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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:2012:nar/gkr905,
author = {Silhan, J and Nagorska, K and Zhao, Q and Jensen, K and Freemont, PS and Tang, CM and Baldwin, GS},
doi = {nar/gkr905},
journal = {Nucleic Acids Research},
pages = {2065--2075},
title = {Specialization of an Exonuclease III family enzyme in the repair of 3' DNA lesions during base excision repair in the human pathogen Neisseria meningitidis},
url = {http://dx.doi.org/10.1093/nar/gkr905},
volume = {40},
year = {2012}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - We have previously demonstrated that the twoExonuclease III (Xth) family members presentwithin the obligate human pathogen Neisseriameningitidis, NApe and NExo, are important forsurvival under conditions of oxidative stress. Ofthese, only NApe possesses AP endonucleaseactivity, while the primary function of NExoremained unclear. We now reveal further functionalspecialization at the level of 30-PO4 processing forNExo. We demonstrate that the bi-functional meningococcalglycosylases Nth and MutM can performstrand incisions at abasic sites in addition to NApe.However, no such functional redundancy existsfor the 30-phosphatase activity of NExo, and thecytotoxicity of 30-blocking lesions is reflectedin the marked sensitivity of a mutant lackingNExo to oxidative stress, compared to strainsdeficient in other base excision repair enzymes. Ahistidine residue within NExo that is responsiblefor its lack of AP endonuclease activity isalso important for its 30-phosphatase activity,demonstrating an evolutionary trade off in enzymefunction at the single amino acid level. This specializationof two Xth enzymes for the 30-end processingand strand-incision reactions has notpreviously been observed and provides a newparadigm within the prokaryotic world for separationof these critical functions during baseexcision repair.
AU  - Silhan,J
AU  - Nagorska,K
AU  - Zhao,Q
AU  - Jensen,K
AU  - Freemont,PS
AU  - Tang,CM
AU  - Baldwin,GS
DO  - nar/gkr905
EP  - 2075
PY  - 2012///
SN  - 1362-4962
SP  - 2065
TI  - Specialization of an Exonuclease III family enzyme in the repair of 3' DNA lesions during base excision repair in the human pathogen Neisseria meningitidis
T2  - Nucleic Acids Research
UR  - http://dx.doi.org/10.1093/nar/gkr905
UR  - http://hdl.handle.net/10044/1/26423
VL  - 40
ER  -