Quantitative Imaging and Modeling of Regulation by Bacterial Small RNA
细菌小 RNA 调节的定量成像和建模
基本信息
- 批准号:8991500
- 负责人:
- 金额:$ 28.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-01-01 至 2018-11-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectBacteriaBacterial GenesBase PairingBinding SitesBiochemicalBiochemical PathwayBioinformaticsCellsComplexComputer SimulationDataEquilibriumEscherichia coliGene ExpressionGene Expression ProfileGene Expression RegulationGene ProteinsGeneticGrowthHealthHigh-Throughput Nucleotide SequencingImageImage AnalysisImageryIndividualInvestigationKineticsLeadLightLocationMeasurementMediatingMediator of activation proteinMessenger RNAMetabolic PathwayMetabolismMethodsMicrobiologyModelingMolecularOutcomePhenotypePhysiologicalPlayPropertyRNA BindingRNA analysisRegulationRegulator GenesRegulonReportingResearchResolutionRoleSeriesShapesSmall RNAStressSugar PhosphatesSystemSystems BiologyTechniquesTimeTranslationsVariantVirulencebasebiological adaptation to stresscell growthcellular imaginggenome-widegenome-wide analysisimaging platformin vivointerestmRNA Transcript Degradationnovelpathogenic bacteriapreventquantitative imagingsingle moleculetranscriptomics
项目摘要
DESCRIPTION (provided by applicant): Bacterial small RNAs (here referred to as sRNAs) are important regulators for gene expression, especially those associated with stress responses and virulence. sRNAs function by base pairing with their target mRNAs and affecting their translation and stability. The ability of each sRNA to regulate multiple targets in its regulon creates a complex network for shaping gene expression and phenotype, which ultimately leads to global adaptation of bacteria. How do the kinetic properties of sRNA-mediated regulation establish an ordered pattern of gene expression? What is the global impact of sRNA-mediated regulation on bacterial phenotypes? These are two important fundamental questions yet to be addressed. In this proposal, we will tackle these questions. One of the bottlenecks so far that has precluded the building a complete model to describe sRNA regulatory networks is the lack of kinetic measurements inside bacterial cells. Therefore, we first propose to develop a super-resolution imaging and analysis platform allowing direct visualization and characterization of sRNA and target mRNAs at the single-cell level with single copy sensitivity. Applying this imaging and analysis platform to a model sRNA system, SgrS, in E. coli, we will fully dissect kinetic mechanisms of sRNA regulation on individual targets in Aim1, and further explore the molecular mechanism that governs the regulation selectivity among multiple targets in the regulon in Aim 2. In order to understand the global impact of sRNA regulation on the bacterial phenotype, in Aim 3, we will integrate high-throughput transcriptomic data and single cell imaging data with genome scale flux balance models of E. coli metabolism and identify differential metabolic pathway usage as a result of sRNA regulation. The proposed study by the combination of multi-level experimental characterization and computational simulation will provide the most systematic description of sRNA regulation to date and will establish a novel framework for sRNA analysis that can be generalized to other bacterial and eukaryotic sRNAs.
描述(由申请人提供):细菌小RNA(此处称为sRNA)是基因表达的重要调节因子,尤其是与应激反应和毒力相关的那些。sRNA通过与其靶mRNA的碱基配对发挥作用,并影响其翻译和稳定性。每个sRNA在其调节子中调节多个靶点的能力创建了一个复杂的网络,用于塑造基因表达和表型,最终导致细菌的全局适应。sRNA介导调控的动力学特性如何建立基因表达的有序模式?sRNA介导的调控对细菌表型的全球影响是什么?这是两个尚待解决的重要基本问题。在本提案中,我们将解决这些问题。到目前为止,阻碍建立一个完整的模型来描述sRNA调控网络的瓶颈之一是缺乏细菌细胞内的动力学测量。因此,我们首先提出开发一种超分辨率成像和分析平台,允许在单细胞水平上以单拷贝灵敏度直接可视化和表征sRNA和靶mRNA。将该成像分析平台应用于E. coli中,我们将充分剖析Aim 1中单个靶点上sRNA调控的动力学机制,并进一步探索Aim 2中调节子中多个靶点之间调控选择性的分子机制。为了了解sRNA调控对细菌表型的整体影响,在目标3中,我们将整合高通量转录组数据和单细胞成像数据与E.大肠杆菌代谢,并确定差异代谢途径的使用作为sRNA调节的结果。多层次的实验表征和计算模拟相结合的研究将提供迄今为止最系统的sRNA调控描述,并将建立一个新的sRNA分析框架,可以推广到其他细菌和真核sRNA。
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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Taekjip Ha其他文献
Taekjip Ha的其他文献
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{{ truncateString('Taekjip Ha', 18)}}的其他基金
Chromatin Function During Transcription and DNA Repair at Single Molecule Resolutionin Living Cells
活细胞中单分子分辨率转录和 DNA 修复过程中的染色质功能
- 批准号:
10264097 - 财政年份:2020
- 资助金额:
$ 28.56万 - 项目类别:
Chromatin Function During Transcription and DNA Repair at Single Molecule Resolutionin Living Cells
活细胞中单分子分辨率转录和 DNA 修复过程中的染色质功能
- 批准号:
10687212 - 财政年份:2020
- 资助金额:
$ 28.56万 - 项目类别:
Chromatin Function During Transcription and DNA Repair at Single Molecule Resolutionin Living Cells
活细胞中单分子分辨率转录和 DNA 修复过程中的染色质功能
- 批准号:
10456263 - 财政年份:2020
- 资助金额:
$ 28.56万 - 项目类别:
Single Molecule Studies of Nucleic Acids Remodeling
核酸重塑的单分子研究
- 批准号:
10152600 - 财政年份:2017
- 资助金额:
$ 28.56万 - 项目类别:
Single Molecule Studies of Nucleic Acids Remodeling
核酸重塑的单分子研究
- 批准号:
9924561 - 财政年份:2017
- 资助金额:
$ 28.56万 - 项目类别:
Single molecule and biophysical studies of nucleic acid remodeling
核酸重塑的单分子和生物物理研究
- 批准号:
10864190 - 财政年份:2017
- 资助金额:
$ 28.56万 - 项目类别:
Single molecule and biophysical studies of nucleic acid remodeling
核酸重塑的单分子和生物物理研究
- 批准号:
10414234 - 财政年份:2017
- 资助金额:
$ 28.56万 - 项目类别:
Quantitative Imaging and Modeling of Regulation by Bacterial Small RNA
细菌小 RNA 调节的定量成像和建模
- 批准号:
9196362 - 财政年份:2015
- 资助金额:
$ 28.56万 - 项目类别:
Single-molecule and super-resolution studies of RIG-I pathways
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- 批准号:
7746262 - 财政年份:2009
- 资助金额:
$ 28.56万 - 项目类别:
2008 Single Molecule Approaches to Biology Gordon Research Conference
2008 年单分子生物学方法戈登研究会议
- 批准号:
7482778 - 财政年份:2008
- 资助金额:
$ 28.56万 - 项目类别:
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