QSB: Understanding Bistability in Complex Enzyme-Driven Reaction Networks

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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.