日時：	2024年1月26日（金）15：00～16：30
場所：	医生物学研究所　医生研3号館5階501室 Room 501, 5th floor, Bldg. #3 Institute for Life and Medical Sciences, Kyoto University
演者：	Dr. Yusuke Himeoka The University of Tokyo
演題：	Perturbation-response analysis and death of in silico Escherichia coli metabolism

講演要旨

Abstract: Systems biology, focusing on microorganisms such as Escherichia coli, has unearthed several mathematical laws over the past decades, such as the growth rate-ribosome relationship, flux balance analysis, and cell size control in exponential growth phases. The steady-state assumption plays a central role in these mathematical laws. But in the complex system of a “cell”, where over a thousand types of chemical substances and reactions interact, should the existence and stability of a steady state be taken so uncritically for granted? Might it instead be crucial to ask under what conditions a stable steady state can exist in order to understand the state of being “alive”?

Recently, slow dynamics and memory phenomena have been found to occur in cellular physiological states under stressful environments, suggesting that theories based solely on steady states are inadequate for understanding them. Both theoretical interest and experimental demand point to the need to develop a theoretical framework for kinetics that goes beyond metabolic statics.

To this end, as a first step in understanding the dynamic aspects of cells, we have investigated how metabolic dynamics respond to perturbations in metabolite concentrations using several models. It was found that the kinetic models of E. coli metabolism show strong responses to perturbations compared to toy models of metabolism. Moreover, in some models, perturbations in metabolite concentrations induced very slow relaxation dynamics, similar to the behavior of E. coli in the dormant state. Further analysis revealed that cofactors such as ATP or ADP and the structure of the metabolic network play a crucial role in the strong responsiveness.

In addition, when the perturbations were intensified, some models exhibited states corresponding to “cell death” with zero growth rate. We elucidated the mechanism behind this model cell death and identified the point of no return in the model, where no further resurrection is possible, regardless of how gene expression states are controlled.

In this seminar, I will present the above findings and discuss how they can be used to understand the fundamental differences between “living” and “dead” states and the difficulties of creating cells from scratch.

 

contact: Takashi Okada

Laboratory of Mathematical Biology,

Institute for Life and Medical Sciences, Kyoto University

Email: okada.Takashi.3z＊infront.kyoto-u.ac.jp (＊を@へ変えてください。)