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CS441: Systems Biology II

The Importance of Activator-Repressor Balance for Various Models of Sequestration in Circadian Clocks

Abstract: To understand protein networks, scientists use mathematical models to simulate the various molecules and their interactions. These mathematical models are differential equations for the concentrations of molecules over time. When constructing a model, it is important to choose a level of abstraction that makes models as simple as possible, without losing their key robustness properties. For oscillating systems, the ability to maintain oscillations is key. In a recent publication Kim and Forger (2012) discuss the relationship between the ratio of repressor and activator proteins and the robustness of a system’s oscillations and conclude that a 1:1 ratio is best. Here, we examine three additional models of circadian processes (Leloup and Goldbeter, 2003; Mirsky et al, 2009; and Ueda et al 2000) and seek to determine which model structures lead to the situation in which a 1:1 repressor to activator ratio gives rise to a more robust system. For each of the models, we modify the mode of repression using three different levels of abstraction: explicit sequestration, implicit sequestration, and direct Hill repression.

Mary Fletcher, Roxana Gheorghe, Olivia Lang, Stephanie Taylor, 2013



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