Shotgun Glycomics

Shotgun Glycomics: New Microarray Technique Could Lead to Novel Diagnostics and Therapies

Almost all cells in the body are covered in sugar molecules, a "sticky" coating on the cell surface that allows it to bind with other cells, and also with pathogens such as viruses, bacteria, and parasites. The information encoded in these sugar molecules, called glycans, and how they interact with other proteins is valuable to decipher how they function. But sugar molecules have proven complex and difficult to study.

Richard Cummings, PhD
Richard Cummings, PhD

A new technique developed by Emory's Richard Cummings, PhD, Chair of the Biochemistry Department, and departmental colleagues David F. Smith, PhD and Xuezheng Song, PhD, uses gene chip microarray-type technology and fluorescent dyes to find out more about glycans. The tool involves releasing the sugars to get the free glycans, placing fluorescent tags on them, separating them, and placing them in spots on glass slides, with each spot being about 0.002 inches in diameter. At the outset, the researchers don't know what kind of glycan is in each spot, but they can probe them to figure out what sticks to them. They call this "shoot first, ask the details later" approach "shotgun glycomics."

"This in itself is important, to have a chemical library of the specific glycans," says Cummings, co-director of the Glycomics Center. "We print them on a glass slide (the "chip") and you can have 20,000 spots on one slide, easily. It's like having the Rosetta Stone, all it took was one word being translated to break the code." In this case, part of the translation is finding out which toxins or viruses bind to which glycan sequences. "Once we know a few of the structures, we can predict the others," he says. "And this technology focuses the power of mass spectrometry only on the glycans that are functionally important."

Schematic for Shotgun Glycomics

After "Shotgun glycomics: a microarray strategy for functional glycomics," was published in the journal Nature Methods, the technique received attention worldwide for its potential applications, including diagnostic screenings, determining flu strains, and autoimmune disease therapies. "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," Cummings says. "These assays are sensitive beyond imagination. Just 1/1000 of a drop of blood is enough to do all these tests."

"This is an outstanding platform technology that has applications in the biomarker, therapeutic target identification and the area of personalized medicine," says Justin Burns licensing associate in the Office of Technology Transfer.

The studies were funded by the NIH National Institute of General Medical Sciences EUREKA program for high-risk research and a Defense Advanced Research Projects Agency (DARPA) grant with Georgia Tech.

"In the future, we may be able to detect one molecule of cholera toxin," Cummings says. "I could see biochemical screening devices for airports, hospitals, homes. There are a lot of potential health and safety applications."

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