Determine how protein synthesis is regulated during cell growth and division
确定细胞生长和分裂过程中蛋白质合成的调节方式
基本信息
- 批准号:10700156
- 负责人:
- 金额:$ 12.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-07 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:Abnormal CellAddressAffectB-LymphocytesBackBiogenesisBiologyCell CountCell CycleCell Cycle ProgressionCell Cycle RegulationCell Cycle StageCell MaintenanceCell ProliferationCell SizeCell divisionCell physiologyCellsCellular biologyComplexCyclin-Dependent KinasesCyclinsDataDevelopmentDevelopmental BiologyDiseaseEquilibriumFeedbackFeedsFoundationsG1/S TransitionGrowthHomeostasisHumanHyperplasiaHypertrophyImpairmentInvestigationKnowledgeLawsLinkLiverMalignant NeoplasmsMammalian CellMass Spectrum AnalysisMeasuresMediatingMentorsMessenger RNAMolecularMolecular BiologyNatural regenerationPathologicPhasePhysiologicalProcessPropertyProtein BiosynthesisProteomeRB1 geneRNA-Binding ProteinsRegulationResearchRetinoblastoma ProteinRibosomal ProteinsRibosomal RNARibosomesS phaseTechnologyTestingTissuesTrainingTraining ProgramsTransfer RNATranslational RegulationTranslationsWorkcareercareer developmentcell growthcell growth regulationhealingin vivo Modelinhibitorinsightlive cell imagingliver cell proliferationrate of changeskill acquisitiontissue regenerationtumorigenesis
项目摘要
Project Summary/Abstract
Cell growth and division are the essential processes for tissue homeostasis, regeneration, and cancer
development. Therefore, the study of cell growth regulation is important for understanding impaired tissue
regeneration and tumorigenesis.
Cell growth and cell division are coordinated via mutual regulation, and these two processes together
determine a fundamental cellular property, the cell size. The molecular mechanisms underlying the linkages
between these processes are largely unknown. Cell growth can trigger cell division by diluting the cell cycle
inhibitor RB, which contributes to the maintenance of cell size homeostasis. The RB dilution mechanism relies
on the cell cycle-dependent synthesis of RB protein, but the mechanism regulating RB synthesis is still unclear.
On the other hand, cell cycle and cell size can feed back to regulate cell growth rate, of which the mechanisms
are yet unknown. I found that the protein synthesis efficiency, a major determinant of cell growth efficiency,
increases at the G1/S transition and decreases as cells grow larger within each cell cycle phase, suggesting that
the global protein synthesis rate is actively regulated to facilitate cell cycle progression and cell size control .
Crucially, both RB1 mRNA and total mRNA concentrations are not cell cycle-dependent, implying previously
unknown translational mechanisms.
Here, in this proposal, I aim to address these gaps in our knowledge by determining the molecular
mechanisms regulating RB synthesis and global protein synthesis during cell cycle progression and cell growth.
The investigation of RB protein synthesis during cell cycle progression (Aim1) will further reveal the molecular
basis of how cell growth triggers cell division, and the study on global protein synthesis during cell cycle
progression (Aim2) will help us understand how cell cycle regulates cell growth. These two aims link cell growth
with cell division from the perspective of protein synthesis regulation. Then, the study on how protein synthesis
is regulated during cell growth (Aim3) explores the mechanism of how cell size feeds back to regulate growth
rate. Thus, the three aims together set up a foundation towards a deeper understanding of the principles
governing cell growth and proliferation.
The completion of above aims will deepen our understanding of the fundamental molecular mechanisms
regulating protein synthesis and cell growth rate, and therefore have broad impacts on cell and developmental
biology. Moreover, this work will enhance our understanding of tissue regeneration deficiencies and
tumorigenesis. With the help of an outstanding team of mentors, collaborators, and consultants, I will train in the
cutting-edge technologies in quantitative biology and molecular biology, and acquire skills for my career
development. Together, the proposed scientific and training program form a strong foundation for an independent
research career in understanding the principles of cell growth under physiological and pathological conditions.
项目摘要/摘要
细胞生长和分裂是组织动态平衡、再生和癌症的基本过程。
发展。因此,研究细胞生长调控对于了解受损组织具有重要意义。
再生和肿瘤发生。
细胞的生长和分裂是通过相互调节来协调的,这两个过程共同作用
确定一个基本的细胞属性,细胞大小。这些联系背后的分子机制
这些过程之间的关系在很大程度上是未知的。细胞生长可以通过稀释细胞周期来触发细胞分裂
抑制剂Rb,有助于维持细胞大小的动态平衡。Rb稀释机制依赖于
Rb蛋白的合成依赖于细胞周期,但调控Rb蛋白合成的机制尚不清楚。
另一方面,细胞周期和细胞大小可以反馈调节细胞的生长速度,其机制
都是未知的。我发现蛋白质合成效率是细胞生长效率的主要决定因素,
在G1/S转变时增加,并在每个细胞周期阶段随着细胞变大而减少,这表明
全球蛋白质合成速率被主动调节,以促进细胞周期进展和细胞大小控制。
重要的是,rb1mrna和总mrna浓度都不依赖于细胞周期,这意味着以前
未知的翻译机制。
在这里,在这项提议中,我的目标是通过确定分子,来解决我们知识中的这些差距
细胞周期进程和细胞生长过程中调节Rb合成和全球蛋白质合成的机制。
对细胞周期进程中Rb蛋白合成的研究(Aim1)将进一步揭示
细胞生长如何触发细胞分裂的基础,以及细胞周期中全球蛋白质合成的研究
AIM2将帮助我们理解细胞周期是如何调节细胞生长的。这两个目标将细胞生长联系在一起
从蛋白质合成的角度对细胞分裂进行调控。然后,蛋白质合成的研究
在细胞生长过程中被调节(Aim3)探索细胞大小如何反馈以调节生长的机制
费率。因此,这三个目标共同为更深入地理解这些原则奠定了基础
控制细胞的生长和增殖。
上述目标的完成将加深我们对基本分子机制的理解。
调节蛋白质合成和细胞生长速度,因此对细胞和发育有广泛的影响
生物学。此外,这项工作将加深我们对组织再生缺陷和
肿瘤发生学。在一个由导师、合作者和顾问组成的优秀团队的帮助下,我将在
数量生物学和分子生物学的前沿技术,并为我的职业生涯获得技能
发展。综上所述,拟议的科学和培训计划为独立的
在理解生理和病理条件下细胞生长原理方面的研究生涯。
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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{{ truncateString('Shuyuan Zhang', 18)}}的其他基金
Determine how protein synthesis is regulated during cell growth and division
确定细胞生长和分裂过程中蛋白质合成的调节方式
- 批准号:
10506035 - 财政年份:2022
- 资助金额:
$ 12.5万 - 项目类别:
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