Genes; Genetic; Goals; Hydrogels; Individual; Label; Link; Mammals; Measures; Methods; Modernization; Molecular; Molecular Analysis; Molecular Profiling; Nature; Nervous System; Neurons; Neurosciences; Noise; Opsin; Optics; Paper; Pattern; Population; Primates; Property; Recording of previous events; Reporting; Resolution; Resources; Rodent; Running; Science; Signal Transduction; Specificity; Speed; Structure-Activity Relationship; System; Technology; Time; Tissues; Transgenic Organisms; Translating; Typology; Update; Viral; Viral Vector; Virus; Visualization; Work; combinatorial; data streams; design; fluorophore; immunological status; insight; neural; neural circuit; next generation; novel; optogenetics; promoter; real world application; recombinase; tool; transcriptomics

Resource Core 1 - Primate/rodent Molecular Anatomy Core (PMAC) Leads: Kristin Overton PhD and Karl Deisseroth MD PhD Summary The PMAC will develop, validate, and implement (in the real-world setting of the U19 team projects/collaborations), next-generation technologies for studying circuit structure-function relationships. The PMAC involves guided use and refinement of state-of-the-art molecular, viral, and anatomical strategies across projects, continuously adapted and modernized to keep up with (and drive) this fast-moving field over the course of the 5-year overall project. The PMAC will address key technologically-intensive questions that will continuously arise across projects as three main categories of primate-capable molecular and anatomical tool will be developed for the broader U19 team: 1) latest-generation hydrogel-based volume acquisition, registration, quantification, and analysis across species, including molecular analysis of the same cells with known activity patterns during behavior via IEG-based activity traces using two of our hydrogel-tissue chemistry methods (CLARITY and STARmap; 2) continuously-updated viral vectors for anatomy/activity visualization and causal control, precision-designed to take into account both animal history (including past virus exposure/immune status) and spectral overlap relevant to combinatorial usage of multiple optical tools together; and 3) versatile viral tools for tagging (with fluorescent and activity-sensing-or-control tools) circuit elements naturally used during specific behaviors, or for targeting cells based on many features of wiring, activity, and genetics. Aligning the functional (activity) features of cortical neurons with their genetic profiles is crucial. For the PMAC, we note the superb timing in that our recent development of STARmap (Wang et al. Science 2018) will allow addressing this issue in a general sense, assigning deep typology and rich molecular signature information (hundreds of genes, and even >1000 genes per cell) to the same individual neurons and ensembles observed to be naturally and causally involved in behavior. The PMAC will pay particular attention to integrative methods for crossing scales of observation, consulting with the DSC regarding effective means for storing and sending the massive datasets. Analysis of the datasets will be with methods developed by the computational RP3 and the DSC. Results from U19 teams in the course of implementation, relating to optical figures of merit, including signal-to- noise, aberrations, and speed, will be fed back to the PMAC in a tight closed-loop workflow guided by real-world application, a key opportunity for fundamental science itself.

资源核心1 -灵长类/啮齿动物分子解剖学核心（PMAC） 负责人：Kristin Overton博士和Karl Deisseroth博士 总结 PMAC将开发、验证和实施（在U19团队的真实环境中 项目/合作），用于研究电路结构-功能关系的下一代技术。的 PMAC涉及指导使用和完善最先进的分子，病毒和解剖策略， 项目，不断调整和现代化，以跟上（和驱动）这个快速发展的领域在整个过程中 5年总体项目的一部分。PMAC将解决关键的技术密集型问题， 作为灵长类动物分子和解剖工具的三个主要类别， 将为更广泛的U19团队开发：1）最新一代基于水凝胶的体积采集，配准， 跨物种定量和分析，包括对具有已知活性的相同细胞进行分子分析 使用我们的两种水凝胶-组织化学方法，通过基于IEG的活动轨迹， （MATERIITY和STARmap; 2）持续更新的病毒载体，用于解剖/活动可视化和因果关系分析 控制，精确度-设计考虑动物历史（包括过去的病毒暴露/免疫 状态）和光谱重叠;以及3）通用 用于标记（用荧光和活性感测或控制工具）天然使用的电路元件的病毒工具 在特定的行为过程中，或者基于布线、活动和遗传学的许多特征来靶向细胞。对准 皮质神经元的功能（活动）特征及其遗传特征是至关重要的。对于PMAC，我们注意到 我们最近开发的STARmap（Wang et al. Science 2018）的绝佳时机将允许解决 这个问题在一般意义上，分配深类型学和丰富的分子签名信息（数百个 基因，甚至每个细胞>1000个基因）到相同的个体神经元和集合体，观察到这些神经元和集合体是天然的。 并与行为有因果关系。PMAC将特别注意交叉的综合方法 观察尺度，与DSC协商关于储存和发送大量 数据集。数据集的分析将采用计算RP 3和DSC开发的方法。 U19小组在实施过程中取得的结果，涉及光学品质因数，包括信号- 噪声、像差和速度，将反馈到PMAC，在一个紧密的闭环工作流程中， 应用，基础科学本身的一个关键机会。