title: Experimental measurements and mathematical modeling of biological noise arising from transcriptional and translational regulation of basic synthetic gene circuits.
abstract: The small number of molecules, unevenly distributed within an isogenic cell population, makes gene expression a noisy process, and strategies have evolved to deal with this variability in protein concentration and to limit its impact on cellular behaviors. As translational efficiency has a major impact on biological noise, a possible strategy to control noise is to regulate gene expression processes at the post-transcriptional level. In this study, fluctuations in the concentration of a green fluorescent protein were compared, at the single cell level, upon transformation of an isogenic bacterial cell population with synthetic gene circuits implementing either a transcriptional or a post-transcriptional control of gene expression. Experimental measurements showed that protein variability is lower under post-transcriptional control, when the same average protein concentrations are compared. This effect is well reproduced by stochastic simulations, supporting the hypothesis that noise reduction is due to the control mechanism acting on the efficiency of translation. Similar strategies are likely to play a role in noise reduction in natural systems and to be useful for controlling noise in synthetic biology applications.
authors.affiliation: Laboratory of Cellular and Molecular Engineering "S. Cavalcanti", Department of Electrical, Electronic and Information Engineering "G. Marconi" (DEI), University of Bologna, Cesena, Italy. Electronic address: lucia.bandiera2@unibo.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Bandiera
authors.affiliation: Laboratory of Cellular and Molecular Engineering "S. Cavalcanti", Department of Electrical, Electronic and Information Engineering "G. Marconi" (DEI), University of Bologna, Cesena, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Pasini
authors.affiliation: Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy; Centre for Health Technologies, University of Pavia, Pavia, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pasotti
authors.affiliation: Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy; Centre for Health Technologies, University of Pavia, Pavia, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Zucca
authors.affiliation: Institute of Molecular Genetics CNR, Pavia, Italy; Department "L. Spallanzani", University of Pavia, Pavia, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Mazzini
authors.affiliation: Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy; Centre for Health Technologies, University of Pavia, Pavia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Magni
authors.affiliation: Laboratory of Cellular and Molecular Engineering "S. Cavalcanti", Department of Electrical, Electronic and Information Engineering "G. Marconi" (DEI), University of Bologna, Cesena, Italy; BioEngLab, Health Science and Technology, Interdepartmental Center for Industrial Research (HST-CIRI), University of Bologna, Ozzano Emilia, Italy; Advanced Research Center on Electronic Systems (ARCES), University of Bologna, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Giordano
authors.affiliation: Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Furini
mesh_terms: D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000096:biosynthesis*; D053263:Gene Regulatory Networks / Q000502:physiology*; D008954:Models, Biological; D014176:Protein Biosynthesis / Q000502:physiology*; D059629:Signal-To-Noise Ratio; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D029968:Escherichia coli Proteins
keywords: Gene-expression noise; Post-transcriptional regulation; Stochastic simulations; Synthetic biology