Dynamic Regulation and Information Transfer in Intracellular-signaling Pathways Public Deposited

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Last Modified
  • March 21, 2019
Creator
  • Behar, Marcelo S.
    • Affiliation: College of Arts and Sciences, Department of Physics and Astronomy
Abstract
  • Cells contain myriads of specialized sensors that allow them to react to changes in the environment by activating pathways comprised by layers of signaling proteins. Cell survival requires these pathways to reliably propagate signals containing qualitative and quantitative information about their environment. They achieve this by modulating the enzymatic activity of signaling proteins. In this work we analyze some of these regulatory mechanisms, with emphasis on those that can be used to encode and decode quantitative information. In particular, we demonstrate that cells have the tools to encode quantitative information as signal-duration, and that by regulating pathways dynamics in a concerted way, they can ensure signal specificity in the presence of shared components without the need for cross-inhibition or scaffold proteins. A strategy termed kinetic insulation is introduced, which routes signals according to their temporal profile. We show that such a system can be built with regulatory motifs commonly observed in signaling pathways. We also present experimental evidence indicating that duration encoding is being used in the yeast pheromone response pathway. Computational modeling is used to analyze possible encoding mechanisms and key experiments are proposed that can distinguish among them. Finally, the importance of studying signals as dynamic events is discussed.
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  • In Copyright
Advisor
  • Dohlman, Henrik
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  • Open access
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