Protein Interaction Network Analysis to Test the Synaptic Hypothesis of Autism
蛋白质相互作用网络分析检验自闭症突触假说
基本信息
- 批准号:8616138
- 负责人:
- 金额:$ 9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-01-01 至 2015-12-31
- 项目状态:已结题
- 来源:
- 关键词:AchievementAntibodiesAntigen-Presenting CellsAutistic DisorderAwardBicucullineBiologicalBiological AssayBiological ProcessBiologyBrainBudgetsCellsCollectionDataData SetDevelopmentDiseaseExposure toFinancial compensationFlow CytometryGene Expression ProfileGenesGenomeGlutamatesGoalsHippocampus (Brain)HumanImageryImmunoprecipitationIn VitroIndividualKnowledgeLearningLinkLymphocyte antigenMapsMeasurementMeasuresMembraneMentorsMethodsMolecularMolecular BiologyMouse StrainsMusMutationNeuronsNeurotransmitter ReceptorPathway AnalysisPathway interactionsPhasePhysiologicalPropertyProtein-Protein Interaction MapProteinsProteomicsReportingResearchRisk FactorsSamplingScientistSignal TransductionSocial isolationStudentsSynapsesSystemT-LymphocyteTechnologyTestingTetrodotoxinTrainingTranslatingcareer developmentexperienceimmunogenicimmunological synapsein vivoinduced pluripotent stem celllink proteinnew technologynew therapeutic targetnovelnovel therapeuticsprogramsprotein complexprotein protein interactionpublic health relevanceresponserisk variantsignal processingtooltraffickingyeast two hybrid system
项目摘要
Project Summary/Abstract
"Evaluating the synaptic hypothesis of autism using protein-protein interaction network analysis"
Protein-protein interaction (PPI) networks of a cell are thought to represent a system with emergent network properties,
integrating signals for a variety of inputs into coordinated responses. A deeper understanding of protein complexes at the
synapse will enhance our knowledge of normal brain function and may highlight new therapeutic targets for diseases,
including autism. The applicant has recently developed a novel technology, multiplex immunoprecipitation measured by
flow cytometry (mIP-FCM) that allows the rapid, simultaneous, quantitative measurement of hundreds of protein-protein
interactions (PPIs) from small amounts of biological samples. This proposal involves translating mIP-FCM technology
to target synaptic proteins relevant to autism, and investigating the quantitative changes in protein complexes that
occur under physiological and disease-associated conditions. The observation of the dynamic activity of protein
complexes at the mouse and human glutamate synapse will contribute to a greater understanding of normal brain function,
and may highlight pathological molecular mechanisms of autism-associated genes.
The applicant proposes three specific aims: 1) Generate a multiplex IP-FCM assay targeted to synaptic proteins,
to be completed during year 1 of the K99 portion of the award; 2) Map synaptic PPIs in mice carrying autism-associated
mutations. This portion will be completed in years 2-5, during the K99/R00 transition. 3) Map synaptic PPIs in human
iPS neurons derived from autistic and typically developing individuals, to be completed during years 3-5 of the R00 phase
of the award. The overall goal of this proposal is to define specific changes in the PPI network of the glutamatergic
synapse associated with different autism risk factors, and to investigate the extent to which there is convergence of autism
risk genes into specific common molecular pathways at the synapse.
During the K99 phase of the award, the applicant will 1) Develop the mIP-FCM assay targeted to the
glutamatergic synapse, and learn appropriate statistical and visualization methods for the large datasets; 2) Learn to
manage a research team, including management of technical support staff and students, overseeing budgets, integrating
data from multiple individual projects, and acting as a mentor of junior scientists. The applicant has assembled a group of
experienced co-mentors to help with this career development training. Overall, this training will facilitate the
achievement of the applicant's long-term goal to develop an internationally-renowned independent research
program focused on the molecular mechanisms of autism risk factors.
项目总结/文摘
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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Stephen Edward Paucha Smith其他文献
Stephen Edward Paucha Smith的其他文献
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{{ truncateString('Stephen Edward Paucha Smith', 18)}}的其他基金
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定量蛋白质网络分析以改进 CAR 设计和功效
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- 资助金额:
$ 9万 - 项目类别:
Quantitative protein network profiling to improve CAR design and efficacy
定量蛋白质网络分析以改进 CAR 设计和功效
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10578701 - 财政年份:2020
- 资助金额:
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Subtyping the autisms using individualized protein network analysis
使用个体化蛋白质网络分析对自闭症进行亚型分类
- 批准号:
10212205 - 财政年份:2020
- 资助金额:
$ 9万 - 项目类别:
Purification of cell-type specific synaptic material using virally-expressed tags
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- 批准号:
9980828 - 财政年份:2019
- 资助金额:
$ 9万 - 项目类别:
Characterization of Autism Susceptibility Genes on Chromosome 15q11-13
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8145607 - 财政年份:2010
- 资助金额:
$ 9万 - 项目类别:
Characterization of Autism Susceptibility Genes on Chromosome 15q11-13
染色体 15q11-13 上自闭症易感基因的特征
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7912550 - 财政年份:2010
- 资助金额:
$ 9万 - 项目类别:
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