Yusuke Himeoka - University of Tokyo, Japan
Biography
Title: A theoretical basis for cell deaths
Abstract: Comprehending cell death is one of the central topics of biological science. Currently, the criteria for microbial cell death are purely experimental, based on PI staining and regrowth experiments. In the present project, we aimed to develop a mathematical framework of cell death based on the metabolic state of the cells.
Our attempt is to develop a theoretical framework of “death” for cellular metabolism [1]. We start by defining dead states as cellular metabolic states that are not returnable to the predefined “representative living states”; regardless of the modulation of enzyme concentrations and external nutrient concentrations. The definition requires a method to compute the restricted, global, and nonlinear controllability, for which no general theory exists. We have developed “The Stoichiometric Rays”, a simple method to solve the controllability computation. This allows us to compute how the enzyme concentration should be modulated to control the metabolic state from a given state to a desired state.
Using the stoichiometric rays, we have computed the returnability of the non-growing state emerging in an in silico metabolic model of E. coli [2] to the growing state of the model, and found that the non-growing state is indeed a “dead” state. Furthermore, we have quantified “the Separating Alive and Non-life Zone (SANZ) hypersurface” [3] which divides the phase space into the living- and non-living regions.
In this talk, I would like to present our framework for cell death, including stoichiometric rays, and what we can learn from quantifying the SANZ hypersurface.
[1] Himeoka et al., (2024), arXiv, March. https://arxiv.org/abs/2403.02169.
[2] Boecker et al., (2021), Mol. Syst. Biol., 17 (12): e10504.
[3] The Sanzu hypersurface is derived from a mythical river in the Japanese Buddhist tradition, the Sanzu River that represents the boundary between the world of the living and the afterlife.
