Imperial College London

Professor Kitney

Faculty of EngineeringDepartment of Bioengineering

Professor of BioMedical Systems Engineering
 
 
 
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Contact

 

+44 (0)20 7594 6226r.kitney Website

 
 
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Assistant

 

Ms Tania Briggs +44 (0)20 7594 6226

 
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Location

 

3.16Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wong:2015:10.1186/s12915-015-0146-0,
author = {Wong, A and Wang, H and Poh, CL and Kitney, RI},
doi = {10.1186/s12915-015-0146-0},
journal = {BMC Biology},
title = {Layering genetic circuits to build a single cell, bacterial half adder},
url = {http://dx.doi.org/10.1186/s12915-015-0146-0},
volume = {13},
year = {2015}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Background: Gene regulation in biological systems is impacted by the cellular and genetic context-dependenteffects of the biological parts which comprise the circuit. Here, we have sought to elucidate the limitations ofengineering biology from an architectural point of view, with the aim of compiling a set of engineering solutionsfor overcoming failure modes during the development of complex, synthetic genetic circuits.Results: Using a synthetic biology approach that is supported by computational modelling and rigorouscharacterisation, AND, OR and NOT biological logic gates were layered in both parallel and serial arrangements togenerate a repertoire of Boolean operations that include NIMPLY, XOR, half adder and half subtractor logics in asingle cell. Subsequent evaluation of these near-digital biological systems revealed critical design pitfalls thattriggered genetic context-dependent effects, including 5′ UTR interferences and uncontrolled switch-on behaviourof the supercoiled σ54 promoter. In particular, the presence of seven consecutive hairpins immediately downstreamof the promoter transcription start site severely impeded gene expression.Conclusions: As synthetic biology moves forward with greater focus on scaling the complexity of engineeredgenetic circuits, studies which thoroughly evaluate failure modes and engineering solutions will serve as importantreferences for future design and development of synthetic biological systems. This work describes a representativecase study for the debugging of genetic context-dependent effects through principles elucidated herein, therebyproviding a rational design framework to integrate multiple genetic circuits in a single prokaryotic cell.
AU - Wong,A
AU - Wang,H
AU - Poh,CL
AU - Kitney,RI
DO - 10.1186/s12915-015-0146-0
PY - 2015///
SN - 1741-7007
TI - Layering genetic circuits to build a single cell, bacterial half adder
T2 - BMC Biology
UR - http://dx.doi.org/10.1186/s12915-015-0146-0
UR - http://hdl.handle.net/10044/1/25677
VL - 13
ER -