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: 10047729
• 负责人: Kristin Engberg
• 金额: $ 31.29万
• 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/10047729
• 关键词: 3-Dimensional; Address; Anatomy; Animals; Attention; Automobile Driving; Axon; Back; Behavior; Brain; Categories; Cells; Chemistry; Collaborations; Communities; Complex; Consult; Cre driver; Data Set; Development; Doctor of Philosophy; 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 structure; 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; base; combinatorial; design; fluorophore; immunological status; insight; neural circuit; next generation; novel; optogenetics; promoter; real world application; recombinase; relating to nervous system; 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）