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Many proteins are particularly adept at functioning within their indigenous environments, but are often not suited for in vitro scientific and industrial applications. To bridge this gap, the Technology Development group uses in vitro compartmentalisation (also known as “artificial cell”) technologies to introduce desired properties into proteins with commercial potential. Such properties typically include improved expression levels, altered substrate specificity and increased thermostability. The Technology Development group is also developing novel variants of in vitro compartmentalisation that will enable high-throughput screening of protein-protein interactions.
Selected past publications by group members:
Directed evolution of p53 variants with altered DNA-binding specificities by in vitro compartmentalization.
Fen CX, Coomber DW, Lane DP, Ghadessy FJ.
J Mol Biol. 2007 Aug 31;371(5):1238-48. Epub 2007 Jun 9.
Compartmentalized self-replication: a novel method for the directed evolution of polymerases and other enzymes.
Ghadessy FJ, Holliger P.
Methods Mol Biol. 2007;352:237-48.
The XPF-ERCC1 endonuclease and homologous recombination contribute to the repair of minor groove DNA interstrand crosslinks in mammalian cells produced by the pyrrolo[2,1-c][1,4]benzodiazepine dimer SJG-136.
Clingen PH, De Silva IU, McHugh PJ, Ghadessy FJ, Tilby MJ, Thurston DE, Hartley JA.
Nucleic Acids Res. 2005 Jun 8;33(10):3283-91.
Generic expansion of the substrate spectrum of a DNA polymerase by directed evolution.
Ghadessy FJ, Ramsay N, Boudsocq F, Loakes D, Brown A, Iwai S, Vaisman A, Woodgate R, Holliger P.
Nat Biotechnol. 2004 Jun;22(6):755-9.
A novel emulsion mixture for in vitro compartmentalization of transcription and translation in the rabbit reticulocyte system.
Ghadessy FJ, Holliger P.
Protein Eng Des Sel. 2004 Mar;17(3):201-4.
Directed evolution of polymerase function by compartmentalized self-replication.
Ghadessy FJ, Ong JL, Holliger P.
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4552-7.
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