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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{Gowers:2019:10.1021/acssynbio.9b00243,
author = {Gowers, G-OF and Cameron, SJS and Perdones-Montero, A and Bell, D and Chee, SM and Kern, M and Tew, D and Ellis, T and Takats, Z},
doi = {10.1021/acssynbio.9b00243},
journal = {ACS Synthetic Biology},
pages = {2566--2575},
title = {Off-colony screening of biosynthetic libraries by rapid laser-enabled mass spectrometry},
url = {http://dx.doi.org/10.1021/acssynbio.9b00243},
volume = {8},
year = {2019}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Leveraging advances in DNA synthesis and molecular cloning techniques, synthetic biology increasingly makes use of large construct libraries to explore large design spaces. For biosynthetic pathway engineering the ability to screen these libraries for a variety of metabolites of interest is essential. If the metabolite of interest or the metabolic phenotype is not easily measurable, screening soon becomes a major bottleneck involving time-consuming culturing, sample preparation, and extraction. To address this, we demonstrate the use of automated Laser-Assisted Rapid Evaporative Ionisation Mass Spectrometry (LA-REIMS) - a form of ambient laser desorption ionisation mass spectrometry - to perform rapid mass spectrometry analysis direct from agar plate yeast colonies without sample preparation or extraction. We use LA-REIMS to assess production levels of violacein and betulinic acid directly from yeast colonies at a rate of 6 colonies per minute. We then demonstrate the throughput enabled by LA-REIMS by screening over 450 yeast colonies in under 4 hours, while simultaneously generating recoverable glycerol stocks of each colony in real-time. This showcases LA-REIMS as a pre-screening tool to complement downstream quantification methods such as LCMS. Through pre-screening several hundred colonies with LA-REIMS, we successfully isolate and verify a strain with a 2.5-fold improvement in betulinic acid production. Finally, we show that LA-REIMS can detect 20 out of a panel of 27 diverse biological molecules, demonstrating the broad applicability of LA-REIMS to metabolite detection. The rapid and automated nature of LA-REIMS makes this a valuable new technology to complement existing screening technologies currently employed in academic and industrial workflows.
AU  - Gowers,G-OF
AU  - Cameron,SJS
AU  - Perdones-Montero,A
AU  - Bell,D
AU  - Chee,SM
AU  - Kern,M
AU  - Tew,D
AU  - Ellis,T
AU  - Takats,Z
DO  - 10.1021/acssynbio.9b00243
EP  - 2575
PY  - 2019///
SN  - 2161-5063
SP  - 2566
TI  - Off-colony screening of biosynthetic libraries by rapid laser-enabled mass spectrometry
T2  - ACS Synthetic Biology
UR  - http://dx.doi.org/10.1021/acssynbio.9b00243
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31622554
UR  - https://pubs.acs.org/doi/10.1021/acssynbio.9b00243
UR  - http://hdl.handle.net/10044/1/74295
VL  - 8
ER  -