Yeast population models for monitoring and control of biotechnical processes

Abstract

Recent technological developments allow the measurement of segregated parameters of cell populations (cell size; protein, DNA and RNA contents) on significant samples of the population (10⁵–10⁶ cells). To exploit this information and to develop control approaches based on these parameters, which are more directly related to the growth metabolism, it is necessary to use structured mathematical models of cell populations. In the paper a more general version of a growth-controlled structured model previously developed is presented, which is able to describe cell growth, unequal division and genealogical heterogeneity of budding yeast (Saccharomyces cerevisiae), and, from the model, age and size distributions for populations in steady states of growth are derived. In several conditions, both in batch and in continuous cultures, the experimental protein distributions, obtained by flow cytometry, are shown to accurately fit those predicted by the model and to contain relevant information on the conditions of growth of the microbial biomass. Furthermore, these distributions have a predictive value on process dynamics, being very sensitive to changes in synthesis and division rates, as experiments in batch reactors and in chemostats have shown, and may, therefore, find a use in the development of new control approaches for microbial reactors.