Determine how protein synthesis is regulated during cell growth and division
Determine how protein synthesis is regulated during cell growth and division
批准号:
10506035
负责人:
Shuyuan Zhang
金额:
$10.0万
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
项目状态:
已结题
起止时间:
2022-09-07 至 2024-08-31
关键词:
Abnormal CellAddressAffectB-LymphocytesBackBiogenesisBiologyCell CountCell CycleCell Cycle ProgressionCell Cycle StageCell MaintenanceCell ProliferationCell SizeCell divisionCell physiologyCellsCellular biologyComplexCyclin-Dependent KinasesCyclinsDataDevelopmentDevelopmental BiologyDiseaseEquilibriumFeedbackFeedsFoundationsG1/S TransitionGrowthHomeostasisHumanHyperplasiaHypertrophyImpairmentInvestigationKnowledgeLawsLeadLinkLiverMalignant NeoplasmsMammalian CellMass Spectrum AnalysisMeasuresMediatingMentorsMessenger RNAMolecularMolecular BiologyNatural regenerationPathologicPhasePhysiologicalProcessPropertyProtein BiosynthesisProteinsProteomeRB1 geneRNA-Binding ProteinsRegulationResearchRetinoblastoma ProteinRibosomal ProteinsRibosomal RNARibosomesS phaseTechnologyTestingTissuesTrainingTraining ProgramsTransfer RNATranslational RegulationTranslationsWorkcareercareer developmentcell growthcell growth regulationhealingin vivo Modelinhibitorinsightlive cell imagingliver cell proliferationrate of changeskillstime usetissue regenerationtumorigenesis
中文摘要
项目总结/文摘
英文摘要
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.
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Determine how protein synthesis is regulated during cell growth and division
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批准号:10700156
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项目类别:
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资助金额:$12.5万
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财政年份:2022
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负责人:Shuyuan Zhang
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依托单位:
海外基金