Mini Review
Volume 1 Issue 4 - February 2017
Curr Trends Biomedical Eng & Biosci
Copyright © All rights are reserved by Gheorghe Maria
Application of (bio) chemical engineering principles
and lumping analysis in modelling
the living systems
Gheorghe Maria*
Department of Chemical & Biochemical Engineering, University Politehnica of Bucharest, Romania
Submission: February 07, 2017; Published: February 10, 2017
*Corresponding author: Gheorghe Maria, Department of Chemical & Biochemical Engineering, Politehnica University of Bucharest, Splaiul
Independenței 313, București 060042, Romania, Email:
Introduction
Living cells are organized, self-replicating, self-adjustable,
evolvable and responsive structures to environmental stimuli.
Attempts to model metabolic cell reactions and processes are
not new, an adequate dynamic model being the one engineering
alternative to coherently, consistently, and systematically in-
silico represent the cell metabolism aiming at studying the
cell response to various perturbations (reviews [5,6,8,17,18]).
Thus, Synthetic Biology and System Biology become emergent
sciences focus on the engineering-driven model-based building
of complex biological entities, aiming at applying engineering
principles of systems design to biology with the idea to produce
predictable and robust biological systems with novel functions
in a broad area of applications, such as therapy of diseases (gene
therapy), design of new biotechnological processes, new devices
based on cell-cell communicators, biosensors, etc. “System
Biology can be defined as “the science of discovering, modelling,
understanding and ultimately engineering at the molecular level
the dynamic relationships between the biological molecules that
define living organisms.” (Leroy Hood, President Institute for
System Biology, Seattle, USA, cited by [17,18]).
Due to the highly complex and partly unknown aspects of
the metabolic processes, the detailed mathematical modelling
at a molecular level remains still an unsettled issue, even
if remarkable progresses and developments of extended
simulation platforms have been reported. The general modelling
rules, based on physico-chemical-biological and chemical
engineering principles, and a statistical data treatment are
more difficult to be applied to living systems. That is because
metabolic cell processes present a low observability vs. the very
large number of species of the order O(10
4
), reactions O(10
5
),
Current Trends in Biomedical
Engineering & Biosciences
Curr Trends Biomedical Eng & Biosci 1(4): CTBEB.MS.ID.555566 (2017) 001
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.
Keywords: Kinetic modelling of cell metabolic processes; Homeostatic regulation of gene expression; Regulatory modules of gene expression
(GERM); Linking GERM-s