Bistability and Biological Oscillations

描述（由申请人提供）：已经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的负反馈循环。第二个是负反馈回路与叠加的正反馈回路。通过计算研究和实验工作的结合，现在很清楚，爪蟾卵提取物中的Cdk/APC振荡器属于第二类，依赖于一个负反馈回路来产生持续的振荡。在这里，我们建议探讨这种正加负反馈设计的一般性和潜在的优势。该项目的具体目标是：1。为了检验正反馈允许细胞周期振荡的频率被调节而基本上不改变振幅振荡的假设。2.为了验证正反馈允许生化信号在大细胞（如青蛙卵）中传播的速度比扩散速度更快的假设。3.确定正反馈在体细胞系产生持续振荡中的作用。这些研究建立在对生物振荡器的系统生物学的理解的新概念进展以及生产这些研究的重要技术进展的基础上，这些研究应该有助于我们理解细胞周期振荡器和一般生物振荡器的设计原理。

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.