Center for Cell Circuits
细胞电路中心
基本信息
- 批准号:8688049
- 负责人:
- 金额:$ 294.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-07-09 至 2016-04-30
- 项目状态:已结题
- 来源:
- 关键词:Active LearningAcuteAddressAlgorithmsAutomobile DrivingBindingBiologicalBiological AssayCell CountCell physiologyCellsChromatinCommunitiesComplexComputational algorithmDataData SetDatabasesDendritic CellsDevelopmentDiagnosisDiseaseExperimental DesignsExplosionFunctional RNAGene ExpressionGene StructureGenesGenetic VariationGenome ComponentsGenomic DNAGenomicsImageryImmuneImmune responseInbred Strains MiceIndividualLearningMachine LearningMaintenanceMammalian CellMapsMeasurementMeasuresMediatingMessenger RNAMethodsModelingModificationMolecularMolecular GeneticsMolecular ProfilingMonitorMusNucleic AcidsOutputPhenotypePrincipal InvestigatorProteinsProtocols documentationRNARNA SplicingReagentRecombinantsResearchResearch PersonnelResolutionResourcesSamplingScientistTechnologyTestingTherapeutic InterventionTimeTranscriptVariantWorkbasecell typecomputer frameworkcostembryonic stem cellfrontiergene discoverygenetic profilinggenome sequencinggenome wide association studyhuman diseaseimprovedinnovationinterestpathogenreconstructionresearch studyresponsescreeningtool
项目摘要
DESCRIPTION (provided by applicant): Systematic reconstruction of genetic and molecular circuits in mammalian cells remains a significant, large-scale and unsolved challenge in genomics. The urgency to address it is underscored by the sizeable number of GWAS-derived disease genes whose functions remain largely obscure, limiting our progress towards biological understanding and therapeutic intervention. Recent advances in probing and manipulating cellular circuits on a genomic scale open the way for the development of a systematic method for circuit reconstruction. Here, we propose a Center for Cell Circuits to develop the reagents, technologies, algorithms, protocols and strategies needed to reconstruct molecular circuits. Our preliminary studies chart an initial path towards a universal strategy, which we will fully implement by developing a broad and integrated experimental and computational toolkit. We will develop methods for comprehensive profiling, genetic perturbations and mesoscale monitoring of diverse circuit layers (Aim 1). In parallel, we will develop a computational framework to analyze profiles, derive provisional models, use them to determine targets for perturbation and monitoring, and evaluate, refine and validate circuits based on those experiments (Aim 2). We will develop, test and refine this strategy in the context of two distinct and complementary mammalian circuits. First, we will produce an integrated, multi-layer circuit of the transcriptional response to pathogens in dendritic cells (Aim 3) as an example ofan acute environmental response. Second, we will reconstruct the the circuit of chromatin factors and non-coding RNAs that control chromatin organization and gene expression in mouse embryonic stem cells (Aim 4) as an example of the circuitry underlying stable cell states. These detailed datasets and models will reveal general principles of circuit organization, provide a resource for scientists in these two important fields, and allow computational biologists to test and develop algorithms. We will broadly disseminate our tools and methods to the community, enabling researchers to dissect any cell circuit of interest at unprecedented detail. Our work will open the way for reconstructing cellular circuits in human disease and individuals, to improve the accuracy of both diagnosis and treatment.
RELEVANCE: While it is now possible to rapidly identify genes that contribute to human disease, it is remains a major challenge to explain how these genes work together to carry out their normal functions or cause disease. We propose to develop a universal way to discover how genes work together in circuits, eventually leading to better diagnosis and therapy.
描述(由申请人提供):在哺乳动物细胞中系统地重建遗传和分子电路仍然是基因组学中一个重大的、大规模的和尚未解决的挑战。解决这一问题的紧迫性被大量的GWAS衍生疾病基因所突显,这些基因的功能在很大程度上仍然不清楚,限制了我们在生物学理解和治疗干预方面的进展。在基因组规模上探测和操纵细胞电路的最新进展为发展一种系统的电路重建方法开辟了道路。在这里,我们建议成立一个细胞电路中心,以开发重建分子电路所需的试剂、技术、算法、协议和策略。我们的初步研究描绘了一条通向普遍战略的初步道路,我们将通过开发一个广泛和综合的实验和计算工具包来充分实施这一战略。我们将开发对不同电路层进行全面剖析、遗传扰动和中尺度监测的方法(目标1)。同时,我们将开发一个计算框架来分析轮廓,推导临时模型,使用它们来确定扰动和监测的目标,并基于这些实验评估、改进和验证电路(目标2)。我们将在两个截然不同和互补的哺乳动物回路的背景下开发、测试和改进这一策略。首先,我们将在树突状细胞(目标3)中产生一个完整的、多层的对病原体的转录反应电路,作为急性环境反应的一个例子。其次,我们将重建小鼠胚胎干细胞中控制染色质组织和基因表达的染色质因子和非编码RNA的电路(AIM 4),作为稳定细胞状态的电路的一个例子。这些详细的数据集和模型将揭示电路组织的一般原则,为这两个重要领域的科学家提供资源,并允许计算生物学家测试和开发算法。我们将向社会广泛传播我们的工具和方法,使研究人员能够以前所未有的详细程度剖析任何感兴趣的细胞电路。我们的工作将为重建人类疾病和个人的细胞电路开辟道路,以提高诊断和治疗的准确性。
相关性:虽然现在可以快速识别导致人类疾病的基因,但解释这些基因如何协同工作来执行其正常功能或导致疾病仍然是一个重大挑战。我们建议开发一种通用的方法来发现基因如何在电路中协同工作,最终导致更好的诊断和治疗。
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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AVIV REGEV其他文献
AVIV REGEV的其他文献
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{{ truncateString('AVIV REGEV', 18)}}的其他基金
Core B: Data Management and Bioinformatics Core
核心 B:数据管理和生物信息学核心
- 批准号:
10207346 - 财政年份:2017
- 资助金额:
$ 294.18万 - 项目类别:
Clinical implementation of single cell tumor transcriptome analysis
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9035651 - 财政年份:2016
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DNA microscopy for spatially resolved genomic analyses in intact tissue
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- 批准号:
9360633 - 财政年份:2016
- 资助金额:
$ 294.18万 - 项目类别:
An integrated multiplexed genomic assay for low input clinical samples1
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9305830 - 财政年份:2015
- 资助金额:
$ 294.18万 - 项目类别:
Comprehensive Classification Of Neuronal Subtypes By Single Cell Transcriptomics
单细胞转录组学对神经元亚型的综合分类
- 批准号:
8822370 - 财政年份:2014
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$ 294.18万 - 项目类别:
Comprehensive Classification Of Neuronal Subtypes By Single Cell Transcriptomics
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- 批准号:
9324097 - 财政年份:2014
- 资助金额:
$ 294.18万 - 项目类别:
Trinity: Transcriptome assembly for genetic and functional analysis of cancer
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- 批准号:
8606947 - 财政年份:2013
- 资助金额:
$ 294.18万 - 项目类别:
Trinity: Transcriptome assembly for genetic and functional analysis of cancer
Trinity:用于癌症遗传和功能分析的转录组组装
- 批准号:
8735908 - 财政年份:2013
- 资助金额:
$ 294.18万 - 项目类别:
Trinity: Transcriptome assembly for genetic and functional analysis of cancer
Trinity:用于癌症遗传和功能分析的转录组组装
- 批准号:
9126450 - 财政年份:2013
- 资助金额:
$ 294.18万 - 项目类别:
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