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The glycome project
A sugar-coated proposal
By Bijal P. Trivedi

DNA, proteins, sugars, and fats are the major players that dominate the biology of the cell. The first two enjoy a prominent role in biology with vast genome and proteome projects to determine all of the genes and proteins produced by a living organism. Sugars and fats, however, are neglected. Now Japanese scientists have proposed a strategy to launch a "glycome project" to identify all of the sugars (glycans) as well as the sugar-protein and sugar-fat hybrid molecules that are produced by an individual organism.

The scientists, in a proposal published in a recent issue of Proteomics, suggest that the glycome project focus on Caenorhabditis elegans, a microscopic worm, whose entire genome is already sequenced.

The outer surface of the cell is a very dynamic environment. It is covered by a forest of sugar molecules, many of which are attached to proteins, fats or both. These molecules interface with the outside world and are critical for the communication between cells. Glycans also affect the stickiness of a cell, which is important for adhesion within organs. They are the first molecules to interact with various bacterial and viral intruders. Each cell type has a unique collection of sugars which changes as the cell develops.

"Glycans are nature's biologic modifiers," says Jamey Marth, a Howard Hughes Medical Institute investigator at the University of California San Diego."Glycans generally don't turn physiologic processes on and off, rather they modify the behavior of the cell by responding to external stimuli."

More than one percent of the genes in mammals encode enzymes that modify sugars or attach them to proteins and lipids which are destined to be posted on the cell's surface or among extracellular compartments, says Marth. Without these sugar attachments many proteins are unable to fold properly, and are directed to the wrong part of the cell. Defects in the assembly of sugar molecules or the sugar-protein hybrids are the basis for a growing list of human diseases.

There are many technical issues to be solved before high throughput methods can be applied to glycan analysis. The complex, branched structure of these sugars has made them difficult to analyze, but recent improvements in analytical methods offer hope that some processes may soon be automated. Learning how sugars modify proteins is critical for understanding how changes in the types of sugars on the cell surface alter susceptibility to disease.

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Hirabayashi, J. et al. Glycome project: Concept, strategy and preliminary application to Caenorhabditis elegans. Proteomics 1, 295-303 (March 7, 2001).

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