Quantitative validation of regulatory modules predicted by mathematics based on network topology

What is it about?

For cells to survive, chemical reactions with various functions must occur within the cell, and each must be appropriately regulated. It is known that all reactions within a cell form a single interconnected network, as the products of one reaction serve as substrates for another. But is it actually possible to individually regulate different substances that perform different functions within a single, interconnected dynamic system? Yuhei Yamauchi and Atsushi Mochizuki at the Institute for Life and Medical Sciences, Kyoto University, along with their colleagues, have previously demonstrated through mathematical theory that when a part of a reaction network satisfies a certain mathematical equation, it forms a “buffering structure” and acquires “modularity”—the ability to be controlled independently of other parts of the network. In this latest study, through a collaborative effort with Hiroki Sugiyama of the Institute for Earth and Life Sciences at Institute of Science Tokyo, Yuhei Goto, and Kazuhiro Aoki of the Graduate School of Biostudies at Kyoto University, the researchers demonstrated that this buffering structure actually exists within the “cell cycle system”—which governs the life stages of cells—and plays a crucial role. Analysis of the cell cycle system suggested that two types of protein complexes, which regulate cell cycle transitions, are contained within different buffering structures and may therefore be controlled independently of one another. Using the latest quantitative analysis, the research group confirmed that one protein complex indeed behaves independently of the other. Furthermore, by comparing theoretical predictions with experimental verification, they theoretically predicted an unknown reaction and proved its existence through verification experiments.

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Photo by BoliviaInteligente on Unsplash

Photo by BoliviaInteligente on Unsplash

Why is it important?

This research demonstrated that buffering structures—a principle of independent control or modularity predicted mathematically—do indeed exist in actual biological systems and perform critical functions for cells. Furthermore, by using theoretical predictions and experimental verification, the research group identified a previously unknown reaction in the yeast cell cycle system, thereby updating our understanding of a system that has long been studied in molecular biology. That is a proposal of a new approach to systems biology—one that derives unknown information as requirements by combining model-free theory with experimental validation.

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