Application of (bio) chemical engineering principles and lumping analysis in modelling the living systems

 

Abstract

The ”whole-cell” simulation of cell metabolic processes under considering a variable-volume modelling framework has been reviewed to prove their advantages when building-up modular model structures of simplified form that can reproduce complex protein syntheses inside cells. The more realistic “whole-cell-variable-volume” (VVWC) approach is reviewed when developing modular kinetic representations of the homeostatic gene expression regulatory modules (GERM) that control the protein synthesis and homeostasis of metabolic processes. The paper review the general concepts of the VVWC modelling, while the cited literature includes past and current experience with GERM linking rules 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 reviewed literature exemplifies with GERM -s from E. coil, at a generic level, how this methodology can be extended:

    i) To characterize the module efficiency, species connectivity, and system stability;

    ii) To build-up modular regulatory chains of various complexity;

    iii) To prove feasibility of the cooperative vs. concurrent construction that ensures an efficient gene expression, system homeostasis, proteic functions, and a balanced cell growth during the cell cycle;

    iv) To prove the effect of the whole-cell content ballast in smoothing the effect of internal/external perturbations on the system homeostasis.


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