Evidence map›Paper›PMID 26078033›Full record

ArticleBMC biology2015

Layering genetic circuits to build a single cell, bacterial half adder.

Adison Wong, Huijuan Wang, Chueh Loo Poh, Richard I Kitney

Open access · goldAbstract read
In one paragraph

Article in BMC biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

22 citing papers in PubMed, 54 citations in OpenAlex.

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  11. Cellular Computational Logic Using Toehold Switches.International journal of molecular sciences · 2022
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  20. Synthesis of control unit for future biocomputer.Journal of biological engineering · 2018
    Article
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

4 authors at 3 institutions in 2 countries.

Adison WongDivision of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637459, Singapore.
Huijuan WangDivision of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637459, Singapore.
Chueh Loo PohDivision of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637459, Singapore. clpoh@ntu.edu.sg.
Richard I KitneyCentre for Synthetic Biology and Innovation, and Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK. r.kitney@imperial.ac.uk.
Imperial College London · GBNanyang Technological University · SGNational University of Singapore · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGene regulation in biological systems is impacted by the cellular and genetic context-dependent effects of the biological parts which comprise the circuit. Here, we have sought to elucidate the limitations of engineering biology from an architectural point of view, with the aim of compiling a set of engineering solutions for overcoming failure modes during the development of complex, synthetic genetic circuits.

resultsUsing a synthetic biology approach that is supported by computational modelling and rigorous characterisation, AND, OR and NOT biological logic gates were layered in both parallel and serial arrangements to generate a repertoire of Boolean operations that include NIMPLY, XOR, half adder and half subtractor logics in a single cell. Subsequent evaluation of these near-digital biological systems revealed critical design pitfalls that triggered genetic context-dependent effects, including 5' UTR interferences and uncontrolled switch-on behaviour of the supercoiled σ54 promoter. In particular, the presence of seven consecutive hairpins immediately downstream of the promoter transcription start site severely impeded gene expression.

conclusionsAs synthetic biology moves forward with greater focus on scaling the complexity of engineered genetic circuits, studies which thoroughly evaluate failure modes and engineering solutions will serve as important references for future design and development of synthetic biological systems. This work describes a representative case study for the debugging of genetic context-dependent effects through principles elucidated herein, thereby providing a rational design framework to integrate multiple genetic circuits in a single prokaryotic cell.

Indexed as

Computers, MolecularGene Regulatory Networks5' Untranslated RegionsEscherichia coliPromoter Regions, GeneticSynthetic Biology5' Untranslated Regions

Identifiers

PMID26078033
PMCPMC4490610
OpenAlexW1566904010

What OpenQuestion holds

Textmetadata
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.