Evidence map›Paper›PMID 30212900›Full record

ArticleNucleic acids research2018

Synthetic negative feedback circuits using engineered small RNAs.

Ciarán L Kelly, Andreas W K Harris, Harrison Steel, Edward J Hancock, John T Heap, Antonis Papachristodoulou

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
4.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 95 citations in OpenAlex.

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  8. Regulation strategies for two-output biomolecular networks.Journal of the Royal Society, Interface · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Ciarán L KellyDepartment of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, UK.
Andreas W K HarrisDepartment of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, UK.
Harrison SteelDepartment of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, UK.
Edward J HancockDepartment of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, UK.
John T HeapImperial College Centre for Synthetic Biology, Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
Antonis PapachristodoulouDepartment of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, UK.
University of Oxford · GBImperial College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 experimental data. Finally, simulations using fitted parameters allowed dynamic attributes of each circuit such as response time and disturbance rejection to be investigated.

Indexed as

Feedback, PhysiologicalEscherichia coliGene Expression RegulationModels, GeneticPlasmidsRepressor ProteinsRNA, BacterialRNA, MessengerRNA, Small UntranslatedRepressor ProteinsRNA, BacterialRNA, MessengerRNA, Small Untranslated

Identifiers

PMID30212900
PMCPMC6182179
OpenAlexW2950135916

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.