Bistability and Biological Oscillations

描述了生物振荡器的两种基本设计。第一个也是最简单的是一个长负数 反馈环路。第二种是叠加了正反馈环的负反馈环。 通过计算研究和实验工作的结合，现在可以清楚地看到，CDK/APC 非洲爪哇卵提取液中的振荡器属于这第二类，依赖于一个双稳态正反馈回路 产生持续的振荡。在这里，我们建议探索通用的和潜在的优势 这种正加负反馈的设计。 该项目的具体目标是： 1.检验正反馈允许调整细胞周期振荡频率的假设 而不会实质上改变幅度振荡。 2.检验正反馈允许生化信号在大型细胞中传播的假设 (像青蛙蛋)比扩散速度快。 3.确定正反馈在体细胞系中产生持续振荡的作用。 这些研究建立在理解生物学系统生物学的新概念进展的基础上。 振荡器，以及在这些研究的生产中取得的重要技术进步应有助于我们 了解细胞周期振荡器和一般生物振荡器的设计原理。

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.