Inference of the High-Level Interaction Topology between the Metabolic and Cell-Cycle Oscillators from Single-Cell Dynamics

Ozsezen, S., Papagiannakis, A., Chen, H., Niebel, B., Milias-Argeitis, A. & Heinemann, M., 23-Oct-2019, In : Cell systems. 9, 4, p. 354-365 10 p., j.cels.2019.09.003.

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  • Inference of the High-Level Interaction Topology

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  • Inference of the High-Level Interaction Topologybetween the Metabolic and Cell-Cycle Oscillatorsfrom Single-Cell Dynamics

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Recent evidence suggests that the eukaryotic metabolism is an autonomous oscillator. Together with oscillating elements of the cyclin/CDK machinery, this oscillator might form a coupled oscillator system, from which cell-cycle control emerges. The topology of interactions between the metabolic oscillator and the elements of the cyclin/CDK machinery, however, remains unknown. Using single-cell metabolic and cell-cycle dynamics in yeast, and solving an inverse problem with a system of Kuramoto oscillators, we inferred how the metabolic oscillator interacts with the cyclin/CDK machinery. The identified and experimentally validated interaction topology shows that the early and late cell cycle are independently driven by metabolism. While in this topology, the S phase is coordinated by START. We obtained no support for a strong interaction between early and late cell cycle. The identified high-level interaction topology will guide future efforts to discover the molecular links between metabolism and the cell cycle.

Original languageEnglish
Article numberj.cels.2019.09.003
Pages (from-to)354-365
Number of pages10
JournalCell systems
Issue number4
Early online date9-Oct-2019
Publication statusPublished - 23-Oct-2019

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