Modelling the burden caused by gene expression: an in silico investigation into the interactions between synthetic gene circuits and their chassis cell

In this paper we motivate and develop a model of gene expression for the purpose of studying the interaction between synthetic gene circuits and the chassis cell within which they are in- serted. This model focuses on the translational aspect of gene expression as this is where the literature suggests the crucial interaction between gene expression and shared resources lies.

[1]  Barbara M. Bakker,et al.  How Molecular Competition Influences Fluxes in Gene Expression Networks , 2011, PloS one.

[2]  J. H. Gibbs,et al.  Concerning the kinetics of polypeptide synthesis on polyribosomes , 1969 .

[3]  Kim Sneppen,et al.  Ribosome collisions and translation efficiency: optimization by codon usage and mRNA destabilization. , 2008, Journal of molecular biology.

[4]  D. Chowdhury,et al.  Traffic of interacting ribosomes: effects of single-machine mechanochemistry on protein synthesis. , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[5]  J E Bailey,et al.  Simulations of host–plasmid interactions in Escherichia coli: Copy number, promoter strength, and ribosome binding site strength effects on metabolic activity and plasmid gene expression , 1987, Biotechnology and bioengineering.

[6]  G. Dougan,et al.  Cooperation Between Translating Ribosomes and RNA Polymerase in Transcription Elongation , 2010, Science.

[7]  M. Sørensen,et al.  Synthesis of proteins in Escherichia coli is limited by the concentration of free ribosomes. Expression from reporter genes does not always reflect functional mRNA levels. , 1993, Journal of molecular biology.

[8]  T. Hwa,et al.  Interdependence of Cell Growth and Gene Expression: Origins and Consequences , 2010, Science.

[9]  J E Bailey,et al.  Mechanistically detailed model of cellular metabolism for glucose‐limited growth of Escherichia coli B/r‐A , 1986, Biotechnology and bioengineering.

[10]  T. Chou,et al.  Clustered bottlenecks in mRNA translation and protein synthesis. , 2003, Physical review letters.

[11]  T. Hwa,et al.  Growth Rate-Dependent Global Effects on Gene Expression in Bacteria , 2009, Cell.

[12]  Jörg Stelling,et al.  Computational design of synthetic gene circuits with composable parts , 2008, Bioinform..

[13]  L. You,et al.  Emergent bistability by a growth-modulating positive feedback circuit. , 2009, Nature chemical biology.

[14]  Naama Barkai,et al.  Coordination of gene expression with growth rate: A feedback or a feed‐forward strategy? , 2009, FEBS letters.