“Shotgun” method exposes cells’ sugar coatings

Almost every type of cell in the human body is covered in sugar molecules called glycans, but scientists have found that analyzing and understanding these molecules have proved difficult because of their structural complexity.

A new method called shotgun glycomics could make it easier for scientists to understand the information encoded in the sugars and the sugars’ ability to facilitate interactions with other proteins. Adapting gene chip microarray technology, researchers at Emory University School of Medicine have developed a new chemical method for attaching a fluorescent dye to glycans purified from cells. The individual glycans are separated into tiny spots fixed onto glass slides, so scientists can determine what sticks to the glycans.

To demonstrate the technique’s utility, the team of researchers used the “shotgun” approach to identify a molecule recognized by self-reactive antibodies present in the blood of most patients with Lyme disease, which in severe cases has features of an autoimmune response.

“Being able to analyze glycans in this way may lead to new diagnostics for human autoimmune disorders and, perhaps, therapies to cleanse the body of self-reactive antibodies or inhibit their pathological attack on cells,” said Richard Cummings, chair of the biochemistry department and co-director of the medical school’s Glycomics Center.

In their work, which was published in Nature Methods, Vol. 8, pp. 85-90 (2011), the researchers explained the difficulty of completely dissecting a glycan’s structure. Because they form branched structures, not every link is chemically the same. In addition, scientists have estimated that cells can contain hundreds or thousands of different glycans, which can be attached to proteins or lipids. When using the shotgun approach, if scientists find that proteins from the body bind to one particular glycan spot, they can go back to that spot to determine its entire sequence.

The team has already applied shotgun glycomics to red blood cells, tumor cells and brain-derived lipids. Cummings is hopeful that the technique can be used to look for distinct sugar molecules displayed by cancer cells. Identifying cancer-specific glycans could then lead to diagnostic tools or therapies.

The study was funded by the National Institutes of Health’s National Institute of General Medical Sciences Eureka program for high-risk research.