Engineered control of genetic variability reveals interplay between quorum sensing, feedback regulation and biochemical noise

TitleEngineered control of genetic variability reveals interplay between quorum sensing, feedback regulation and biochemical noise
Publication TypeJournal Article
Year of Publication2017
AuthorsBoada Y, Vignoni A, Picó J
JournalACS Synthetic Biology
Abstract

Stochastic fluctuations in gene expression trigger both beneficial and harmful con- sequences for cell behavior. Therefore, achieving a desired mean protein expression level while minimizing noise is of interest in many applications, including robust pro- tein production systems in industrial biotechnology. Here we consider a synthetic gene circuit combining intracellular negative feedback and cell-to-cell communication based on quorum sensing. Accounting for both intrinsic and extrinsic noise, stochastic sim- ulations allow us to analyze the capability of the circuit to reduce noise strength as a function of its parameters. We obtain mean expression level and noise strength for all species under different scenarios showing good agreement with system-wide available experimental data of protein abundance and noise in E. coli. Our in silico experiments, validated by preliminary in vivo results, reveal significant noise attenuation in gene expression through the interplay between quorum sensing and negative feedback, and highlight the differential role they play in regard to intrinsic and extrinsic noise. 

DOI10.1021/acssynbio.7b00087