Bistability and Biological Oscillations

双稳定性和生物振荡

• 批准号: 7080671
• 负责人: JAMES E. FERRELL
• 金额: $ 26.64万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7080671
• 关键词: HeLa cells; Xenopus; Xenopus oocyte; biological signal transduction; bioperiodicity; cell cycle; circadian rhythms; computational biology; cyclins; fluorescent dye /probe; synchronous cell division; tissue /cell culture

DESCRIPTION (provided by applicant): Two basic designs have been described for biological oscillators. The first and simplest is a long negative feedback loop. The second is a negative feedback loop with a positive feedback loop superimposed. Through a combination of computational studies and experimental work, it is now clear that the Cdk/APC oscillator in Xenopus egg extracts belongs to this second class, relying on a bistable positive feedback loop to produce sustained oscillations. Here we propose to explore the generality and potential advantages of this positive-plus-negative feedback design. The Specific Aims of this project are: 1. To test the hypothesis that positive feedback allows the frequency of cell cycle oscillations to be adjusted without substantially altering the amplitude oscillations. 2. To test the hypothesis that positive feedback allows biochemical signals to propagate across a large cell (like a frog egg) faster than the speed of diffusion. 3. To determine the role of positive feedback in generating sustained oscillations in a somatic cell line. These studies build upon new conceptual advances in the understanding of the systems biology of biological oscillators, and important technical advances in the production of These studies should help us to understand the design principles of the cell cycle oscillator, and of biological oscillators in general.

描述（由申请人提供）：已经描述了针对生物振荡器的两个基本设计。第一个也是最简单的是一个长的负面反馈循环。第二个是一个负反馈循环，并叠加了正反馈循环。通过计算研究和实验性工作的结合，很明显，Xenopus鸡蛋提取物中的CDK/APC振荡器属于该第二类，这依靠可动的正反馈回路来产生持续的振荡。在这里，我们建议探索这种正面反馈设计的一般性和潜在优势。该项目的具体目的是：1。检验假设，即阳性反馈允许调整细胞周期振荡的频率而不实质上改变振幅振荡。 2。检验假设，即阳性反馈允许生化信号比扩散速度更快地传播大细胞（例如青蛙卵）。 3。确定阳性反馈在体细胞系中产生持续振荡中的作用。这些研究以对生物学振荡剂系统生物学的理解为基础，这些研究的生产以及这些研究的重要技术进步应有助于我们了解细胞周期振荡器的设计原理以及一般的生物振荡器的设计原理。