Engineering Stochasticity in Gene Expression
Overview
Molecular Biology
Affiliations
Stochastic fluctuations (noise) in gene expression can cause members of otherwise genetically identical populations to display drastically different phenotypes. An understanding of the sources of noise and the strategies cells employ to function reliably despite noise is proving to be increasingly important in describing the behavior of natural organisms and will be essential for the engineering of synthetic biological systems. Here we describe the design of synthetic constructs, termed ribosome competing RNAs (rcRNAs), as a means to rationally perturb noise in cellular gene expression. We find that noise in gene expression increases in a manner proportional to the ability of an rcRNA to compete for the cellular ribosome pool. We then demonstrate that operons significantly buffer noise between coexpressed genes in a natural cellular background and can even reduce the level of rcRNA enhanced noise. These results demonstrate that synthetic genetic constructs can significantly affect the noise profile of a living cell and, importantly, that operons are a facile genetic strategy for buffering against noise.
Principles for the design of multicellular engineered living systems.
Aydin O, Passaro A, Raman R, Spellicy S, Weinberg R, Kamm R APL Bioeng. 2022; 6(1):010903.
PMID: 35274072 PMC: 8893975. DOI: 10.1063/5.0076635.
Robust Synthetic Circuits for Two-Dimensional Control of Gene Expression in Yeast.
Aranda-Diaz A, Mace K, Zuleta I, Harrigan P, El-Samad H ACS Synth Biol. 2016; 6(3):545-554.
PMID: 27930885 PMC: 5507677. DOI: 10.1021/acssynbio.6b00251.
How to train your microbe: methods for dynamically characterizing gene networks.
Castillo-Hair S, Igoshin O, Tabor J Curr Opin Microbiol. 2015; 24:113-23.
PMID: 25677419 PMC: 4380544. DOI: 10.1016/j.mib.2015.01.008.
Almagro G, Viale A, Montero M, Rahimpour M, Munoz F, Baroja-Fernandez E PLoS One. 2015; 10(1):e0115516.
PMID: 25607991 PMC: 4301808. DOI: 10.1371/journal.pone.0115516.
A 'resource allocator' for transcription based on a highly fragmented T7 RNA polymerase.
Segall-Shapiro T, Meyer A, Ellington A, Sontag E, Voigt C Mol Syst Biol. 2014; 10:742.
PMID: 25080493 PMC: 4299498. DOI: 10.15252/msb.20145299.