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
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Journal articleSilhan J, Nagorska K, Zhao Q, et al., 2012,
Specialization of an Exonuclease III family enzyme in the repair of 3' DNA lesions during base excision repair in the human pathogen Neisseria meningitidis
, Nucleic Acids Research, Vol: 40, Pages: 2065-2075, ISSN: 1362-4962We 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.
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Journal articleNagorska K, Silhan J, Li Y, et al., 2012,
A network of enzymes involved in repair of oxidative DNA damage in Neisseria meningitidis
, MOLECULAR MICROBIOLOGY, Vol: 83, Pages: 1064-1079, ISSN: 0950-382X- Author Web Link
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- Citations: 20
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Journal articleBebeacua C, Förster A, McKeown C, et al., 2012,
Distinct conformations of the protein complex p97-Ufd1-Npl4 revealed by electron cryomicroscopy.
, Proc Natl Acad Sci U S A, Vol: 109, Pages: 1098-1103p97 is a key regulator of numerous cellular pathways and associates with ubiquitin-binding adaptors to remodel ubiquitin-modified substrate proteins. How adaptor binding to p97 is coordinated and how adaptors contribute to substrate remodeling is unclear. Here we present the 3D electron cryomicroscopy reconstructions of the major Ufd1-Npl4 adaptor in complex with p97. Our reconstructions show that p97-Ufd1-Npl4 is highly dynamic and that Ufd1-Npl4 assumes distinct positions relative to the p97 ring upon addition of nucleotide. Our results suggest a model for substrate remodeling by p97 and also explains how p97-Ufd1-Npl4 could form other complexes in a hierarchical model of p97-cofactor assembly.
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Journal articleKloppsteck P, Ewens CA, Foerster A, et al., 2012,
Regulation of p97 in the ubiquitin-proteasome system by the UBX protein-family
, BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, Vol: 1823, Pages: 125-129, ISSN: 0167-4889- Author Web Link
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- Citations: 55
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Journal articleOyarzún DA, Stan GB, 2012,
Synthetic gene circuits for metabolic control: design tradeoffs and constraints
, Journal of the Royal Society Interface, Vol: 10 -
Journal articleBatty EC, Jensen K, Freemont PS, 2012,
PML NUCLEAR BODIES AND OTHER TRIM-DEFINED SUBCELLULAR COMPARTMENTS
, TRIM/RBCC PROTEINS, Vol: 770, Pages: 39-58, ISSN: 0065-2598- Author Web Link
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- Citations: 7
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Journal articlePan W, Yuan Y, Goncalves J, et al., 2012,
Reconstruction of Arbitrary Biochemical Reaction Networks: A Compressive Sensing Approach
, 2012 IEEE 51ST ANNUAL CONFERENCE ON DECISION AND CONTROL (CDC), Pages: 2334-2339, ISSN: 0743-1546- Author Web Link
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- Citations: 21
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Journal articleLossi NS, Dajani R, Freemont P, et al., 2011,
Structure-function analysis of HsiF, a gp25-like component of the type VI secretion system, in <i>Pseudomonas aeruginosa</i>
, MICROBIOLOGY-SGM, Vol: 157, Pages: 3292-3305, ISSN: 1350-0872- Author Web Link
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- Citations: 40
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Journal articleZhang H-T, Chen MZQ, Stan G-B, 2011,
Fast Consensus Via Predictive Pinning Control
, IEEE TRANSACTIONS ON CIRCUITS AND SYSTEMS I-REGULAR PAPERS, Vol: 58, Pages: 2247-2258, ISSN: 1549-8328- Author Web Link
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- Citations: 99
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Journal articleDalchau N, Baek SJ, Briggs HM, et al., 2011,
The circadian oscillator gene <i>GIGANTEA</i> mediates a long-term response of the <i>Arabidopsis thaliana</i> circadian clock to sucrose
, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 108, Pages: 5104-5109, ISSN: 0027-8424- Author Web Link
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- Citations: 175
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Journal articlePeccoud J, Anderson JC, Chandran D, et al., 2011,
Essential information for synthetic DNA sequences
, NATURE BIOTECHNOLOGY, Vol: 29, Pages: 22-22, ISSN: 1087-0156- Author Web Link
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- Citations: 36
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Journal articleYuan Y, Stan G-B, Warnick S, et al., 2011,
Robust dynamical network structure reconstruction.
, Automatica, Vol: 47, Pages: 1230-1235 -
Journal articleMacDonald JT, Barnes C, Kitney RI, et al., 2011,
Computational design approaches and tools for synthetic biology
, INTEGRATIVE BIOLOGY, Vol: 3, Pages: 97-108, ISSN: 1757-9694- Author Web Link
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- Citations: 58
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Journal articleDalchau N, Hubbard KE, Robertson FC, et al., 2010,
Correct biological timing in <i>Arabidopsis</i> requires multiple light-signaling pathways
, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 107, Pages: 13171-13176, ISSN: 0027-8424- Author Web Link
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- Citations: 52
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Journal articleMhawej M-J, Brunet-Francois C, Fonteneau R, et al., 2009,
Apoptosis characterizes immunological failure of HIV infected patients
, CONTROL ENGINEERING PRACTICE, Vol: 17, Pages: 798-804, ISSN: 0967-0661- Author Web Link
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- Citations: 8
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Journal articleStan G-B, Belmudes F, Fonteneau R, et al., 2008,
Modelling the influence of activation-induced apoptosis of CD4<SUP>+</SUP> and CD8<SUP>+</SUP> T-cells on the immune system response of a HIV-infected patient
, IET SYSTEMS BIOLOGY, Vol: 2, Pages: 94-102, ISSN: 1751-8849- Author Web Link
- Open Access Link
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- Citations: 13
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Journal articleZhang H-T, Chen MZ, Stan G-B, et al., 2008,
Collective Behavior Coordination with Predictive Mechanisms
, IEEE CIRCUITS AND SYSTEMS MAGAZINE, Vol: 8, Pages: 67-85, ISSN: 1531-636X- Author Web Link
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- Citations: 68
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Journal articleZhang H-T, Chen MZ, Zhou T, et al., 2008,
Ultrafast consensus via predictive mechanisms
, EPL, Vol: 83, ISSN: 0295-5075- Author Web Link
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- Citations: 38
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Journal articleStan G-B, Sepulchre R, 2007,
Analysis of interconnected oscillators by dissipativity theory
, IEEE TRANSACTIONS ON AUTOMATIC CONTROL, Vol: 52, Pages: 256-270, ISSN: 0018-9286- Author Web Link
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- Citations: 205
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Journal articleSepulchre R, Stan GB, 2005,
Feedback mechanisms for global oscillations in Lure systems
, SYSTEMS & CONTROL LETTERS, Vol: 54, Pages: 809-818, ISSN: 0167-6911- Author Web Link
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- Citations: 18
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Work in the IC-CSynB is supported by a wide range of Research Councils, Learned Societies, Charities and more.