Speaker
Description
In living cells, numerous chemical reactions are interconnected by sharing substrates and products, forming a reaction network. Various functions of cells emerge from dynamics of such interconnected system. Cells regulate amount of key chemicals by controlling amount/activity of enzymes, thereby achieving control of cellular functions. However, in such an interconnected system, can different chemicals responsible for different biological functions be controlled independently? We mathematically demonstrate that “modularity”, where parts of a system are controlled independently of others, arises solely from network topology. We found that the qualitative response of chemical concentrations to changes in enzyme amount/activity are localized to finite ranges in a network, and each range is determined by a subnetwork called a “buffering structure”, that is defined by the equation $\chi≔-$(# of chemicals)$+$(# of reactions)$-$(# of cycles)$+$(# of conserved quantities)$=0$ from local topology of a network. Using the cell cycle system as an example, we show that buffering structures actually exist in living organisms, performing important roles. In the cell cycle, the G1-S and G2-M transitions are strictly controlled by distinct protein complexes, requiring the activation of different complexes at different phases. Analysis of the cell cycle network revealed that the two complexes belong to different buffering structures. Moreover, by comparing theoretical predictions with experimental verification, we theoretically predict the necessity of an unknown reaction and experimentally confirm it.
Bibliography
@article{Mochizuki_Fiedler_2015,
title={Sensitivity of chemical reaction networks: a structural approach},
volume={367},
url={https://www.sciencedirect.com/science/article/abs/pii/S0022519314006158},
DOI={10.1016/j.jtbi.2014.10.025},
journal={J. Theor. Biol.},
author={Mochizuki, Atsushi and Fiedler, Bernold},
year={2015}, pages={189-202}, language={en}
}
@article{Okada_Mochizuki_2016,
title={Law of Localization in Chemical Reaction Networks},
volume={117},
url={https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.117.048101},
DOI={10.1103/PhysRevLett.117.048101},
journal={Physical Review Letters},
author={Okada, Takashi and Mochizuki, Atsushi},
year={2016}, pages={048101}, language={en}
}
@article{Okada_Mochizuki_2017,
title={Sensitivity and Network Topology in Chemical Reaction Systems},
volume={96},
url={https://journals.aps.org/pre/abstract/10.1103/PhysRevE.96.022322},
DOI={10.1103/PhysRevE.96.022322},
journal={Physical Review E},
author={Okada, Takashi and Mochizuki, Atsushi},
year={2017}, pages={032416}, language={en}
}
@article{Yamauchi_etal_2024,
title={Finding regulatory modules of chemical reaction systems},
volume={6},
url={https://journals.aps.org/prresearch/abstract/10.1103/PhysRevResearch.6.023150},
DOI={10.1103/PhysRevResearch.6.023150},
journal={Physical Review Research},
author={Yamauchi, Yuhei and Hishida, Atsuki and Okada, Takashi and Mochizuki, Atsushi},
year={2024}, pages={023150}, language={en}
}
@article{Yamauchi_etal_2026,
title={Network topology creates independent control of G2-M from G1-S checkpoints in the fission yeast cell cycle system},
url={https://doi.org/10.1101/2025.10.21.683796},
DOI={10.1101/2025.10.21.683796},
journal={bioRxiv},
author={Yamauchi, Yuhei and Sugiyama, Hironori and Goto, Yuhei and Kazuhiro, Aoki and Mochizuki, Atsushi},
year={2025}, month=march, language={en}
}
