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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{Ceroni:2018:10.1038/nmeth.4635,
author = {Ceroni, F and Boo, A and Furini, S and Gorochowski, T and Ladak, Y and Awan, A and Gilbert, C and Stan, G and Ellis, T},
doi = {10.1038/nmeth.4635},
journal = {Nature Methods},
pages = {387--393},
title = {Burden-driven feedback control of gene expression},
url = {http://dx.doi.org/10.1038/nmeth.4635},
volume = {15},
year = {2018}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Cells use feedback regulation to ensure robust growth despite fluctuating demands for resources and differing environmental conditions. However, the expression of foreign proteins from engineered constructs is an unnatural burden that cells are not adapted for. Here we combined RNA-seq with an in vivo assay to identify the major transcriptional changes that occur in Escherichia coli when inducible synthetic constructs are expressed. We observed that native promoters related to the heat-shock response activated expression rapidly in response to synthetic expression, regardless of the construct. Using these promoters, we built a dCas9-based feedback-regulation system that automatically adjusts the expression of a synthetic construct in response to burden. Cells equipped with this general-use controller maintained their capacity for native gene expression to ensure robust growth and thus outperformed unregulated cells in terms of protein yield in batch production. This engineered feedback is to our knowledge the first example of a universal, burden-based biomolecular control system and is modular, tunable and portable.
AU  - Ceroni,F
AU  - Boo,A
AU  - Furini,S
AU  - Gorochowski,T
AU  - Ladak,Y
AU  - Awan,A
AU  - Gilbert,C
AU  - Stan,G
AU  - Ellis,T
DO  - 10.1038/nmeth.4635
EP  - 393
PY  - 2018///
SN  - 1548-7091
SP  - 387
TI  - Burden-driven feedback control of gene expression
T2  - Nature Methods
UR  - http://dx.doi.org/10.1038/nmeth.4635
UR  - https://www.nature.com/articles/nmeth.4635
UR  - http://hdl.handle.net/10044/1/57105
VL  - 15
ER  -