Collaboration on preclinical autism cellular assays, biosignatures, and network analyses (Copacabana)

临床前自闭症细胞检测、生物特征和网络分析方面的合作(Copacabana)

基本信息

项目摘要

 DESCRIPTION (provided by applicant): This study aims to generate robust tools and workflows for creating human induced pluripotent stem cell (hIPSC)-based models of autism spectrum disorder (ASD), and to develop scalable assays for predictive molecular and cellular phenotypes relevant to autism. We have identified several key bottlenecks in the widespread adoption of hIPSCs as tools that allow the dissection of molecular mechanisms underlying neurological disease and enable preclinical drug screening. We have assembled a team of five leading experts in neuroscience, stem cell biology and computational biology, who will collaborate up with three innovation-driven biotech companies (Fluidigm, BD Biosciences and Synthetic Genomics) to overcome these roadblocks. Since autism is considered a disorder of synapse development and function that ultimately leads to circuit dysfunction in the brain, we will develop quantitative assays of synapse end network function that can be used in high-throughput drug screens. We also aim to uncover the upstream molecular events that precipitate synaptic and network dysregulation, and identify predictive RNA and protein signatures. Our strategy is to engineer models of genetic forms of autism by genomic manipulation using a well- characterized, neurotypical hIPSC line as the starting point. We will then differentiate these normal and mutant cells to cortical neurons and astrocytes, the two cell types that have been most strongly implicated in autism pathophysiology. Highly quantitative and sensitive assays at the single-cell level will be used to identify changes in protein and RNA expression that can distinguish ASD neurons and astrocytes from normal cells. Finally, we will develop assays measuring synapse density and strength using advanced technology that can be used in high-throughput format. We envision that our tools, technologies and assays, all of which we will make publicly available as they are being generated, will both critically contribute to our understanding of ASD and accelerate preclinical research of neurological disease.


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(1)

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Eugene Wei-Ming Yeo其他文献

Eugene Wei-Ming Yeo的其他文献

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{{ truncateString('Eugene Wei-Ming Yeo', 18)}}的其他基金

STAMP technology to enable single-cell and isoform-sensitive detection of RBP sites
STAMP 技术可实现 RBP 位点的单细胞和亚型敏感检测
  • 批准号:
    10277360
  • 财政年份:
    2021
  • 资助金额:
    $ 280.66万
  • 项目类别:
STAMP technology to enable single-cell and isoform-sensitive detection of RBP sites
STAMP 技术可实现 RBP 位点的单细胞和亚型敏感检测
  • 批准号:
    10475206
  • 财政年份:
    2021
  • 资助金额:
    $ 280.66万
  • 项目类别:
STAMP technology to enable single-cell and isoform-sensitive detection of RBP sites
STAMP 技术可实现 RBP 位点的单细胞和亚型敏感检测
  • 批准号:
    10632150
  • 财政年份:
    2021
  • 资助金额:
    $ 280.66万
  • 项目类别:
Single-Cell Transcriptomic and Epigenetics Core
单细胞转录组学和表观遗传学核心
  • 批准号:
    10214453
  • 财政年份:
    2018
  • 资助金额:
    $ 280.66万
  • 项目类别:
Single-Cell Transcriptomic and Epigenetics Core
单细胞转录组学和表观遗传学核心
  • 批准号:
    10453788
  • 财政年份:
    2018
  • 资助金额:
    $ 280.66万
  • 项目类别:
Defining the messenger RNP code in the brain
定义大脑中的信使 RNP 代码
  • 批准号:
    8997123
  • 财政年份:
    2012
  • 资助金额:
    $ 280.66万
  • 项目类别:
Defining the messenger RNP code in the brain
定义大脑中的信使 RNP 代码
  • 批准号:
    8295914
  • 财政年份:
    2012
  • 资助金额:
    $ 280.66万
  • 项目类别:
Defining the messenger RNP code in the brain
定义大脑中的信使 RNP 代码
  • 批准号:
    8427273
  • 财政年份:
    2012
  • 资助金额:
    $ 280.66万
  • 项目类别:
Defining the messenger RNP code in the brain
定义大脑中的信使 RNP 代码
  • 批准号:
    8605237
  • 财政年份:
    2012
  • 资助金额:
    $ 280.66万
  • 项目类别:
Defining the messenger RNP code in the brain
定义大脑中的信使 RNP 代码
  • 批准号:
    8790775
  • 财政年份:
    2012
  • 资助金额:
    $ 280.66万
  • 项目类别:

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Ascl1介导Wnt/beta-catenin通路在TLE海马硬化中反应性Astrocytes异常增生的作用及调控机制
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The contribution of astrocytes in behavioral flexibility
星形胶质细胞对行为灵活性的贡献
  • 批准号:
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  • 财政年份:
    2024
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阐明人星形胶质细胞中 APOE4 诱导的内溶酶体运输失调
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    2023
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DNA methylation signatures of Alzheimer's disease in aged astrocytes
老年星形胶质细胞中阿尔茨海默病的 DNA 甲基化特征
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    10807864
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    2023
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Genetically-Encoded, Non-Invasive and Wireless Modulation of Calcium Dynamics in Astrocytes With Spatiotemporal Precision and Depth
具有时空精度和深度的星形胶质细胞钙动态的基因编码、非侵入性无线调节
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Accelerating Functional Maturation of Human iPSC-Derived Astrocytes
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    10699505
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Defining cell type-specific functions for the selective autophagy receptor p62 in neurons and astrocytes
定义神经元和星形胶质细胞中选择性自噬受体 p62 的细胞类型特异性功能
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    2023
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    $ 280.66万
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Astrocytes control the termination of oligodendrocyte precursor cell perivascular migration during CNS development
星形胶质细胞控制中枢神经系统发育过程中少突胶质细胞前体细胞血管周围迁移的终止
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    10727537
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神经元和星形胶质细胞的多光谱成像:揭示健康和神经退行性疾病中的时空细胞器表型
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The role of lateral orbitofrontal cortex astrocytes in alcohol drinking
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Investigating the role of diazepam binding inhibitor (DBI) in astrocytes and neural circuit maturation
研究地西泮结合抑制剂 (DBI) 在星形胶质细胞和神经回路成熟中的作用
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