Mini Review Volume 18 Issue 3 - February 2019 DOI: 10.19080/CTBEB.2019.18.555988 Curr Trends Biomedical Eng & Biosci Copyright © All rights are reserved by Gheorghe Maria Model-Based Re-Design of some Genetic Regulato- ry Circuits to get Genetic Modified Micro-organisms (GMO) by using Engineering Computational Tools Gheorghe Maria 1 *, Cristiana Luminita Gijiu 1 , Mara Crisan 1 , Cristina Maria 2 and Carmen Tociu 2 1 Department of Chemical and Biochemical Engineering, University Politehnica of Bucharest, Romania 2 National Institute for Research and Development in Environmental Protection, Romania Submission: January 22, 2019; Published: February 20, 2019 *Corresponding author: Gheorghe Maria, Department of Chemical and Biochemical Engineering, University Politehnica of Bucharest, Polizu Str. 1-7, 011061, Bucharest, Romania Curr Trends Biomedical Eng & Biosci 18(3): CTBEB.MS.ID.555988 (2019) 0061 Short Considerations The work is a systematized and reasonable short review of the main published contributions of Dr. Maria in the field of metabolic processes simulation related to the central carbon metabolism (CCM) and modelling the dynamics of the gene expression regulation (GERM) and of the genetic regulation circuits (GRC) in living cells. Application of biochemical engineering, and of nonlinear system control principles and concepts to the modeling of complex cellular processes on deterministic bases are briefly presented with including a rich list of references. These models are essential for understanding and simulating the CCM, useful to in-silico (that is model-based) re-design of genetically modified micro-organisms (GMOs) with applications in industrial biosynthesis, medicine, environmental engineering, vaccine production, biosensors, etc. A special attention is paid to authors’ contributions related to dynamics simulation of the gene expression regulatory modules (GERM) and of genetic regulation circuits (GRC) in living cells, by promoting novel concepts of a novel cell modelling framework, that is the so-called “variable-volume- whole-cell” (VVWC) models. The relatively novel concept of” whole-cell” simulation of cell metabolic processes has been reviewed to prove its advantages when building-up dynamic models of modular structures that can reproduce complex metabolic syntheses inside living cells. The advantages of the more realistic VVWC approach are briefly underlined and exemplified when developing kinetic representations of the gene expression regulatory modules (GERM) that control the protein synthesis and homeostasis of metabolic processes. After a brief presentation of the general concepts and particularities of the VVWC modelling, both past and current experience with constructing effective GERM models is reviewed, together with some rules used when linking GERM-s to build-up models for optimized globally efficient genetic regulatory circuits (GRC), by using quantified regulatory indices evaluated vs. simulated dynamic and stationary environmental perturbations. The topics belongs to the emergent field of Systems Biology, 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, Inst. Systems Biology, Seattle). Systems Biology is one of the modern tools, which uses advanced mathematical simulation models for in-silico re-design of GMOs that possess specific and desired functions and characteristics. The present work makes a short review of the (bio)chemical engineering principles and deterministic modelling rules used by the Systems Biology for modelling cellular metabolic Abstract The paper is aiming at reviewing the main math modelling and computational tools developed by Maria (2017,2018) [1-3] to in-silico re- design genetic regulation circuits (GRC) in living cells to get GMOs of desired characteristics. A number of suggestive examples (case studies) are mentioned as well. Keywords: Systems biology; Cell metabolism; Deterministic modelling; Gene expression modelling; Genetic regulatory circuits (GRC); Pareto design of E.coli to get maximum succinate; Design cloned E.coli to get maximum mercury uptake; Design E.coli with a genetic switch biosensor; Design E.coli with a desired glycolytic oscillator; Tryptophan synthesis; Glycolytic oscillator Abbrevations: GERM: Gene Expression Regulatory Module; CCM: Central Carbon Metabolism; GRC: Genetic Regulation Circuits; GMOs: Genetically Modified Micro-Organisms; VVWC: Variable-Volume-Whole-Cell; SUCC: Succinate; MINLP: Mixed-Integer Nonlinear Programming