CONTROLLING THE CELL CYCLE RESTRICTION SWITCH ACROSS THE INFORMATION GRADIENT

Jordan C. Rozum and Réka Albert
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Jordan C. Rozum: Department of Physics, The Pennsylvania State University, 121 Davey Laboratory, University Park, PA 16803, USA
Réka Albert: Departments of Physics and Biology, The Pennsylvania State University, 152E Davey Laboratory, University Park, PA 16803, USA

Advances in Complex Systems (ACS), 2020, vol. 22, issue 07n08, 1-21

Abstract: Boolean models represent a drastic simplification of complex biomolecular systems, and yet accurately predict system properties, e.g., effective control strategies. Why is this? Parameter robustness has been highlighted as a general feature of biomolecular systems and may play an important role in the accuracy of Boolean models. We argue here that a useful way to view a system’s controllability properties is through its repertoire of self-sustaining positive circuits (stable motifs). We examine attractor control and self-sustaining circuits within the cell cycle restriction switch, a bistable regulatory circuit that allows or prevents entry into the cell cycle. We explore this system using three models: a previously published Boolean model, a Hill kinetics model that we construct from the Boolean model using the HillCube methodology, and a reaction-based model we construct from the literature. We highlight the robustness of stable motifs across these three levels of modeling detail. We also show how consideration of control-robust regulatory circuits can aid in parameter specification.

Keywords: Cell cycle; systems biology; network control (search for similar items in EconPapers)
Date: 2020
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DOI: 10.1142/S0219525919500206

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