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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{Deng:2019:10.1016/j.ymben.2019.07.008,
author = {Deng, J and Chen, C and Gu, Y and Lv, X and Liu, Y and Li, J and Ledesma-Amaro, R and Du, G and Liu, L},
doi = {10.1016/j.ymben.2019.07.008},
journal = {Metabolic Engineering},
pages = {179--190},
title = {Creating an in vivo bifunctional gene expression circuit through an aptamer-based regulatory mechanism for dynamic metabolic engineering in Bacillus subtilis.},
url = {http://dx.doi.org/10.1016/j.ymben.2019.07.008},
volume = {55},
year = {2019}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Aptamer-based regulatory biosensors can dynamically regulate the expression of target genes in response to ligands and could be used in dynamic metabolic engineering for pathway optimization. However, the existing aptamer-ligand biosensors can only function with non-complementary DNA elements that cannot replicate in growing cells. Here, we construct an aptamer-based synthetic regulatory circuit that can dynamically upregulate and downregulate the expression of target genes in response to the ligand thrombin at transcriptional and translational levels, respectively, and further used this system to dynamically engineer the synthesis of 2'-fucosyllactose (2'-FL) in Bacillus subtilis. First, we demonstrated the binding of ligand molecule thrombin with the aptamer can induce the unwinding of fully complementary double-stranded DNA. Based on this finding, we constructed a bifunctional gene expression regulatory circuit using ligand thrombin-bound aptamers. The expression of the reporter gene ranged from 0.084- to 48.1-fold. Finally, by using the bifunctional regulatory circuit, we dynamically upregulated the expression of key genes fkp and futC and downregulated the expression of gene purR, resulting in the significant increase of 2'-FL titer from 24.7 to 674mg/L. Compared with the other pathway-specific dynamic engineering systems, here the constructed aptamer-based regulatory circuit is independent of pathways, and can be generally used to fine-tune gene expression in other microbes.
AU  - Deng,J
AU  - Chen,C
AU  - Gu,Y
AU  - Lv,X
AU  - Liu,Y
AU  - Li,J
AU  - Ledesma-Amaro,R
AU  - Du,G
AU  - Liu,L
DO  - 10.1016/j.ymben.2019.07.008
EP  - 190
PY  - 2019///
SN  - 1096-7176
SP  - 179
TI  - Creating an in vivo bifunctional gene expression circuit through an aptamer-based regulatory mechanism for dynamic metabolic engineering in Bacillus subtilis.
T2  - Metabolic Engineering
UR  - http://dx.doi.org/10.1016/j.ymben.2019.07.008
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31336181
UR  - https://www.sciencedirect.com/science/article/pii/S1096717619302186?via%3Dihub
UR  - http://hdl.handle.net/10044/1/73261
VL  - 55
ER  -