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Decision points to enter and exit the human cell cycle

进入和退出人体细胞周期的决策点

基本信息

批准号：
9270039
负责人：
TOBIAS MEYER
金额：
$ 28.33万
依托单位：
STANFORD UNIVERSITY
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：
2016-05-09 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9270039
关键词：
Alpha Cell Antibodies Back Binding Biochemical Biosensor CCNE1 gene Cell Cycle Cell Cycle Regulation Cell model Cells Communities Cyclin A DNA biosynthesis Data Data Analyses Decision Making Degenerative Disorder Disease E2F transcription factors E2F1 gene Event Experimental Models G1 Phase Goals Growth Growth Factor Hour Human Immune response Individual Laboratories Link Malignant Neoplasms Mammalian Cell Maps Measurement Measures Mediating Messenger RNA Methodology Methods Mitosis Modeling Molecular Monitor Nerve Degeneration Neurodegenerative Disorders Outcome Phosphotransferases Population Post-Translational Protein Processing Process Proliferating Proteins Ramp Reporter S Phase Signal Transduction Site Stimulus Stress Testing Therapeutic Time Tissues Transcriptional Activation Treatment-Related Cancer Up-Regulation Work Wound Healing anticancer research base cell type improved predictive modeling public health relevance repaired response single cell analysis temporal measurement tissue degeneration tool ubiquitin-protein ligase

项目摘要

DESCRIPTION (provided by applicant): Diseases associated with cancer, immune responses, wound healing, and neurodegeneration are often caused by insufficient or excessive proliferation of particular human cell types. Under normal conditions, such cells have to robustly control if and when they proliferate to maintain and repair functioning tissues. While little is known about how cells exit the cell cycle, the decision to enter the cell cycle is often referred t as a "restriction point", a point where growth factors can be removed and cells still enter and complete the cell cycle. However, our recent single cell data analysis suggests that this fundamentally important decision is made by a different mechanism involving a cell cycle priming and a final cell cycle commitment step. Our proposed work will make use of automated single live cell and fixed cell analysis using biosensor and activity selective antibodies to measure key cell cycle regulatory events and to dissect the control circuits of cell cycle entry and exit. Our final goal is to develop and validate a quantitative model for cell cycle entry and exit. The outcome of the proposed work will be the identification, characterization and modeling of critical proliferation control points that can be exploited therapeutically to treat diseases suh as cancer, immune responses, wound healing, as well as neurodegenerative diseases. For many growth associated diseases, treatment will likely involve strategies to regulate the rate of proliferation of specific cell types. In addition, our work will provide the cell cycle and cancer research communities with experimental and modeling tools to investigate cell specific cell cycle control in different cell types.

描述（由申请人提供）：与癌症、免疫反应、伤口愈合和神经变性相关的疾病通常由特定人类细胞类型的增殖不足或过度引起。在正常情况下，这些细胞必须强有力地控制它们是否以及何时增殖以维持和修复功能组织。虽然对细胞如何退出细胞周期知之甚少，但进入细胞周期的决定通常被称为“限制点”，即生长因子可以被去除而细胞仍然进入并完成细胞周期的点。然而，我们最近的单细胞数据分析表明，这一根本性的重要决定是由一个不同的机制，涉及细胞周期启动和最终的细胞周期承诺步骤。我们提出的工作将利用自动化的单个活细胞和固定细胞分析，使用生物传感器和活性选择性抗体来测量关键的细胞周期调控事件，并剖析细胞周期进入和退出的控制电路。我们的最终目标是开发和验证细胞周期进入和退出的定量模型。拟议的工作的结果将是识别，表征和建模的关键增殖控制点，可以利用治疗疾病，如癌症，免疫反应，伤口愈合，以及神经退行性疾病。对于许多生长相关疾病，治疗可能涉及调节特定细胞类型增殖速率的策略。此外，我们的工作将为细胞周期和癌症研究社区提供实验和建模工具，以研究不同细胞类型中的细胞特异性细胞周期控制。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Irreversible APC(Cdh1) Inactivation Underlies the Point of No Return for Cell-Cycle Entry.

DOI：
10.1016/j.cell.2016.05.077
发表时间：
2016-06-30
期刊：
Cell
影响因子：
64.5
作者：
Cappell SD;Chung M;Jaimovich A;Spencer SL;Meyer T
通讯作者：
Meyer T

Measuring Signaling and RNA-Seq in the Same Cell Links Gene Expression to Dynamic Patterns of NF-κB Activation.

DOI：
10.1016/j.cels.2017.03.010
发表时间：
2017-04-26
期刊：
Cell systems
影响因子：
9.3
作者：
Lane K;Van Valen D;DeFelice MM;Macklin DN;Kudo T;Jaimovich A;Carr A;Meyer T;Pe'er D;Boutet SC;Covert MW
通讯作者：
Covert MW