Synthetic negative feedback circuits using engineered small RNAs

Nucleic Acids Research
Ciarán L KellyAntonis Papachristodoulou

Abstract

Negative feedback is known to enable biological and man-made systems to perform reliably in the face of uncertainties and disturbances. To date, synthetic biological feedback circuits have primarily relied upon protein-based, transcriptional regulation to control circuit output. Small RNAs (sRNAs) are non-coding RNA molecules that can inhibit translation of target messenger RNAs (mRNAs). In this work, we modelled, built and validated two synthetic negative feedback circuits that use rationally-designed sRNAs for the first time. The first circuit builds upon the well characterised tet-based autorepressor, incorporating an externally-inducible sRNA to tune the effective feedback strength. This allows more precise fine-tuning of the circuit output in contrast to the sigmoidal, steep input-output response of the autorepressor alone. In the second circuit, the output is a transcription factor that induces expression of an sRNA, which inhibits translation of the mRNA encoding the output, creating direct, closed-loop, negative feedback. Analysis of the noise profiles of both circuits showed that the use of sRNAs did not result in large increases in noise. Stochastic and deterministic modelling of both circuits agreed well with experim...Continue Reading

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Citations

Nov 18, 2018·Nucleic Acids Research·Charles E CookRolf Apweiler
Jul 31, 2020·PLoS Biology·Harrison SteelAntonis Papachristodoulou
Dec 24, 2018·Nature Communications·Hsin-Ho HuangDomitilla Del Vecchio
Aug 4, 2020·ELife·Mona HoyosKai Papenfort
Dec 19, 2019·Nature Communications·Deepak K AgrawalEduardo D Sontag
May 1, 2020·Nature Communications·Vittorio BartoliThomas E Gorochowski
Dec 13, 2018·Nucleic Acids Research·Xuedong ZhengXiaopeng Wei
Feb 5, 2021·Cell Systems·Christian Cuba Samaniego, Elisa Franco
Feb 10, 2021·Nature Communications·Rong ZhangXiao-Jun Tian
Mar 21, 2021·Nature Communications·F Veronica GrecoThomas E Gorochowski
Jun 9, 2021·Nature Communications·Simeon D CastleThomas E Gorochowski
Jun 2, 2021·Current Opinion in Microbiology·Giansimone PerrinoGuy-Bart Stan
Sep 11, 2019·ACS Synthetic Biology·Harrison Steel, Antonis Papachristodoulou
Sep 14, 2021·Metabolic Engineering·Milca Rachel da Costa Ribeiro LinsDanielle Biscaro Pedrolli
Dec 21, 2021·IScience·Emmanouil AlexisAntonis Papachristodoulou

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Datasets Mentioned

BETA
MH822874
MH822880

Methods Mentioned

BETA
flow cytometry

Software Mentioned

MATLAB
IntaRNA

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