UK GLYCOARRAYS CONSORTIUM
Funded by the EPSRC
Deadly virus reveals a potential weakness: A new study of the JC polyomavirus, a devastating pathogen that attacks brain cells in patients with compromised immune systems, has revealed how it binds to its targets, providing a basis for developing drugs to interrupt that process. Full article here
Y. Liu et al. Altered receptor specificity and cell tropism of D222G haemagglutinin mutants from fatal cases of pandemic A(H1N1) 2009 influenza, Journal of Virology, November 2010, Volume 84, Issue 22.
The consortium brings together scientists from the universities of Dundee, Liverpool, Manchester, Oxford, East Anglia and Imperial College London. The project officially began in May 2004 with an award of £3.5M from the Research Councils UK Basic Technology programme.
Carbohydrates interact with proteins in many biological processes such as fertilization, virus infections and even tumor growth. Therefore, structural and functional aspects concerning the interplay of the glycome (the complete set of carbohydrate structures produced by a particular cell or tissue) and the proteome (set of proteins) are of great interest in biology and medicine.
The aim of the present project is to develop carbohydrate arrays (glycoarrays) as innovative tools to map out the carbohydrate and protein partners in these highly specific interactions of the glycome. The project brings together a diverse set of novel technologies: from the generation of carbohydrate libraries (from natural sources, by chemical and enzymatic synthesis) and finding ways of linking the saccharides to a surface, to high throughput expression of carbohydrate binding proteins and the analysis of carbohydrate-protein binding by mass spectrometry, surface plasmon resonance and fluoresence measurements.
An understanding of the cell's glycome-protein interactions complements data from studies of the proteome and represents an essential facet of post-genome technology development that will underpin exploitation through development of novel glycotherapeutics in diverse applications such as cancer, infectious diseases, inflammation, neurodegeneration, wound healing and tissue engineering.
The RCUK Basic Technology webpage for this project is entiteled 'A sweet tool for glycome studies'
Glycoarrays Open Day
Some photos from the Glycoarrays Open Day held on Wednesday 18 October 2006 at the Manchester Interdisciplinary Biocentre.
van Kasteren, Sander I.; Kramer, Holger B.; Jensen, Henrik H.; Campbell, Sandra J.; Kirkpatrick, Joanna; Oldham, Neil J.; Anthony, Daniel C.; Davis, Benjamin G. (2007) Expanding the diversity of chemical protein modification allows post-translational mimicry. Nature 446(7139), 1105-1109
Avril, Tony; North, Simon J.; Haslam, Stuart M.; Willison, Hugh J.; Crocker, Paul R. (2006) Probing the cis interactions of the inhibitory receptor Siglec-7 with a 2,8-disialylated ligands on natural killer cells and other leukocytes using glycan-specific antibodies and by analysis of a 2,8-sialyltransferase gene expression. J. Leuk. Biol. 80(4) 787-796.
Duchesne, Laurence; Tissot, Berangere; Rudd, Timothy R.; Dell, Anne; Fernig, David G. (2006) N-glycosylation of fibroblast growth factor receptor 1 regulates ligand and heparan sulfate Co-receptor binding. J. Biol. Chem. 281(37) 27178-27189.
Powell, A, Zhi, Z, Turnbull, JE. (2006) “Heparan sulphate saccharide microarrays for high-throughput interrogation of protein binding interactions”. Methods in Molecular Biology (in press)
Liu Y, Chai W, Childs, RA, Feizi T. (2006) Neoglycolipid probes prepared via chemoselective oxime-ligation for microarray analysis of oligosaccharide -protein interactions . Methods Enzymol 415 (in press)
Campanero-Rhodes, MA, Childs, RA, Kiso, M, Komba, S, Le Narvor, C, Warren, J, Otto, D, Crocker, P, Feizi, T (2006) Carbohydrate microarrays reveal sulphation as a modulator of siglec binding. Biochem. Biohopys. Res. Commun. 344, 1141-1146
Zhi, Z, Powell A, Turnbull JE (2006) Fabrication of carbohydrate microarray on gold surface: direct attachment of non-derivatized oligosaccharides to hydrazide-derivatized self-assembled monolayer. Anal. Chem 78, 4786-4793
Crocker, P.R., Paulson, J.C., Varki, A. (2007) Siglecs and their role in the immune system. Nature Rev. Immunol. 7, 255-266
Morris, Howard R.; Chalabi, Sara; Panico, Maria; Sutton-Smith, Mark; Clark, Gary F.; Goldberg, David; Dell, Anne. (2007) Glycoproteomics: Past, present and future. Int. J. Mass Spec. 259(1-3) 16-31.
Bobbio, Carla; Gouverneur, Veronique. (2006) Catalytic asymmetric fluorinations. Org. & Biomol. Chem. 4(11) 2065-2075.
Haslam, Stuart M.; North, Simon J.; Dell, Anne (2006) Mass spectrometric analysis of N- and O-glycosylation of tissues and cells. Curr. Op.Struct. Biol. 16(5) 584-591.
Crocker, Paul R. (2005) Siglecs in innate immunity. Current Op. Pharmacol. 5(4), 431-437.
Flitsch, Sabine L. (2005) Synthetic chemistry: Glycosylation with a twist. Nature 437(7056) 201-202.
Turnbull, Jeremy E.; Field, Robert A. (2007) Emerging glycomics technologies. Nat. Chem. Biol. 3(2) 74-77