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UK GLYCOARRAYS CONSORTIUM

Funded by the RCUK Basic Technology Programme

  Research Councils UK logo
               
Research
               

Research Scheme

 

Basic schematic of the research: carbohydrates are either isolated from cells or synthesised by combinatorial chemistry and then immobilised on arrays. Endogenous or exogenous carbohydrate-binding proteins are added and binding is analysed using fluoresence spectroscopy, surface plasmon resonance and mass spectrometry

 

A new type of analytical chip that can observe the interactions between sugars and proteins is being developed by the Glycoarrays consortium. This consortium was formed by a collaboration between groups from the universities of Manchester, Oxford, UEA, Liverpool, Dundee and Imperial College London and its aim is to develop a set of novel technologies to generate ‘glycoarrays’ - assemblies of micro-arrays of carbohydrates that allow rapid analysis of their binding properties.

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.

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.

Array technology, however, is currently limited by the availability of all the possible carbohydrate structures and by the cost of synthesising those structures that are not available naturally. The latter is the greater challenge and involves three currently available routes: combinatorial carbohydrate chemistry, solid phase synthesis and production of synthetic enzymes. The combinatorial route in particular is expected to be the most useful in producing several thousand structures quickly for testing.

Once the samples have been successfully prepared, analysis will be carried out using fluorescence detection and mass spectrometry which are highly sensitive techniques and can be used to identify the compounds present in samples. Surface plasmon resonance (SPR) will be used to characterise binding properties such as specificity, kinetics and affinity.

As well as investigating the glycome itself, glycoarray technology will also be used to complement studies of the proteome, namely proteins that bind to carbohydrates. This will, in turn, be a useful tool in post-genomic studies, and subsequent studies of diseases of the immune system, and of wound healing, and tissue engineering. This research will also be of immense value to those involved in the development of new drugs known as glycotherapeutics.

 

 

 

Useful Links

UK Glycoscience Forum
CoEBio3
US Consortium for Functional Glycomics
RCUK

BBSRC

EPSRC
EUROCarbDB
 
 
 

University of Dundee logo

Imperial College London logo

The University of Liverpool logo

Prof. J. Turnbull

The University of Manchester logo

 

Prof. S. Flitsch

University of Oxford logo

Prof. B. Davis
Prof. T. Donohoe
Dr. A. Fairbanks
Dr. V. Gouverneur

University of East Anglia logo

Prof. R. Field
Prof. D. Russell

All content copyright The Glycoarrays Consortium 2006