Cell ensemble modeling of metabolic oscillations in continuous yeast cultures

Abstract

Continuous cultures of the yeast Saccharomyces cerevisiae exhibit autonomous oscillations under certain environmental conditions. Three distinct type of oscillations have been experimentally observed and characterized: glycolytic oscillations, respiratory oscillations and cell cycle related oscillations. Because they are metabolically driven and independent of cell cycle progression, glycolytic and respiratory oscillations are well suited for the study of intracellular metabolism and regulatory dynamics. The incorporation of metabolic structure within the cell population balance equation (PBE) framework leads to computational infeasibility due to the high dimensionality of the cell distribution function. An alternative approach based on large ensembles of metabolically structured cell models is shown to be effective for modeling the synchronization of glycolytic and respiratory oscillations. A simple method for computing transient number distribution functions from ensemble simulation data is presented. The paper concludes with a brief overview of our future work on ensemble modeling of respiratory and cell cycle related oscillations.