GHEORGHE MARIA, ANDREEA GEORGIANA SCOBAN SETTING SOME MILESTONES WHEN MODELLING CELL GENE EXPRESSION REGULATORY CIRCUITS UNDER VARIABLE-VOLUME WHOLE-CELL MODELLING FRAMEWORK. II While in the first part of the study, general concepts of the novel whole-cell simulation of metabolic processes in living cells are presented, by considering a variable-volume modelling framework, in the present paper exemplification is made for approaching several case studies when building-up modular model structures, for instance by developing modular kinetic representations of the homeostatic gene expression regulatory modules (GERM) that control the protein synthesis and homeostasis of metabolic processes. Past and current experience with GERM linking rules is presented in order to point-out how optimized globally efficient kinetic models for the genetic regulatory circuits (GRC) can be obtained to reproduce experimental observations. Based on quantitative regulatory indices evaluated vs. simulated dynamic and stationary environmental perturbations, the paper exemplifies with GERM-s from E. coli, at a generic level, how this methodology can be extended to characterize the GERM module efficiency, species connectivity, and system stability.
Keywords: kinetic modelling of cell protein synthesis; homeostatic regulation; gene expression regulatory modules (GERM); linking GERM-s