Coarse-grained modelling to guide an understanding of eukaryotic cell physiology (360G-Wellcome-203968_Z_16_A)

Unicellular organisms resemble factories that produce copies of themselves. In order to optimise growth, they adjust their relative allocation of resources to the various subprocesses that construct all necessary components of a new cell. In bacteria, these optimisations have been observed in many conditions. Generally, the fraction of ribosomal proteins scales linearly with the cellular growth rate. This suggests that bacteria are highly optimised for fast growth under many conditions. In a preliminary analysis, we have observed the same linear relation between growth rate and ribosomal protein allocation in yeast cells, grown using various sources of nitrogen. The shift towards expressing more growth-related ribosomal proteins occurs together with the cells needing fewer resources to utilise their nitrogen source. In the project, we will extend this analysis and use the results to inform a coarse-grained cell model. Our model should allow us to understand the principles of growth and biomass production. Because the eukaryote from this study is more closely related to human cells than bacteria, our results provide a stepping stone in developing anti-cancer treatments. In both synthetic biology and anti-cancer research, understanding the balance between growth and protein production is crucial towards obtaining good yields and/or controlling runaway growth.