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The problem with sugars
- Large-scale approaches for glycobiology

Glycobiology - the study of carbohydrates in biology - combines expertise in synthetic and analytical chemistry and carbohydrate biochemistry, as well as molecular and cellular biology, to unravel the structural complexity, chemistry, biosynthesis, and biological functions of sugar-bearing biomolecules. Over the past three decades, complex carbohydrates have become widely recognized as more than just an energy source [1]. Indeed, glycosylation has been established as a ubiquitous post-translational modification in higher organisms that enables one protein (or lipid) to function as many, and provides structural diversity that offers an explanation for the unexpectedly low number of genes in the human genome [2]. Complex sugars are major players in numerous biological processes, including developmental biology, the immune response and inflammatory disease, cell proliferation and apoptosis, the pathogenesis of infectious agents including prions, viruses, and bacteria, and a wide range of diseases ranging from rare congenital disorders to diabetes and cancer.

The incredible complexity of a cell's glycosylation machinery and its final products, a vast array of oligosaccharides (Figure 1), provides a research challenge in urgent need of high-throughput, large-scale technologies. Unfortunately, methods for studying and manipulating complex carbohydrates lag behind the tremendous advances made for nucleic acids and proteins [3]. Progress has been sluggish, in part because many biologists were slow to recognize the importance of sugars. But even when prescient researchers sought to uncover the role of glycosylation they were often frustrated by the difficulty of characterizing carbohydrates and the near impossibility of manipulating them with precision in living cells. In this article, we give a brief overview of the overriding factor hindering glycobiology - the incredible complexity of carbohydrates - before describing current technologies available for studying glycosylation and concluding with a guarded, but optimistic, prediction that glycobiology will catch up with other areas of biochemistry and molecular biology largely by virtue of promising large-scale technologies that are now on the horizon.

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