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Research

Biological systems - including the simplest cells - exhibit a broad range of functions to thrive in their environment. Research in the Imperial College Centre for Synthetic Biology is focused on the possibility of engineering the underlying biochemical processes to solve many of the challenges facing society, from healthcare to sustainable energy. In particular, we model, analyse, design and build biological and biochemical systems in living cells and/or in cell extracts, both exploring and enhancing the engineering potential of biology.

As part of our research we develop novel methods to accelerate the celebrated Design-Build-Test-Learn synthetic biology cycle. As such research in the Centre for Synthetic Biology highly multi- and interdisciplinary covering computational modelling and machine learning approaches; automated platform development and genetic circuit engineering ; multi-cellular and multi-organismal interactions, including gene drive and genome engineering; metabolic engineering; in vitro/cell-free synthetic biology; engineered phages and directed evolution; and biomimetics, biomaterials and biological engineering.

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}
}

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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  -

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