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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{Silhan:2018:nar/gky934,
author = {Silhan, J and Zhao, Q and Boura, E and Thomson, H and Förster, A and Tang, CM and Freemont, PS and Baldwin, GS},
doi = {nar/gky934},
journal = {Nucleic Acids Research},
pages = {11980--11989},
title = {Structural basis for recognition and repair of the 3'-phosphate by NExo, a base excision DNA repair nuclease from Neisseria meningitidis},
url = {http://dx.doi.org/10.1093/nar/gky934},
volume = {46},
year = {2018}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - NExo is an enzyme from Neisseria meningitidis that is specialized in the removal of the 3'-phosphate and other 3'-lesions, which are potential blocks for DNA repair. NExo is a highly active DNA 3'-phosphatase, and although it is from the class II AP family it lacks AP endonuclease activity. In contrast, the NExo homologue NApe, lacks 3'-phosphatase activity but is an efficient AP endonuclease. These enzymes act together to protect the meningococcus from DNA damage arising mainly from oxidative stress and spontaneous base loss. In this work, we present crystal structures of the specialized 3'-phosphatase NExo bound to DNA in the presence and absence of a 3'-phosphate lesion. We have outlined the reaction mechanism of NExo, and using point mutations we bring mechanistic insights into the specificity of the 3'-phosphatase activity of NExo. Our data provide further insight into the molecular origins of plasticity in substrate recognition for this class of enzymes. From this we hypothesize that these specialized enzymes lead to enhanced efficiency and accuracy of DNA repair and that this is important for the biological niche occupied by this bacterium.
AU  - Silhan,J
AU  - Zhao,Q
AU  - Boura,E
AU  - Thomson,H
AU  - Förster,A
AU  - Tang,CM
AU  - Freemont,PS
AU  - Baldwin,GS
DO  - nar/gky934
EP  - 11989
PY  - 2018///
SN  - 0305-1048
SP  - 11980
TI  - Structural basis for recognition and repair of the 3'-phosphate by NExo, a base excision DNA repair nuclease from Neisseria meningitidis
T2  - Nucleic Acids Research
UR  - http://dx.doi.org/10.1093/nar/gky934
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30329088
UR  - http://hdl.handle.net/10044/1/65533
VL  - 46
ER  -