QSB: Understanding Bistability in Complex Enzyme-Driven Reaction Networks

Feinberg0425459本研究的主要目的是得到生化网络存在多个稳态或持续振荡的充要条件。首席调查员(PI)以一个简单的酶驱动反应的例子来激励研究，即使在没有明显反馈的情况下，该反应也表现出双稳。这一结果是利用PI以前发展的化学反应网络理论得出的。这一理论的一个主要结果是亏零点定理，它排除了一大类网络中的双稳态或持续振荡。这些结果被扩展并在化学反应网络工具箱中实现，该软件由PI编写。PI还开发了用于分析较大网络的图解方法。虽然这些方法已被证明足以分析化学工程问题，但当面对复杂的自然发生的生化网络时，它们失败了，这些网络包含同一反应的多个酶。因此，需要发展新的理论。化学反应网络理论主要给出了排除双稳态的判据，但当这些判据失效时，它不能提供断言存在多个稳态的条件。私隐专员公署建议发展这些条件。PI计划在新的理论中纳入区分多个稳态的竞争机制的改进方法。他还将开发一种计算机算法来绘制和分析物种-反应图。

Feinberg0425459 The main focus of this research is to derive necessary and sufficient conditions for multiple steady states or sustained oscillations in biochemical networks. The Principal Investigator (PI) motivates the research with a simple example of an enzymatically driven reaction that exhibits bistability even in the absence of apparent feedback. The result is derived using chemical reaction network theory previously developed by the PI. A major result from this theory is the Deficiency Zero Theorem that rules out bistability or sustained oscillations in a large class of networks. These results were extended and implemented in the Chemical Reaction Network Toolbox, software written by the PI. The PI has also developed graphical methods for analyzing larger networks. While these methods have proven adequate for analyzing chemical engineering problems, they fail when faced with the complexity of naturally occurring biochemical networks that contain multiple enzymes for the same reaction. Therefore, new theories need to be developed. Chemical reaction network theory mainly gives criteria for ruling out bistability, but when these criteria fail it does not provide conditions for asserting the existence of multiple steady states. The PI proposes to develop such conditions. The PI plans to incorporate into the new theory refined methods for discriminating competing mechanisms for multiple steady states. He also will develop a computer algorithm for drawing and analyzing the Species-Reaction Graph.