The Linchpin that Joins the Circadian Oscillator to Clock Output
The Linchpin that Joins the Circadian Oscillator to Clock Output
批准号:
10152597
负责人:
Andy LiWang
金额:
$32.64万
依托单位国家:
美国
项目类别:
财政年份:
2014
资助国家:
美国
项目状态:
已结题
起止时间:
2014-05-15 至 2023-04-30
关键词:
AnimalsApplications GrantsBacteriaBasic ScienceBehaviorBindingBinding ProteinsBinding SitesBiologicalBiological RhythmBiologyCellsCircadian RhythmsClock proteinComplexCyanobacteriumDNADNA BindingDataEventFaceGene ExpressionHeartIn VitroKnowledgeLengthLifeManuscriptsMapsMechanicsMediatingMetabolismMissionMolecularMotionNMR SpectroscopyOutputPathway interactionsPhasePhosphorylation SitePhosphotransferasesPhysiologyPlanet EarthPlantsProteinsReactionRegulationResearchResolutionRotationSasaScienceSignal TransductionSpectrum AnalysisStructureSystemTestingTimeUnited States National Institutes of HealthWorkactivating transcription factorcircadiancircadian pacemakerexperimental studyfungusinnovationinsightprotein complexprotein protein interactionreconstitutiontemporal measurementtranscription factortransmission process
中文摘要
项目摘要/摘要
好了!
许多生命形式,包括细菌、真菌、植物和动物,都在不知不觉中调节着它们的
预测日出和日落的新陈代谢、生理和行为。这些生理节律
节律产生于内源性的分子计时系统,称为生物钟,它
产生时钟组件的组装和拆卸的浪潮。未知是暂时的
以及这些短暂事件之间的因果关系,以及它们对时钟的重要性
功能。利旺实验室的目标是阐明这些
波是由昼夜节律振荡器通过时钟输出产生和传输的
转录因子-DNA结合节律的途径。方法是进行实时
完整重组的蓝藻生物钟的体外测量(6
蛋白质和DNA)在活细胞的环境之外。尽管有一套近乎完整的设备
蓝藻时钟蛋白复合体的高分辨结构(手稿正在审查中
在《科学》杂志上,这一系统的动力机制仍然不明。
因此,利旺实验室正在对重组蓝藻进行实时实验
生物钟反应来解开这个系统的动态计时机制。在目标1中,
利旺实验室将阐明短暂相互作用之间的时间和因果关系
分子水平上的事件,使用实时核磁共振波谱(核磁共振)。
时间信号从KaiABC振荡器传播时将被跟踪,通过
由Sasa和Cika蛋白介导的产生昼夜节律的拮抗输出途径
RpaA-DNA结合的节律。在目标2中,时间调节的信号传输网络
涉及KaiC(时钟的心脏)的特定残基的地图将从
KaIA结合位点的磷酸化(白天)以及Kaib和Sasa结合位点的磷酸化(夜间),
使用实时核磁共振。这两个目标的初步数据都证明了可行性。这项建议是
创新,因为这将是第一次可以观察到时间信号的涟漪
昼夜节律时钟蛋白的长度及其从一个时钟分量到
下一个,一个接一个的生理周期,实时的。这一提议意义重大,因为解决
时钟组件内部和之间的时间相互作用将揭示动态机制
它产生和传播时钟信号波,从而提供对
从静态结构中无法获得的生物计时。
英文摘要
PROJECT SUMMARY/ABSTRACT
!
Numerous life forms including bacteria, fungi, plants, and animals involuntarily regulate their
metabolism, physiology, and behavior in anticipation of sunrise and sunset. These circadian
rhythms arise from endogenous molecular timekeeping systems, called circadian clocks, which
generate waves of assembly and disassembly of clock components. Unknown are the temporal
and causal relationships between these transitory events, and how they are important to clock
function. The objective of the LiWang lab is to elucidate the dynamic mechanism by which these
waves are produced by and transmitted from the circadian oscillator, through clock-output
pathways, to transcription factor-DNA binding rhythms. The approach is to carry out real-time
measurements in vitro on the cyanobacterial circadian clock, reconstituted in its entirety (six
proteins and DNA) outside the milieu of live cells. Despite the availability of a near-complete set
of high-resolution structures of cyanobacterial clock protein complexes (manuscript under review
at Science, submitted on 06/04/16), the dynamic mechanism of this system remains obscure.
Thus, the LiWang lab is conducting real-time experiments on reconstituted cyanobacterial
circadian clock reactions to unravel the dynamic timekeeping mechanism of this system. In aim 1,
the LiWang lab will elucidate the temporal and causal relationships between transitory interaction
events at the molecular level, using real-time nuclear magnetic resonance spectroscopy (NMR).
Time signals will be followed as they propagate from the KaiABC oscillator, through the
antagonistic output pathways, mediated by SasA and CikA proteins, to generate circadian
rhythms of RpaA-DNA binding. In aim 2, the temporally regulated signal transmission network
involving specific residues across KaiC (the heart of the clock) will be mapped, from sites of
phosphorylation to the KaiA-binding sites (daytime) and KaiB- and SasA-binding sites (nighttime),
using real-time NMR. Preliminary data on both aims demonstrate feasibility. This proposal is
innovative, because for the first time, it will be possible to observe the rippling of time signals
across the lengths of circadian clock proteins and their transmission from one clock component to
the next, cycle after circadian cycle, in real time. This proposal is significant, because resolving
temporal interactions within and between clock components will reveal the dynamic machinery
that generates and propagates waves of clock signals, and thereby provide insights into
biological timekeeping that are unobtainable from static structures.
