16:10 〜 16:30
[MIS08-08] Understanding the boundary of life and death
★Invited Papers
Understanding the boundary between cell death and life is a fundamental issue in biology. In the talk, I would like to discuss how we can understand 'cell death' as a mathematical science, focusing on the death of microbial cells.
Research on microbial cell death has progressed by determining cell death markers that are empirically known and identifying the molecular mechanisms that drive related biochemical processes. However, there has been little discussion of what death is in the first place, or how it can be 'defined'. In addition, it has recently been reported that frequently used cell death assays such as dead cell staining and metabolic activity measurement can produce different results, and there is a growing need to discuss 'what constitutes "death"'.
In this study, we proposed the following definition: 'If a cell cannot return to a predetermined "representative living state" no matter how the gene expression level or external nutrient concentration is controlled, then we call it "dead"'. For instance, plant seeds appear to be 'dead' because they do not show any biochemical activity, but we do not regard plant seeds as dead material because they sprout when water is added. The proposal in this study is based on the lesson from plant seed, that is, to determine whether a cell is alive or dead based on whether or not such an operation as 'adding water' exists [1].
It is impossible to prove experimentally that 'no matter how you manipulate it, the cell cannot regain its activity', but it is possible with a mathematical model, in principle. We developed a method called 'Stoichiometric Rays' for computing the controllability of metabolic reaction systems in mathematical models. We succeeded in computing the 'state in which it is impossible to control the "representative living state" no matter how the amount of enzymes and external nutrient concentration are controlled' and quantifying the Separating Alive and Non-life Zone (SANZ) Hypersurface, which divides the 'living state' and 'dead state' in metabolic mathematical models [2]. In this talk, I will outline the framework, explain the quantification of the SANZ hypersurface and its biological interpretation, and discuss what we can think about 'what is life?'.
[1] Himeoka et al., 2024, Phys. Rev. Res. 6 (4): 043217.
[2] Boecker et al., 2021, Mol. Syst. Biol. 17 (12): e10504.
Research on microbial cell death has progressed by determining cell death markers that are empirically known and identifying the molecular mechanisms that drive related biochemical processes. However, there has been little discussion of what death is in the first place, or how it can be 'defined'. In addition, it has recently been reported that frequently used cell death assays such as dead cell staining and metabolic activity measurement can produce different results, and there is a growing need to discuss 'what constitutes "death"'.
In this study, we proposed the following definition: 'If a cell cannot return to a predetermined "representative living state" no matter how the gene expression level or external nutrient concentration is controlled, then we call it "dead"'. For instance, plant seeds appear to be 'dead' because they do not show any biochemical activity, but we do not regard plant seeds as dead material because they sprout when water is added. The proposal in this study is based on the lesson from plant seed, that is, to determine whether a cell is alive or dead based on whether or not such an operation as 'adding water' exists [1].
It is impossible to prove experimentally that 'no matter how you manipulate it, the cell cannot regain its activity', but it is possible with a mathematical model, in principle. We developed a method called 'Stoichiometric Rays' for computing the controllability of metabolic reaction systems in mathematical models. We succeeded in computing the 'state in which it is impossible to control the "representative living state" no matter how the amount of enzymes and external nutrient concentration are controlled' and quantifying the Separating Alive and Non-life Zone (SANZ) Hypersurface, which divides the 'living state' and 'dead state' in metabolic mathematical models [2]. In this talk, I will outline the framework, explain the quantification of the SANZ hypersurface and its biological interpretation, and discuss what we can think about 'what is life?'.
[1] Himeoka et al., 2024, Phys. Rev. Res. 6 (4): 043217.
[2] Boecker et al., 2021, Mol. Syst. Biol. 17 (12): e10504.