QSB: Understanding Bistability in Complex Enzyme-Driven Reaction Networks

本研究的主要重点是推导生化网络中多个稳定状态或持续振荡的充分必要条件。首席研究员（PI）用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也表现出双稳定性。该结果是由PI先前开发的化学反应网络理论推导出来的。该理论的一个主要成果是缺陷零定理，该定理排除了大量网络中的双稳态或持续振荡。这些结果在PI编写的化学反应网络工具箱中进行了扩展和实现。PI还开发了分析大型网络的图形方法。虽然这些方法已被证明足以分析化学工程问题，但当面对自然发生的生化网络的复杂性时，它们就失败了，因为这些网络包含用于同一反应的多种酶。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，它并没有提供断言多重稳态存在的条件。PI建议开发这样的条件。PI计划将区分多个稳定状态竞争机制的改进方法纳入新理论。他还将开发一种绘制和分析物种反应图的计算机算法。

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.