Please use this identifier to cite or link to this item: https://doi.org/10.1186/s12915-015-0146-0
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dc.titleLayering genetic circuits to build a single cell, bacterial half adder
dc.contributor.authorWong, A
dc.contributor.authorWang, H
dc.contributor.authorPoh, C.L
dc.contributor.authorKitney, R.I
dc.date.accessioned2020-09-03T10:34:38Z
dc.date.available2020-09-03T10:34:38Z
dc.date.issued2015
dc.identifier.citationWong, A, Wang, H, Poh, C.L, Kitney, R.I (2015). Layering genetic circuits to build a single cell, bacterial half adder. BMC Biology 13 (1) : 40. ScholarBank@NUS Repository. https://doi.org/10.1186/s12915-015-0146-0
dc.identifier.issn17417007
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174125
dc.description.abstractBackground: Gene 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. Results: Using 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 ?54 promoter. In particular, the presence of seven consecutive hairpins immediately downstream of the promoter transcription start site severely impeded gene expression. Conclusions: As 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. © 2015 Wong et al.
dc.sourceUnpaywall 20200831
dc.subjectBacteria (microorganisms)
dc.subjectProkaryota
dc.subject5' untranslated region
dc.subject5' untranslated region
dc.subjectEscherichia coli
dc.subjectgene regulatory network
dc.subjectgenetics
dc.subjectmolecular computer
dc.subjectprocedures
dc.subjectpromoter region
dc.subjectsynthetic biology
dc.subject5' Untranslated Regions
dc.subjectComputers, Molecular
dc.subjectEscherichia coli
dc.subjectGene Regulatory Networks
dc.subjectPromoter Regions, Genetic
dc.subjectSynthetic Biology
dc.typeArticle
dc.contributor.departmentBIOMEDICAL ENGINEERING
dc.description.doi10.1186/s12915-015-0146-0
dc.description.sourcetitleBMC Biology
dc.description.volume13
dc.description.issue1
dc.description.page40
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