The role of feedback in signaling dynamics

TL;DRAbstract

This dissertation analyzes the dynamics of the individual components in two specific biological networks in order to understand how these components interact to produce observed cellular behavior. First, we use an integrated experimental-computational approach to analyze the dynamical response of a synthetic positive feedback network in individual mammalian cells. Using flow cytometry, we observe a switch-like activation of the network with variable delay times in individual cells. In agreement with a stochastic model of the network, we find that increasing the strength of the positive feedback results in a decrease in the mean delay time and a more coherent activation of individual cells. The results of this work are important for gaining insight into biological processes such as cell cycle regulation and apoptosis which rely on positive feedback to generate switch-like responses and may also facilitate the development of engineered mammalian control systems. Second, we use computatio

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