Protein-carbohydrate interactions, now recognized to be important mediators of cell communication, are the focus of the Consortium for Functional Glycomics (CFG), which has brought together seven Core facilities and a large international and multi-disciplinary group of Participating Investigators (PIs) with the common goal of elucidating paradigms by which glycan-binding proteins (GBPs) and their cognate carbohydrate ligands mediate cell communication. To accomplish its goals, the CFG has created unique tools needed to develop a global understanding of how identifiable patterns of glycan structures are created, how these patterns confer upon individual cells and glycoproteins signatures that are recognized by GBPs, and how these processes lead to responses impacting diverse biological systems from development to immunity. Unique tools created by the CFG include a glycan microarray for screening GBP specificity, a glyco-gene microarray for surveying expression of GBP and glycosyltransferase (GT) genes, a library of carbohydrate compounds for probing GBP function, and transgenic mouse strains with ablated GT or GBP genes. In addition, the CFG's Analytical Glycotechnology Core is preparing glycan profiles from selected human and murine tissues and purified cell populations as part of a focused glycomics effort to establish the natural glycan structures recognized by GBPs, and the Mouse Phenotype Core performs comprehensive phenotypic analyses of transgenic mouse strains of interest to the program. All resources are made available free of charge to the PIs and other investigators in the scientific community upon request. The roles of protein-carbohydrate interactions in aspects of innate and acquired immunity, including C-type lectins, siglecs and the CD1 T-cell receptor in dendritic cells, macrophages, natural killer cells and other leukocytes, are being explored, as are aspects of cell signaling mediated by galectins, siglecs and C-type lectins in various cell types. The scope of the program also includes microbial GBPs that mediate attachment to mammalian host cells. Construction of a specialized pathogen array will allow the identification of GBPs that bind to pathogen carbohydrate structures. Diverse data sets generated by the program are deposited into a relational database. Three specialty databases have also been created which provide an independent way of accessing CFG data, as well as seamlessly integrating a large amount of publicly-available information. Program data are highly integrated and readily accessed through user-friendly interfaces, presenting the field of glycobiology with a new way of looking at the overall complexity of glycans in the context of the functions mediated by GBPs.
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