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DOI:
10.1126/science.abd4453
发表时间:
2021-10-08
期刊:
Science (New York, N.Y.)
影响因子:
--
作者:
[Chavan AG, Swan JA, Heisler J, Sancar C, Ernst DC, Fang M, Palacios JG, Spangler RK, Bagshaw CR, Tripathi S, Crosby P, Golden SS, Partch CL, LiWang A]
通讯作者:
LiWang A
DOI:
10.1016/j.jmb.2013.09.040
发表时间:
2014-01-23
期刊:
Journal of molecular biology
影响因子:
5.6
作者:
[Tseng R, Chang YG, Bravo I, Latham R, Chaudhary A, Kuo NW, Liwang A]
通讯作者:
Liwang A
DOI:
10.1093/icb/ict054
发表时间:
2013
期刊:
Integrative and comparative biology
影响因子:
2.6
作者:
[Chang,Yong-Gang, Tseng,Roger, Kuo,Nai-Wei, LiWang,Andy]
通讯作者:
LiWang,Andy
DOI:
10.1126/science.1260031
发表时间:
2015-07-17
期刊:
Science (New York, N.Y.)
影响因子:
--
作者:
[Chang YG, Cohen SE, Phong C, Myers WK, Kim YI, Tseng R, Lin J, Zhang L, Boyd JS, Lee Y, Kang S, Lee D, Li S, Britt RD, Rust MJ, Golden SS, LiWang A]
通讯作者:
LiWang A
DOI:
10.1126/science.aag2516
发表时间:
2017-03-17
期刊:
Science (New York, N.Y.)
影响因子:
--
作者:
[Tseng R, Goularte NF, Chavan A, Luu J, Cohen SE, Chang YG, Heisler J, Li S, Michael AK, Tripathi S, Golden SS, LiWang A, Partch CL]
通讯作者:
Partch CL
共 7 条
Temperature and metabolic compensation mechanisms in a circadian clock system
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批准号:10544006
-
项目类别:
-
资助金额:$37.85万
-
财政年份:2022
-
负责人:Andy LiWang
-
依托单位:
Temperature and metabolic compensation mechanisms in a circadian clock system
-
批准号:10594727
-
项目类别:
-
资助金额:$25.0万
-
财政年份:2022
-
负责人:Andy LiWang
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依托单位:
Temperature and metabolic compensation mechanisms in a circadian clock system
-
批准号:10797991
-
项目类别:
-
资助金额:$7.38万
-
财政年份:2022
-
负责人:Andy LiWang
-
依托单位:
Temperature and metabolic compensation mechanisms in a circadian clock system
-
批准号:10330682
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项目类别:
-
资助金额:$26.75万
-
财政年份:2022
-
负责人:Andy LiWang
-
依托单位:
The Linchpin that Joins the Circadian Oscillator to Clock Output
-
批准号:8846618
-
项目类别:
-
资助金额:$28.03万
-
财政年份:2014
-
负责人:Andy LiWang
-
依托单位:
Tertiary Structures of Circadian Clock Proteins by NMR
-
批准号:6719590
-
项目类别:
-
资助金额:$21.83万
-
财政年份:2002
-
负责人:Andy LiWang
-
依托单位:
The Structural and Biochemical Bases of Circadian Oscillator Rhythmicity
-
批准号:7677075
-
项目类别:
-
资助金额:$27.36万
-
财政年份:2002
-
负责人:Andy LiWang
-
依托单位:
Tertiary Structures of Circadian Clock Proteins by NMR
-
批准号:7048609
-
项目类别:
-
资助金额:$21.3万
-
财政年份:2002
-
负责人:Andy LiWang
-
依托单位:
Tertiary Structures of Circadian Clock Proteins by NMR
-
批准号:6868981
-
项目类别:
-
资助金额:$21.83万
-
财政年份:2002
-
负责人:Andy LiWang
-
依托单位:
Tertiary Structures of Circadian Clock Proteins by NMR
-
批准号:7636704
-
项目类别:
-
资助金额:$0.01万
-
财政年份:2002
-
负责人:Andy LiWang
-
依托单位:
Tertiary Structures of Circadian Clock Proteins by NMR
-
批准号:6419683
-
项目类别:
-
资助金额:$21.83万
-
财政年份:2002
-
负责人:Andy LiWang
-
依托单位:
Tertiary Structures of Circadian Clock Proteins by NMR
-
批准号:6620601
-
项目类别:
-
资助金额:$21.83万
-
财政年份:2002
-
负责人:Andy LiWang
-
依托单位:
QUANTITATION OF HYDROGEN BONDS OF DNA AND RNA BY NMR
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批准号:6181476
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项目类别:
-
资助金额:$10.08万
-
财政年份:1999
-
负责人:Andy LiWang
-
依托单位:
QUANTITATION OF HYDROGEN BONDS OF DNA AND RNA BY NMR
-
批准号:2728541
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项目类别:
-
资助金额:$10.08万
-
财政年份:1999
-
负责人:Andy LiWang
-
依托单位: