Exploitation of Glycoarrays -Translation to End-use
Lead Research Organisation:
University of Manchester
Department Name: Chemistry
Abstract
Carbohydrates are a large group of compounds consisting of sugars with diverse structures present both inside and on the surface of cells. They fulfil many different roles but it is the way they interact with proteins that determines their effectiveness in a variety of biological events. Each cell contains a wide variety of carbohydrates and the number of possible combinations and interactions with proteins and with other carbohydrates is enormous. These interactions are known to have a major effect on tumour growth, infectious diseases, inflammation, neurodegeneration, wound healing and tissue engineering. For example, it is now known that one of the factors influencing whether or not the influenza virus invades humans or birds is due to a very small difference in the structure of one of the sugar molecules on the surface of epithelial cells in the lungs and respiratory tract. Cancer is associated with changes of the sugar molecules attached to some proteins on the cell surface; tracking such changes may therefore be useful for diagnosing cancer and to provide a solution for specifically targeting drugs at cancerous cells. These examples indicate the complexity of the field of glycomics and the need for rapid progress. During the past four years, a consortium of scientists from the UK has developed technology to measure the interactions between carbohydrates and proteins that happen in cells, tissues or organisms (a field called 'glycomics'). This technology is centered around arrays which contain the natural carbohydrates that one might find in a biological system. The arrays are created by printing tiny dots of the carbohydrates of interest onto a support such as a glass slide, exposing them to carbohydrate binding proteins (CBPs) and finally observing and analysing the interactions. The present proposal aims to apply this technology to important biological problems. For example, we will investigate the binding of carbohydrates to protein components of the human immune system, to viruses and bacteria and to enzymes that are linked to disease states such as congenital muscular dystrophy. We will also investigate possible routes of application and commercialisation of the technology in healthcare.
Organisations
Publications

Pejchal R
(2011)
A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield
in Science

Neu U
(2013)
A structure-guided mutation in the major capsid protein retargets BK polyomavirus.
in PLoS pathogens

Liu Y
(2010)
Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus.
in Journal of virology

Otto DM
(2011)
An expression system for screening of proteins for glycan and protein interactions.
in Analytical biochemistry

Voglmeir J
(2011)
Biochemical correlation of activity of the a-dystroglycan-modifying glycosyltransferase POMGnT1 with mutations in muscle-eye-brain disease.
in The Biochemical journal

Klein F
(2012)
Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein.
in The Journal of experimental medicine



Feizi T
(2013)
Carbohydrate recognition in the immune system: contributions of neoglycolipid-based microarrays to carbohydrate ligand discovery.
in Annals of the New York Academy of Sciences

Gao C
(2014)
Carbohydrate sequence of the prostate cancer-associated antigen F77 assigned by a mucin O-glycome designer array.
in The Journal of biological chemistry

Nusse R
(2015)
Cell signalling: Disarming Wnt.
in Nature

Crusat M
(2013)
Changes in the hemagglutinin of H5N1 viruses during human infection--influence on receptor binding.
in Virology

Hiruma-Shimizu K
(2010)
Chemical synthesis, folding, and structural insights into O-fucosylated epidermal growth factor-like repeat 12 of mouse Notch-1 receptor.
in Journal of the American Chemical Society

Šardzík R
(2011)
Chemoenzymatic synthesis of sialooligosaccharides on arrays for studies of cell surface adhesion.
in Chemical communications (Cambridge, England)

Mouquet H
(2012)
Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies.
in Proceedings of the National Academy of Sciences of the United States of America

Suits MDL
(2014)
Conformational analysis of the Streptococcus pneumoniae hyaluronate lyase and characterization of its hyaluronan-specific carbohydrate-binding module.
in The Journal of biological chemistry

Khan ZM
(2014)
Crystallographic and glycan microarray analysis of human polyomavirus 9 VP1 identifies N-glycolyl neuraminic acid as a receptor candidate.
in Journal of virology

Nonaka M
(2014)
Determination of carbohydrate structure recognized by prostate-specific F77 monoclonal antibody through expression analysis of glycosyltransferase genes.
in The Journal of biological chemistry

Redelinghuys P
(2011)
Early murine T-lymphocyte activation is accompanied by a switch from N-Glycolyl- to N-acetyl-neuraminic acid and generation of ligands for siglec-E.
in The Journal of biological chemistry

Castangia R
(2016)
Fabrication and Application of Isotopically Labelled Gold Arrays for Multiplexed Peptide Analysis.
in Chembiochem : a European journal of chemical biology

Panagos C
(2014)
Fucosylated Chondroitin Sulfates from the Body Wall of the Sea Cucumber Holothuria forskali
in Journal of Biological Chemistry

Marchant J
(2012)
Galactose recognition by the apicomplexan parasite Toxoplasma gondii.
in The Journal of biological chemistry


Description | Gained further understanding using the technology of how carbohydrates interact with proteins in a variety of biological events. |
Exploitation Route | Use of the technology to study how carbohydrates interact with proteins. |
Sectors | Chemicals Healthcare Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
Description | This research resulted in further development of technology that has a wide range of applications in healthcare in particular diagnostics and drug discovery. |
First Year Of Impact | 2011 |
Sector | Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
Impact Types | Societal Economic |
Description | BBSRC Grouped |
Amount | £470,000 (GBP) |
Funding ID | BB/1004343/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start |
Description | BBSRC Grouped |
Amount | £470,000 (GBP) |
Funding ID | BB/1004343/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start |
Description | Commission of the European Communities |
Amount | £4,547,000 (GBP) |
Funding ID | 259869 |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start |
Description | Commission of the European Communities |
Amount | £4,547,000 (GBP) |
Funding ID | 259869 |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start |
Description | EPSRC |
Amount | £200,000 (GBP) |
Funding ID | EP/I016716/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start |
Description | Plant Bioscience Limited |
Amount | £28,000 (GBP) |
Organisation | Plant Bioscience Limited Technology |
Sector | Private |
Country | United Kingdom |
Start |
Description | Plant Bioscience Limited |
Amount | £28,000 (GBP) |
Organisation | Plant Bioscience Limited Technology |
Sector | Private |
Country | United Kingdom |
Start |
Description | University of East Anglia |
Amount | £10,000 (GBP) |
Organisation | University of East Anglia |
Sector | Academic/University |
Country | United Kingdom |
Start |
Description | Wellcome Trust, The |
Amount | £150,000 (GBP) |
Funding ID | WT093378MA |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start |