Sugar molecules coat every cell in our bodies and play critical roles in development and disease, yet the components of these "glycans" have been difficult for scientists to study, because of their complexity.
Researchers at Emory University School of Medicine have adapted gene chip microarray technology to the study of glycans, with an approach they call "shotgun glycomics." The Emory team has developed a new chemical method for attaching a fluorescent dye to glycans purified from cells. The individual glycans are separated into tiny spots fixed to glass slides.
The approach is described in an article published this week in the journal Nature Methods.
"These slides separate and display all the glycans in the cell, so that we can test what sticks to them," says senior author David Smith, PhD, professor of biochemistry and director of the Glycomics Center at Emory University School of Medicine. "However, the structures of the glycans are unknown. This is why we use the word 'shotgun' to describe our quasi-random approach of studying them."
The research team was led by Smith, first author Xuezheng Song, PhD, assistant professor of biochemistry, and Richard Cummings, PhD, chair of the Department of Biochemistry and co-director of the Glycomics Center.
As a demonstration of the technique's utility, the team used it to identify a molecule recognized by self-reactive antibodies present in the blood of most patients with Lyme disease. Lyme disease is caused by infection with Borrelia bacteria after a tick bite, but severe cases have features of an autoimmune response, triggered by the immune system's reaction to the bacteria.
"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.
Completely dissecting glycans' structur
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