Scientists use new technology to analyze cell surface glycans

Every cell surface in our body is covered with dense sugar molecules, which play a key role in human development and disease. However, due to its complexity, it is still very difficult for scientists to understand the composition of these "glycans".

Researchers from the Emory University School of Medicine recently conducted research on glycans through gene chip microarray technology and a method they called "shotgun glycomics". Emory's team has developed a new chemical method to attach a fluorescent dye to purified glycans, and then separate individual glycans into multiple small dots and fix them on slides for testing. A detailed description of this method was published this week in the journal Nature Methods.

"These slides can separate and display all the glycans in the cells, so we can detect the substances that adhere to them. However, we still don't know the structure of these glycans at the moment." Senior author of the paper, Emory University Medical Dr. David Smith, director of the Center for Gastronomics and professor of biochemistry, said: "This is why we use the term 'shotgun' to describe our semi-random research approach."

After confirming the practicability of this technique, the research team used it to detect a specific molecule that can be recognized by the self-reactive antibodies present in the blood of most patients with Lyme disease. Lyme disease is a disease caused by the infection of Treponema pallidum after a bite of a tick. In severe cases, the immune system of the patient will have an autoimmune response to the bacteria.

"With this method we can analyze glycans, thus opening up a new way for the diagnosis of human autoimmune diseases, and it is possible to find new treatments that clear the body ’s autoreactive antibodies or inhibit their pathological attacks on cells. Method, "said Richard D. Cummings, the corresponding author and professor at Emory University School of Medicine.

Compared with protein or DNA, it is more difficult to completely analyze the structure of glycans, because glycans can form a variety of branched structures, and each of the chain links may be chemically different. Cells contain thousands of different glycans, which usually adhere to proteins or lipids. Scientists use this "shotgun" method to first find a glycan spot that specifically binds to proteins such as antibodies or toxins, and then focus on this glucan spot and determine its complete sequence. This method can help researchers select more important glycans from thousands of glycans on glass slides.

"The sugars present on glycoproteins or glycolipids play a decisive role in the function of these molecules," said Pamela Marino, a supervisor of the National Institute of General Medical Sciences' Glycobiology Research Fund under the National Institutes of Health, "understand the coding The information in these sugar molecules and the mechanisms by which they promote protein-protein interactions are crucial. This research was funded by high-risk research from the NIGMS EUREKA program and confirmed that the new 'shotgun' method is suitable for parsing glycan codes. It can be used to detect the role of glycans in infection and immunity. "

At present, the Emory research team has applied this method of "Sandball Glycomics" to red blood cells, tumor cells and brain-derived lipids. Cummings said: "This new technology can be used to find special sugar molecules displayed on cancer cells and has the potential to be used in the diagnosis or treatment of tumors."