Research

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Synthetic Biology underpins advances in the bioeconomy

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{Wood:2019:10.1016/j.celrep.2019.08.094,
author = {Wood, TE and Howard, SA and Forster, A and Nolan, LM and Manoli, E and Bullen, NP and Yau, HCL and Hachani, A and Hayward, RD and Whitney, JC and Vollmer, W and Freemont, PS and Filloux, A},
doi = {10.1016/j.celrep.2019.08.094},
journal = {Cell Reports},
pages = {187--201.e7},
title = {The Pseudomonas aeruginosa T6SS delivers a periplasmic toxin that disrupts bacterial cell morphology},
url = {http://dx.doi.org/10.1016/j.celrep.2019.08.094},
volume = {29},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The  type  VI  secretion  system  (T6SS) is crucialin  interbacterial  competition and is avirulence determinant ofmany Gram-negative bacteria. Several T6SS effectorsarecovalently fused to secreted T6SS  structural  components  such  asthe VgrG spike for delivery  into  target  cells.In Pseudomonas aeruginosa, theVgrG2b effector waspreviously proposedto mediatebacterial internalisation into eukaryotic cells. In this work, wefind that the VgrG2b C-terminal domain(VgrG2bC-ter) elicits toxicity in  the  bacterial  periplasm,  counteracted by a  cognate  immunity  protein.We  resolve  thestructure  of VgrG2bC-ter and confirm it is a member ofthezinc-metallopeptidasefamily of enzymes. We show that this effector causesmembrane blebbing atmidcell, whichsuggests a distincttype of T6SS-mediated growthinhibition through interference with cell division, mimicking the impact of β-lactam antibiotics. Ourstudyintroduces a further effector family to the T6SS arsenaland demonstrates that VgrG2b can target both prokaryotic and eukaryotic cells.
AU  - Wood,TE
AU  - Howard,SA
AU  - Forster,A
AU  - Nolan,LM
AU  - Manoli,E
AU  - Bullen,NP
AU  - Yau,HCL
AU  - Hachani,A
AU  - Hayward,RD
AU  - Whitney,JC
AU  - Vollmer,W
AU  - Freemont,PS
AU  - Filloux,A
DO  - 10.1016/j.celrep.2019.08.094
EP  - 201
PY  - 2019///
SN  - 2211-1247
SP  - 187
TI  - The Pseudomonas aeruginosa T6SS delivers a periplasmic toxin that disrupts bacterial cell morphology
T2  - Cell Reports
UR  - http://dx.doi.org/10.1016/j.celrep.2019.08.094
UR  - https://www.sciencedirect.com/science/article/pii/S2211124719311568?via%3Dihub
UR  - http://hdl.handle.net/10044/1/73329
VL  - 29
ER  -
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