Learning principles from the pyrenoid, a phase-separated organelle
学习类核蛋白(一种相分离细胞器)的原理
基本信息
- 批准号:10544349
- 负责人:
- 金额:$ 50.44万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-01-01 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:ActivaseAlgaeAmyotrophic Lateral SclerosisArchitectureBackBindingBinding SitesBiochemical ProcessBiologicalBiological ModelsBiologyBiophysical ProcessCarbon DioxideCell physiologyCellsCellular StructuresChlamydomonasChlamydomonas reinhardtiiChloroplastsCollaborationsCouplingCryo-electron tomographyCuesDataDiseaseEnergy-Generating ResourcesEngineeringEnsureEnzymesEquilibriumExclusionExperimental ModelsFluorescence Recovery After PhotobleachingFree EnergyFunctional disorderGene ExpressionGenetic MaterialsHealthHoloenzymesImageIn VitroIndividualLearningLiquid substanceLocationMagicMalignant NeoplasmsMeasurementMediatingMembraneMetabolismMicroscopicModelingMolecularMultienzyme ComplexesMutationNatureOrganellesPhasePhysical condensationPhysiological ProcessesPositioning AttributeProcessPropertyProteinsRNARegulationRibosomesRibulose-Bisphosphate CarboxylaseRoleSignal TransductionSourceSpecificityStarchStructureSystemThylakoidsVariantVisualizationbiological adaptation to stressbiophysical modelcarbon fixationexperimental studyflexibilityhuman diseasein vivointerdisciplinary approachliquid dynamicsmodel organismmolecular dynamicsphysical propertyrecruitrepairedresponsesample fixationself assemblystoichiometrytheories
项目摘要
PROJECT ABSTRACT
Phase separation is an emerging organizing principle for intracellular biology. Processes that are now
understood to exploit phase separation include storage of genetic material, gene expression, ribosome
synthesis, signaling, stress response, and metabolism. While each phase-separating system has unique
features, there are universal themes relevant to all such systems, including regulation of the phase
boundary, the dynamics of mixing within and between condensates, and the interactions of condensates
with their surroundings. To uncover general principles regarding these common themes, we focus on a
well-suited model organism and system: the genetically tractable alga Chlamydomonas reinhardtii and
its pyrenoid, a non-membrane bound, phase-separated organelle responsible for efficient carbon fixation.
The pyrenoid offers many practical advantages: 1. its phase separation is driven by two well-
characterized components, the rigid enzyme complex Rubisco and the flexible linker protein EPYC1, via
a known specific binding interface; 2. the pyrenoid’s in vivo liquidity is reproduced in vitro with no energy
source; 3. in vivo assembly/disassembly is controllable by external cues; and 4. the pyrenoid is singular,
large, and stable enough to systematically investigate its functional interactions with other cellular
components. Based on these advantages, the pyrenoid has already proven to be a source of many
discoveries including the ability of a flexible multivalent linker to condense a rigid component, inheritance
of non-membrane bound organelles by fission, specific recruitment via a conserved binding motif, and a
magic-number effect. The key universal questions we will address with this system are: What is the role
of the valence, strength, and spacing of the interacting motifs in determining condensate properties? How
does the stability of small oligomers control phase boundaries? What keeps condensates in a liquid
state? How do cells control the number, size, and location of condensates, including their relation to other
cellular structures? Our approach will closely integrate theory and experiment, as providing fundamental
answers to these questions requires a multidisciplinary approach that places specific data within a broad
theoretical framework. We anticipate that our focus on underlying biophysical mechanisms will facilitate
generalizability of our results to a wide range of phase-separated intracellular systems.
项目摘要
相分离是细胞内生物学的一种新兴的组织原理。目前,
相分离的应用包括遗传物质的储存、基因表达、核糖体
合成、信号传导、应激反应和代谢。虽然每个相分离系统具有独特的
特征,存在与所有这些系统相关的普遍主题,包括阶段的调节
边界、凝析物内部和之间的混合动力学以及凝析物之间的相互作用
与周围环境的关系为了揭示关于这些共同主题的一般原则,我们将重点放在
非常适合的模式生物和系统:遗传上易处理的莱茵衣藻和
它的蛋白核,一种非膜结合的,相分离的细胞器,负责有效的碳固定。
蛋白核提供了许多实际的优点:1。它的相分离是由两个井驱动的-
特征性组分,刚性酶复合物Rubisco和柔性接头蛋白EPYC 1,通过
已知的特异性结合界面; 2.蛋白核在体内的流动性在体外不需要能量就能重现
来源; 3.体内组装/拆卸可通过外部线索控制;以及4.蛋白核是单一的,
足够大,足够稳定,可以系统地研究其与其他细胞的功能相互作用,
件.基于这些优点,蛋白核已经被证明是许多蛋白质的来源。
这些发现包括柔性多价接头缩合刚性组分的能力、遗传
非膜结合细胞器的分裂,通过保守的结合基序特异性募集,和
幻数效应我们将用这个系统解决的关键普遍问题是:
的价,强度和间距的相互作用的图案在确定冷凝物的性质?如何
小的低聚物的稳定性控制相界吗?是什么使冷凝物保持在液体中
州?细胞如何控制凝聚物的数量、大小和位置,包括它们与其他细胞的关系?
细胞结构?我们的方法将紧密结合理论和实验,为提供基本的
这些问题的答案需要一个多学科的方法,把具体的数据在一个广泛的
理论框架。我们预计,我们对潜在生物物理机制的关注将有助于
我们的结果的普遍性,以广泛的相分离的细胞内系统。
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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Martin Casimir Jonikas其他文献
Martin Casimir Jonikas的其他文献
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{{ truncateString('Martin Casimir Jonikas', 18)}}的其他基金
Learning principles from the pyrenoid, a phase-separated organelle
学习类核蛋白(一种相分离细胞器)的原理
- 批准号:
10322382 - 财政年份:2021
- 资助金额:
$ 50.44万 - 项目类别:
Transforming our understanding of eukaryotic gene functions through chemical genetics in the green alga Chlamydomonas reinhardtii
通过绿藻莱茵衣藻的化学遗传学改变我们对真核基因功能的理解
- 批准号:
9492909 - 财政年份:2015
- 资助金额:
$ 50.44万 - 项目类别:
Transforming our understanding of eukaryotic gene functions through chemical genetics in the green alga Chlamydomonas reinhardtii
通过绿藻莱茵衣藻的化学遗传学改变我们对真核基因功能的理解
- 批准号:
8955354 - 财政年份:2015
- 资助金额:
$ 50.44万 - 项目类别:
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