Molecular and cellular mechanisms of circadian timekeeping in a prokaryote model
原核生物模型中昼夜节律的分子和细胞机制
基本信息
- 批准号:10386091
- 负责人:
- 金额:$ 3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-04-04 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAnacystisnidulansAnimal ModelAnimalsBar CodesBindingBiochemicalBiologicalBiological AssayBiological ClocksBiological ModelsBiological RhythmBiotechnologyCardiovascular DiseasesCell physiologyCellsCircadian DysregulationCircadian RhythmsClock proteinComplexCryo-electron tomographyCuesCyanobacteriumCytologyDiseaseEnvironmentEscherichia coliEukaryotaEventFunctional disorderGenesGeneticGenomicsGrowthHealthHumanIn VitroIonsLibrariesMalignant NeoplasmsMammalsMediatingMental disordersMetabolicMetabolic syndromeMetabolismModelingMolecularNucleotidesOrganismPersonal SatisfactionPhasePhenotypePhosphotransferasesPhylogenetic AnalysisPhysiologicalPhysiologyPreparationProductionProkaryotic CellsPropertyProtein BiochemistryProteinsRegulationResolutionSasaSignal TransductionSiteSleep DisordersSystemTimeTreesWorkcircadiancircadian pacemakerexperimental studyfitnesshuman pathogenpromoterreconstitutiontranscription factor
项目摘要
This project leverages a cyanobacterial model system to answer the following questions: what are the molecular
interactions that mark the passage of time in a cell, where do they occur in the cell, how do they mediate temporal
regulation of events, and why does biological timing matter for fitness? The circadian biological clock is an
oscillatory timer that drives 24-h rhythms of biological activities. Clock dysfunction in humans is related to a
spectrum of health conditions such as cardiovascular disease, cancer, metabolic syndrome, mental illness, and
sleep disorders. However, the circadian clock is pervasive well beyond mammals, promoting fitness in diverse
organisms throughout the phylogenetic tree. The circadian clock of the cyanobacterium Synechococcus
elongatus generates bona fide circadian rhythms of genetic, physiological, and metabolic activities that fulfill all
criteria that define circadian clocks in eukaryotes. In this genetically tractable model organism it is possible to
systematically alter the physical and biochemical properties of clock proteins and trace the impact of these
changes from their proximal effects, through the protein-interaction network, to the expressed circadian
phenotype. A new in vitro preparation comprising the oscillator proteins KaiA, KaiB, and KaiC, along with the
kinases CikA and SasA and the transcription factor RpaA, reconstitutes the circadian rhythm of binding of RpaA
to its target promoter with a real-time readout. This project will apply the in vitro clock and other technical and
conceptual advances towards biochemical, cytological, genomic, and physiological objectives that will answer
the target questions. The in vitro clock will reveal the molecular events that occur when the clock resets to an
environmental timing cue, identify the sites of action of nucleotides that modulate the timing circuit, and determine
how RpaA and a second transcription factor that is regulated by environmental signals, RpaB, work together to
influence circadian phasing. The discovery that the kinases SasA and CikA impart tolerance to fluctuating
oscillator component concentrations will overcome past hurdles for establishing a circadian circuit in Escherichia
coli as a naïve model system for exploring clock connections to cellular physiology and for biotechnology
applications. High-resolution cryo-electron tomography and focused ion-beam milling will be used to visualize
clock-controlled daily changes in intracellular organization and the clock complex itself. The molecular basis and
fitness advantage of circadian control of natural transformation will be determined. A bar-coded transposon
library first used to identify all genes required for photoautotrophic growth will be used to identify new loci that
contribute to fitness in a day-night cycle. Paired with physiological and metabolic assays, these experiments will
answer the question: why does the timing of molecular events matter? Together, these approaches will elucidate
clock mechanisms and the value of the clock to diurnal physiology, and will advance biotechnological
opportunities for controlling metabolism in both photosynthetic and traditional bacterial production systems.
该项目利用蓝藻模型系统来回答以下问题:分子是什么?
标记细胞中时间流逝的相互作用,它们发生在细胞中的何处,它们如何介导时间
事件的调节,为什么生物钟对健身很重要?
驱动人类生物活动 24 小时节律的振荡计时器与生物钟功能障碍有关。
一系列健康状况,如心血管疾病、癌症、代谢综合征、精神疾病和
然而,生物钟在哺乳动物之外也很普遍,它可以促进多种动物的健康。
整个系统发育树中的生物体 蓝藻聚球藻的生物钟。
elongatus 产生真正的遗传、生理和代谢活动的昼夜节律,以满足所有需要
定义真核生物生物钟的标准在这种遗传上易于处理的模型生物中,有可能
系统地改变时钟蛋白的物理和生化特性并追踪这些影响
从它们的近端效应,通过蛋白质相互作用网络,到表达的昼夜节律的变化
一种新的体外制剂,包含振荡器蛋白 KaiA、KaiB 和 KaiC,以及
激酶 CikA 和 SasA 以及转录因子 RpaA,重建 RpaA 结合的昼夜节律
其目标启动子具有实时读数,该项目将应用体外时钟和其他技术和技术。
生化、细胞学、基因组学和生理学目标的概念进展将回答
体外时钟将揭示当时钟重置到某个值时发生的分子事件。
环境计时线索,识别调节计时电路的核苷酸的作用位点,并确定
RpaA 和受环境信号调节的第二种转录因子 RpaB 如何共同作用
影响昼夜节律的发现是,激酶 SasA 和 CikA 赋予波动耐受性。
振荡器成分浓度将克服过去在大肠杆菌中建立昼夜节律回路的障碍
大肠杆菌作为一个简单的模型系统,用于探索时钟与细胞生理学和生物技术的联系
高分辨率冷冻电子断层扫描和聚焦离子束铣削将用于可视化。
细胞内组织和时钟复合物本身的时钟控制的日常变化。
自然转化的昼夜节律控制的适应性优势将被确定。
首先用于识别光自养生长所需的所有基因的文库将用于识别新的基因座
这些实验与生理和代谢测定相结合,有助于昼夜循环的健康。
回答这个问题:为什么分子事件的时间很重要?这些方法将共同阐明
时钟机制和时钟对昼夜生理学的价值,并将推进生物技术
控制光合作用和传统细菌生产系统中新陈代谢的机会。
项目成果
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{{ truncateString('SUSAN S GOLDEN', 18)}}的其他基金
Molecular and cellular mechanisms of circadian timekeeping in a prokaryote model
原核生物模型中昼夜节律的分子和细胞机制
- 批准号:
9253415 - 财政年份:2016
- 资助金额:
$ 3万 - 项目类别:
Molecular and cellular mechanisms of circadian timekeeping in a prokaryote model
原核生物模型中昼夜节律的分子和细胞机制
- 批准号:
9900016 - 财政年份:2016
- 资助金额:
$ 3万 - 项目类别:
Molecular and cellular mechanisms of circadian timekeeping in a prokaryote model
原核生物模型中昼夜节律的分子和细胞机制
- 批准号:
9076109 - 财政年份:2016
- 资助金额:
$ 3万 - 项目类别:
Molecular and cellular mechanisms of circadian timekeeping in a prokaryote model
原核生物模型中昼夜节律的分子和细胞机制
- 批准号:
10380893 - 财政年份:2016
- 资助金额:
$ 3万 - 项目类别:
Undergraduate Summer Research Experience: Molecular and cellular mechanisms of circadian timekeeping in a prokaryote model
本科暑期研究经历:原核生物模型中昼夜节律的分子和细胞机制
- 批准号:
10810593 - 财政年份:2016
- 资助金额:
$ 3万 - 项目类别:
Molecular and cellular mechanisms of circadian timekeeping in a prokaryote model
原核生物模型中昼夜节律的分子和细胞机制
- 批准号:
10201243 - 财政年份:2016
- 资助金额:
$ 3万 - 项目类别:
Admin. Supplement for Equipment: Molecular and cellular mechanisms of circadian timekeeping in a prokaryote model
行政。
- 批准号:
10811051 - 财政年份:2016
- 资助金额:
$ 3万 - 项目类别:
Molecular and cellular mechanisms of circadian timekeeping in a prokaryote model
原核生物模型中昼夜节律的分子和细胞机制
- 批准号:
10582345 - 财政年份:2016
- 资助金额:
$ 3万 - 项目类别:
Molecular and cellular mechanisms of circadian timekeeping in a prokaryote model
原核生物模型中昼夜节律的分子和细胞机制
- 批准号:
10592430 - 财政年份:2016
- 资助金额:
$ 3万 - 项目类别:
4th ASM Conference on Prokaryotic Cell Biology and Development
第四届 ASM 原核细胞生物学与发育会议
- 批准号:
8319208 - 财政年份:2012
- 资助金额:
$ 3万 - 项目类别:
相似海外基金
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- 资助金额:
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Molecular and cellular mechanisms of circadian timekeeping in a prokaryote model
原核生物模型中昼夜节律的分子和细胞机制
- 批准号:
10380893 - 财政年份:2016
- 资助金额:
$ 3万 - 项目类别:
Molecular and cellular mechanisms of circadian timekeeping in a prokaryote model
原核生物模型中昼夜节律的分子和细胞机制
- 批准号:
10201243 - 财政年份:2016
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