Please use this identifier to cite or link to this item:
DC FieldValue
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.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.
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.subject5' untranslated region
dc.subject5' untranslated region
dc.subjectEscherichia coli
dc.subjectgene regulatory network
dc.subjectmolecular computer
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.contributor.departmentBIOMEDICAL ENGINEERING
dc.description.sourcetitleBMC Biology
Appears in Collections:Elements
Staff Publications

Show simple item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1186_s12915-015-0146-0.pdf2.72 MBAdobe PDF




checked on Nov 22, 2020

Page view(s)

checked on Nov 27, 2020

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.