Quantitative studies of cell size control and homeostasis in bacteria
细菌细胞大小控制和稳态的定量研究
基本信息
- 批准号:9897538
- 负责人:
- 金额:$ 32.94万
- 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:2016-04-01 至 2021-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdolescenceAffectAgeAnimal ModelAutomobile DrivingBacillus subtilisBacteriaBirthCell CycleCell Cycle RegulationCell ProliferationCell SizeCell divisionCell modelCellsChildhoodChromosome 1ChromosomesClinicalCoupledDNADNA biosynthesisDevelopmentDiseaseEscherichia coliEvolutionGenesGeneticGenetic TechniquesGenomeGenome engineeringGrowthHomeostasisHumanImaging TechniquesInheritedLaboratoriesLifeLinkMalignant NeoplasmsMeasurementMeasuresMethodsMicrobiologyMicrofluidicsMitotic Cell CycleModelingModernizationMolecularMonitorOrganismPathologicPhysiologicalProcessProteinsProteomeReportingReproductionResearchRibosomesRoleSeriesStructureSystemTechniquesTestingTextbooksTimeUntranslated RNAcell growthdaughter cellinterdisciplinary approachpublic health relevancesingle molecule
项目摘要
DESCRIPTION (provided by applicant): How cells determine their size is unknown. A recently described "adder" model for cell size homeostasis transforms prior textbook models for cell size control (i.e. the "timer" and "sizer" models, which assumes cells actively monitor time between cell cycles or measure the absolute size of the cell, respectively). The adder model quantitatively spans over 1 billion years of evolutionary divergence to include both Gram‑negative Escherichia coli and Gram‑positive Bacillus subtilis. Therefore, any mechanism driving the quantity of mass added between cell divisions must be robust to the genetic, molecular, and physiologic difference between these species. The two candidates underlying the mechanism are the chromosome and the proteome (the set of all proteins in the cell), and it is important to understand how the two are coupled during growth. The genome is unique among cellular materials in that a single copy, essentially a single molecule, must be endowed to each descendent cell at division. The proteome must be composed so that the growth of the cell is optimized for a given growth condition and control of the cell cycle. The project employs multi‑disciplinary approach ranging from modern microbiological genetic techniques for genome engineering to high‑throughput measurements of the composition of the proteome, and connect them via quantitative modeling. More specifically, modern genetic recombineering techniques will be used to progressively increase the size of the E. coli chromosome with foreign, non‑coding DNA to double the native size of the chromosome. Using microfluidic and imaging techniques previously used to discover the adder principle, the mass added between divisions will be measured at the single--‐‑cell level to establish a direct correlative and causative lik between genome size and cell size. The proteome composition of the enlarged‑genome strains will be studied to unravel how the expression of a class of proteins for cellular reproduction differentially responds to various growth inhibitions. The proposed research will provide increased clarity of the mechanisms underlying cell size, the cell cycle and proliferation, one of the most basic processes critically and clinically important to human life.
描述(由申请人提供):细胞如何确定其大小尚不清楚。最近描述的用于细胞大小稳态的“加法器”模型转换了用于细胞大小控制的先前教科书模型(即,“计时器”和“尺寸器”模型,其分别假设细胞主动监测细胞周期之间的时间或测量细胞的绝对大小)。加法模型定量地跨越了超过10亿年的进化分歧,包括革兰氏阴性大肠杆菌和革兰氏阳性枯草芽孢杆菌。因此,任何驱动细胞分裂之间增加的质量的机制必须对这些物种之间的遗传、分子和生理差异具有鲁棒性。该机制的两个候选者是染色体和蛋白质组(细胞中所有蛋白质的集合),重要的是要了解两者在生长过程中是如何耦合的。基因组在细胞材料中是独特的,因为在分裂时必须赋予每个后代细胞一个拷贝,基本上是一个分子。蛋白质组的组成必须使细胞的生长对于给定的生长条件和细胞周期的控制是最优化的。该项目采用多学科方法,从用于基因组工程的现代微生物遗传技术到蛋白质组组成的高通量测量,并通过定量建模将它们连接起来。更具体地说,现代基因重组技术将用于逐步增加E.大肠杆菌染色体与外来的非编码DNA结合,使染色体的天然大小加倍。使用先前用于发现加法器原理的微流体和成像技术,将在单细胞水平上测量分裂之间添加的质量,以建立基因组大小和细胞大小之间的直接相关性和因果关系。将研究扩大基因组菌株的蛋白质组组成,以揭示一类用于细胞繁殖的蛋白质的表达如何对各种生长抑制做出差异性反应。拟议的研究将进一步阐明细胞大小、细胞周期和增殖的机制,这是对人类生命至关重要和临床重要的最基本过程之一。
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)
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Suckjoon Jun其他文献
Suckjoon Jun的其他文献
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{{ truncateString('Suckjoon Jun', 18)}}的其他基金
Control of cellular resource allocation across biological scales in microorganisms
微生物跨生物尺度的细胞资源分配控制
- 批准号:
10582366 - 财政年份:2021
- 资助金额:
$ 32.94万 - 项目类别:
Control of cellular resource allocation across biological scales in microorganisms
微生物跨生物尺度的细胞资源分配控制
- 批准号:
10415026 - 财政年份:2021
- 资助金额:
$ 32.94万 - 项目类别:
Control of cellular resource allocation across biological scales in microorganisms
微生物跨生物尺度的细胞资源分配控制
- 批准号:
10617797 - 财政年份:2021
- 资助金额:
$ 32.94万 - 项目类别:
Control of cellular resource allocation across biological scales in microorganisms
微生物跨生物尺度的细胞资源分配控制
- 批准号:
10810132 - 财政年份:2021
- 资助金额:
$ 32.94万 - 项目类别:
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