Lumped dynamic model for a bistable genetic regulatory circuit within a variable-volume whole-cell modelling framework

✍ Scribed by Gheorghe Maria

• Publisher: Wiley (John Wiley & Sons)
• Year: 2009
• Tongue: English
• Weight: 296 KB
• Volume: 4
• Category: Article
• ISSN: 1932-2135
• DOI: 10.1002/apj.297

✦ Synopsis

Abstract

Genetic regulatory circuits (GRCs) including switches, oscillators, signal amplifiers or filters, and signalling circuits are responsible for the control of cell metabolism. Modelling such complex GRCs is a difficult task due to high complexity of the the process (partly known) and the structural, functional and temporal hierarchical organisation of the cell system. Modular lumped representation, grouping some reactions/components and including different types of variables, is a promising alternative allowing individual module characterisation and elaboration of extended simulation platforms for representing the GRC dynamic properties and designing new cell functions. Such models allow to in‐silico design modified micro‐organisms with desirable properties for practical applications in bioprocess engineering and biotechnology. In the present work, the analysis of a designed bistable switch formed by two gene expression modules is performed in a variable‐volume and whole‐cell modelling framework, by mimicking the Escherichia coli cell growth. The advantages but also limitations of such a new approach are investigated, by using a Hill‐type kinetics combined with few elementary steps, with the aim of better representing the adjustable levels of key intermediates tuning the GRC regulatory properties in terms of stability strength, species connectivity, responsiveness, and regulatory efficiency under stationary and dynamic perturbations. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd.