Recombinant Immunolabels for Nanoprecise Brain Mapping Across Scales
用于跨尺度纳米精确脑图谱的重组免疫标记
基本信息
- 批准号:10454277
- 负责人:
- 金额:$ 140.12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-30 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AffinityAntibodiesArchivesArray tomographyBRAIN initiativeBindingBiological AssayBrainBrain MappingCellsCollectionCryopreservationDNA SequenceEffectivenessEngineeringEnsureFreezingFunctional disorderFutureGoalsHigh-Throughput Nucleotide SequencingHumanHybridomasImageImage EnhancementImaging TechniquesIndividualLabelLeadMapsMethodsMicroscopyMolecularMonoclonal AntibodiesMusNeurosciencesNeurosciences ResearchPenetrationPlasmidsProteinsProxyReagentRecombinant AntibodyRecombinantsReproducibilityResearchResearch PersonnelResolutionResourcesSamplingStructureSubcellular structureSynapsesSystemTechniquesTissuesValidationWorkaffinity labelinganatomical tracingantibody engineeringbasebrain circuitrybrain tissuecell typecostimmunoreactivityimprovedinterestminiaturizenanobodiesnanometernanoscalenonhuman primatenovelopen sourceplasmid DNApreservationrepositoryscreeningsingle molecule
项目摘要
Recombinant Immunolabels for Nanoprecise Brain Mapping Across Scales
Understanding brain function and dysfunction requires an understanding of the circuitry of the brain from
molecules to cells to circuits. While no single technique can achieve this, a strategic combination of techniques
applied across scales can provide information that when integrated can lead to a more complete picture. These
techniques can range from analyses of single molecules, including their localization in nanodomains, to
subcellular compartments such as synapses and synaptic networks to entire brains.
One common theme of these techniques is that they require affinity probes that specifically label subcellular
structures, cell types, and circuits within the brain. We propose to enhance an existing resource of renewable
affinity probes in the form of an extensive collection of highly-validated monoclonal antibodies. We will enhance
our ongoing dissemination of low cost, high quality antibodies to neuroscience researchers by converting these
to recombinant form. This will also ensure permanence of this valuable collection of renewable reagents for
future researchers. We will use established methods to miniaturize these conventional antibodies into a
nanoscale form. These miniaturized antibodies will allow for labeling of brain targets with single nanometer
precision, which will provide more spatially precise labeling and overcome the limits to imaging resolution that
conventional Abs represent. Moreover, the miniaturized Abs will have much better sample penetration, allowing
for more efficient labeling of larger samples of the type used for defining intact circuits.
We have formed a consortium of experts who developed and/or are experts in a powerful set of advanced
techniques that together allow for brain mapping across scales. This consortium will validate nanoscale
antibodies in their respective techniques, a key component of rigor and reproducibility of any antibody-based
research. We will also generate and validate novel nanoscale antibodies against targets of great interest to brain
investigators for which no suitable reagents exist. Together, these efforts will further enhance the dissemination
of this valuable resource, and fundamentally accelerate the pace of brain circuit mapping across scales.
用于跨尺度纳米精确脑标测的重组免疫标记
了解大脑功能和功能障碍需要了解大脑的电路,
分子到细胞到电路虽然没有单一的技术可以做到这一点,一个战略性的技术组合,
跨尺度应用可提供信息,综合这些信息后可得出更全面的情况。这些
技术的范围可以从单个分子的分析,包括它们在纳米结构域中的定位,
亚细胞区室,如突触和突触网络到整个大脑。
这些技术的一个共同主题是,它们需要特异性标记亚细胞的亲和探针,
结构,细胞类型和大脑内的电路。我们建议加强现有的可再生能源,
亲和探针以高度验证的单克隆抗体的广泛集合的形式。我们将加强
我们正在向神经科学研究人员传播低成本,高质量的抗体,
重组形式。这也将确保这些宝贵的可再生试剂的永久性,
未来的研究者我们将使用已建立的方法将这些常规抗体纯化成
nanoscale形式。这些微型化的抗体将允许用单个纳米标记大脑靶点。
精度,这将提供更精确的空间标记,并克服成像分辨率的限制,
传统的ABS代表。此外,小型化的Ab将具有更好的样品渗透,
用于更有效地标记用于定义完整电路的类型的较大样本。
我们已经成立了一个专家联盟,他们开发了一套强大的先进的
这些技术一起允许跨尺度的大脑映射。该联盟将验证纳米级
抗体在其各自的技术,一个关键组成部分的严谨性和再现性的任何抗体为基础的
research.我们还将产生和验证针对大脑非常感兴趣的目标的新型纳米抗体
没有合适试剂的研究者。这些努力将进一步加强传播
这一宝贵的资源,并从根本上加快跨尺度脑回路映射的步伐。
项目成果
期刊论文数量(0)
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James S Trimmer其他文献
James S Trimmer的其他文献
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{{ truncateString('James S Trimmer', 18)}}的其他基金
Investigating the contributions of voltage gated sodium channels to oxaliplatin induced neuropathy
研究电压门控钠通道对奥沙利铂诱导的神经病变的影响
- 批准号:
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- 资助金额:
$ 140.12万 - 项目类别:
Defining the Proteomic Composition of ER:Plasma Membrane Junctions in Brain Neurons
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UC Davis/NIH NeuroMab Facility-Administrative Supplement
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9138371 - 财政年份:2015
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Genetically Encoded Reporters of Integrated Neural Activity for Functional Mapping of Neural Circuitry-Administrative Supplement
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