Synchronization of a budding yeast cell culture by manipulating inner cell cycle concentrations

摘要

The synchronization of cell populations is an important topic not only in research but also for biotechnological production processes. Synchronization means that all cells in the culture are in the same phase of the cell cycle and that they divide, at best, in unison. A synchronized cell culture is an important topic in molecular biology to analyze cell cycle events and to understand how the cells control growth and division. It has a high potential in biotechnological production processes because many products which are of commercial interest are cell cycle dependent or are synthesized in a cell cycle dependent manner. In this work a strategy for the synchronization of an in silico budding yeast cell culture is computed and analyzed. The in silico culture is based on a single cell cycle model taken from the literature which describes the cell cycle of Saccharomyces cerevisiae by the concentrations and interactions of proteins that participate in the cell cycle. By individually setting the parameters for each cell, the model can be used to model a non-homogenous cell population. The synchronization approach followed here is based on the manipulation of the concentrations of native proteins. The variation of two parameters in the model that can be achieved by different gene expression rates leads to a modified expression of two cyclins that appear in the late G1 phase. Dependent on the concentration of these two cyclins, the G1 phase can be either lengthened or shortened, thus maintaining the cells in the G1 phase or accelerating their transition to the other phases. Due to the non-convexity of the problem, the optimization is done by a memetic algorithm. The synchronization is applied to an exponential growing cell population inside a batch reactor and a chemostat. A detailed analysis of the effect of the expression levels is presented. For the chemostat, a periodic pattern for synchronizing and keeping the culture in synchrony is c- mputed.