Microarray bioassays for functional glycome screening

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Complex sugars (glycans) are a highly diverse family of molecules with a broad range of functions in biological processes including cell recognition, adhesion, cell-cell communication and signalling. The study of the glycome - the entire set of glycans expressed by particular cells or tissues - is an emerging field which aims to understand how glycan functions underpin the complexity of human biology, and their involvement in disease processes. The selective interaction of proteins with glycans is the key to their biological functions. A number of new technologies have emerged to support such interaction studies, chief among these being microarray techniques ('glycoarrays'), which allow large numbers of individual glycans to be immobilised on surfaces for examination of their selective binding to protein partners. However, whilst allowing rapid large-scale screening, glycoarrays generate simple interaction data that do not directly reveal functional properties. In this project we propose to develop a novel glycoarray methodology in which live cell responses to large numbers of glycans arrayed on specially modified microscope slides are measured quantitatively. Responses such as cell growth or differentiation will be analysed by fluorescence measurements, using either antibodies or induced expression of fluorescent proteins by the cells themselves. This approach will provide a powerful and generic new tool for decoding the function of the glycome by allowing specific glycan structures to be matched to specific biological functions.