An integrated model of metabolism, growth and cell cycle in budding yeast

Mathematical models of biochemical systems are expected to have a strong impact on systems biology and systems medicine, as they increase the understanding of how complex biological functions arise from the interactions of large numbers of gene products and biologically active molecules. Recent papers underline the need to develop quantitative models of the whole cell in order to tackle this challenge and to accelerate biological discoveries [1]. In this work we present iMeGroCy, an integrated multi-scale coarse-grain model of Metabolism, cell Growth and cell Cycle, that allows to simulate the growth of a yeast cell under different nutritional conditions. The three major functions considered by iMeGroCy are described by means of two coarse-grain models: MeGro, the sub-module of Metabolism and Growth, and GroCy, the sub-module of Growth and Cycle. The two sub-modules are linked together in a unified, low granularity framework, where MeGro acts as a parameter generator for GroCy. iMeGroCy can be extended to the population level, predicting with high accuracy protein distributions of growing yeast populations, that are information-rich descriptors of the physiological state of the cell. The modular nature of iMeGroCy allows to insert molecularly detailed sub-models of yeast functions, providing a proper scaffold for probing the plugged-in functions in the context of a cycling cell. [1] Karr, J. R., Sanghvi, J. C., Macklin, D. N., Gutschow, M. V., Jacobs, J. M., Bolival, B., Assad-Garcia, N., Glass, J. I., Covert, M.W. (2012) A Whole-Cell Computational Model Predicts Phenotype from Genotype. Cell 150, 389-401.