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Signaling networks are essential for coordinated cellular function in higher organisms, and breakdown of these cellular control systems is at the root of many diseases. Our lab uses live-cell microscopy to develop more accurate mechanistic models of key signaling pathways regulating cell proliferation and survival. Pathways including ERK, Akt, mTOR, AMPK, and Hippo are activated by factors in the cellular microenvironment (including growth factors, nutrients, extracellular matrix contacts, and cell-cell interactions). Through the phosphorylation of numerous targets, this core signaling network controls central aspects of cellular behavior such as metabolic flux, growth, and DNA replication, which in turn determine cell phenotypes such as proliferation, apoptosis, and autophagy. A long-standing challenge in cell biology has been to understand how this limited set of kinase/transcription pathways can achieve specific control of cell fate in response to the diverse set of inputs integrated by the network. A potential answer to this question is suggested by the highly dynamic and individualized single-cell dynamics of ERK and other components of the core network, including mTOR, Akt, and AMPK. Such dynamic patterns are capable of carrying a large quantity of information and are capable of determining cell fate. We are exploring the hypothesis that 1) the unique pattern of signaling dynamics within each cell encodes the integrated status of multiple aspects of the microenvironment and that 2) differential cell fates are be specified by decoding patterns of core pathway activity.