High Throughput Methods for Single Cell Proteomics
单细胞蛋白质组学的高通量方法
基本信息
- 批准号:10609071
- 负责人:
- 金额:$ 22.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAction PotentialsAdsorptionAlzheimer&aposs DiseaseBiochemicalBrainBrain DiseasesCardiac MyocytesCell SizeCell physiologyCellsDNA Sequence AlterationDiseaseElectric CapacitanceElectrodesElectrophysiology (science)EnvironmentGene ExpressionGenesGeneticGenotypeGoalsIn SituIndividualMass Spectrum AnalysisMeasurementMeasuresMembrane PotentialsMental DepressionMethodsMolecularMuscle FibersMutationNeuronsNeuropeptidesOrganoidsOutcomePatch-Clamp TechniquesPathway interactionsPatientsPhenotypePost-Translational Protein ProcessingPotassiumProtein BiosynthesisProteinsProteomeProteomicsProtocols documentationResearchRestSamplingSchizophreniaSignal TransductionSkinSodiumStructure of beta Cell of isletTechniquesautism spectrum disordercell typedrug actionexcitatory neuronexperimental studyhuman diseaseimprovedinhibitory neuronmass spectrometermolecular phenotypenanolitrenervous system disorderneuronal circuitryneurotransmitter releasepatch clamppressureprogramsprotein expressionproteostasissingle cell analysistranscriptome sequencing
项目摘要
PROJECT SUMMARY/ ABSTRACT
To understand deviations in normal function of neurons and neuronal circuits brought on by disease, we
will develop methods using patch clamping to measure the electrophysiology of individual neurons and
then use mass spectrometry-based proteomics to measure the proteome. Now that neurons can be
created from the skin cells of patients harboring disease genes to determine genotype to phenotype
relationships between the genetic defects and electrophysiology, the methods we develop have great
potential to significantly improve our ability to study human diseases of the brain. “Brain” organoids are
also being created from skin cells to recapitulate a 3-dimensional environment for neurons and to include
excitatory and inhibitory neurons. The ability to concurrently measure electrophysiology and protein
expression will allow a determination of how disease related perturbations to neurons and other cells are
related to molecular phenotypes. Single cell RNA-SEQ is used to measure gene expression in neurons,
but gene expression profiles fail to account for rates of protein synthesis, degradation, proteostasis, post
translational modification and enzymatic activity, all of which are critical cellular functions accomplished
by proteins. Single cell mass spectrometry has been applied to neurons to measure metabolites and
neuropeptides, but efforts to measure the proteome have lagged. We have established that proteins can
be measured in neurons after electrophysiology, but here we propose to greatly increase the scale of
measurements as well as the throughput. These methods will be broadly applicable as patch clamping
techniques is a widely used technique to measure ionic currents in a variety of cell types including
neurons, cardiomyocytes, muscle fibers and pancreatic beta cells. Furthermore, these methods will
enable experiments to determine the mechanism of action of drugs that restore normal electrophysiology
to neurons
项目摘要/摘要
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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John R Yates III其他文献
John R Yates III的其他文献
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{{ truncateString('John R Yates III', 18)}}的其他基金
Analysis of protein interactions in neurodegenerative disease
神经退行性疾病中蛋白质相互作用的分析
- 批准号:
10613978 - 财政年份:2022
- 资助金额:
$ 22.63万 - 项目类别:
High Throughput Methods for Single Cell Proteomics
单细胞蛋白质组学的高通量方法
- 批准号:
10433158 - 财政年份:2022
- 资助金额:
$ 22.63万 - 项目类别:
Measurement of Aberrant Protein Folds in Malignant Cells with Proteomics and Mass Spectrometry
用蛋白质组学和质谱法测量恶性肿瘤细胞中的异常蛋白质折叠
- 批准号:
9233438 - 财政年份:2017
- 资助金额:
$ 22.63万 - 项目类别:
Pulse-Chase Labeling with 15N and AHA in an Alzheimer's Mouse Model
在阿尔茨海默病小鼠模型中使用 15N 和 AHA 进行脉冲追踪标记
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9107688 - 财政年份:2015
- 资助金额:
$ 22.63万 - 项目类别:
Pulse-Chase Labeling with 15N and AHA in an Alzheimer's Mouse Model
在阿尔茨海默病小鼠模型中使用 15N 和 AHA 进行脉冲追踪标记
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8919211 - 财政年份:2014
- 资助金额:
$ 22.63万 - 项目类别:
Pulse-Chase Labeling with 15N and AHA in an Alzheimer's Mouse Model
在阿尔茨海默病小鼠模型中使用 15N 和 AHA 进行脉冲追踪标记
- 批准号:
8749039 - 财政年份:2014
- 资助金额:
$ 22.63万 - 项目类别:
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