Evolution of cell cycle control: triangulating the last eukaryotic common ancestor

细胞周期控制的进化：最后一个真核共同祖先的三角测量

基本信息

批准号：
9893303
负责人：
FREDERICK R. CROSS
金额：
$ 5万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9893303
关键词：
Architecture Behavior Biological Biological Models Biology Cell Cycle Cell Cycle Regulation Cell Size Cell division Cells Chromatin Complex Conflict (Psychology)Coupling Cyclins Data Dimensions Equilibrium Eukaryotic Cell Event Evolution Explosion Feedback Fluorescence Microscopy Funding Gene Cluster Gene Expression Genes Genetic Genetic Transcription Growth and Development function Human Development Individual Link M cell Measures Methods Mitosis Mitotic Modeling Molecular Newborn Infant Noise Nucleosomes Organism Peripheral Phase Phosphoric Monoester Hydrolases Phosphotransferases Process Proteins Regulation Regulon S Phase Saccharomycetales Source System Systems Theory Testing Time Work Yeast Model System automated image analysis base biological systems cost dynamic system event cycle experimental study human disease innovation insight mathematical methods mathematical model polarized cell promoter recruit response success transcription factor

项目摘要

Project Summary Cell cycle control is highly conserved through the eukaryotic kingdom, and the budding yeast model system has been the source of major insights applicable to issues in human development and disease. This proposal continues systems-level analysis of the eukaryotic cell cycle using this model system. The cell cycle `clock' functions with high reliability and low noise, even though individual components and circuits making up the clock are frequently known to be highly variable. For example, gene expression is known to be highly variable between individual cells, and yet cell-cycle-regulated gene expression can be highly reliable with respect to timing and amplitude. Threshold responses to rising cyclin-Cdk activity levels can provide switch-like behavior, but such switches can frequently come at the cost of highly variable onset time; the overall cell cycle control circuitry avoids this variability. We are pursuing an emerging concept of multiple independent oscillators contributing to cell cycle control; while uncoupled oscillators result in highly variable and irregular sequences of cell cycle events, we propose that coupling (`phase-locking') of otherwise independent oscillators to the central cyclin-Cdk oscillator can yield a robust and accurate overall system. This proposal continues our innovative use of quantitative time-lapse fluorescence microscopy, over multi-cell cycle timescales, combined with semi-automated image analysis and in-depth genetic and quantitative analysis to drive systems-level understanding of cell cycle control. We are developing new methods of mathematical modeling. There is a pressing need in biology for simple but experimentally constrained models that can reveal basic control principles. The challenge is to find the most illuminating balance between the detail required for a connection to biological reality, and model simplicity required for transparency and insight. We are exploring methods to use geometrical, low-dimensionality representations of the cell cycle control network that can still be experimentally constrained, and that will yield testable predictions.

项目摘要细胞周期控制通过真核王国高度保守，萌芽的酵母模型系统一直是适用于人类发展和疾病问题的主要见解的来源。这个建议使用此模型系统继续对真核细胞周期进行系统级分析。即使单个组件和构成时钟的电路通常是可变的。例如，基因表达是已知在单个细胞之间是高度变化的，但是细胞周期调节的基因表达可以是在时间和振幅方面高度可靠。阈值对Cyclin-CDK活性水平上升的阈值响应可以提供类似开关的行为，但是这种开关通常可以以高度可变的发作时间来实现；总体细胞周期控制电路避免了这种可变性。我们正在追求一个新兴的多重概念有助于细胞周期控制的独立振荡器；而未耦合的振荡器导致高度可变和细胞周期事件的不规则序列，我们提出了否则的耦合（“相锁”）中央细胞周期蛋白CDK振荡器的独立振荡器可以产生强大而准确的总体系统。该建议继续我们对定量延时荧光显微镜的创新使用，而不是多细胞周期时间尺度，与半自动图像分析以及深入的遗传和定量结合分析以驱动系统级别对细胞周期控制的理解。我们正在开发新的数学建模方法。生物学对简单但可以揭示基本控制原理的实验约束模型。挑战是找到最多的在与生物现实联系所需的细节与模型简单性之间的详细信息之间保持平衡透明度和见识所需。我们正在探索使用几何，低维度的方法细胞周期控制网络的表示，仍然可以通过实验限制，这将产生可检验的预测。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

F-actin homeostasis through transcriptional regulation and proteasome-mediated proteolysis.

F-肌动蛋白通过转录调节和蛋白酶体介导的蛋白水解实现稳态。

DOI：
10.1073/pnas.1721935115
发表时间：
2018
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Onishi,Masayuki;Pecani,Kresti;Jones4th,Taylor;Pringle,JohnR;Cross,FrederickR
通讯作者：
Cross,FrederickR

Regulated degradation of the APC coactivator Cdc20.

APC 共激活剂 Cdc20 的降解受到调节。

DOI：
10.1186/1747-1028-5-23
发表时间：
2010
期刊：
Cell division
影响因子：
2.3
作者：
Robbins,JonathanA;Cross,FrederickR
通讯作者：
Cross,FrederickR

Cleavage-furrow formation without F-actin in Chlamydomonas

DOI：
10.1073/pnas.1920337117
发表时间：
2020-08-04
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Onishi，Masayuki;Umen，James G.;Pringle，John R.
通讯作者：
Pringle，John R.

High-Throughput Robotically Assisted Isolation of Temperature-sensitive Lethal Mutants in Chlamydomonas reinhardtii.