Bistability and Biological Oscillations

描述（由申请人提供）：描述了两种生物振荡器的基本设计。第一个也是最简单的是一个很长的负反馈循环。第二种是负反馈回路与正反馈回路叠加。通过计算研究和实验工作的结合，现在很清楚，非洲爪蟾卵提取物中的Cdk/APC振荡器属于第二类，依靠双稳态正反馈回路产生持续振荡。在这里，我们建议探索这种正加负反馈设计的通用性和潜在优势。本项目的具体目标是：1。为了验证这一假设，即正反馈允许细胞周期振荡的频率被调整，而不会实质性地改变振幅振荡。2. 为了验证这个假设，即正反馈允许生化信号在一个大细胞（比如青蛙卵）中传播的速度比扩散的速度快。3. 确定正反馈在产生体细胞持续振荡中的作用。这些研究建立在对生物振荡器的系统生物学理解的新概念上的进步，以及生产这些研究的重要技术进步，这些研究应该有助于我们理解细胞周期振荡器的设计原则，以及一般的生物振荡器。

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.