What We Can Learn and Achieve through Glycan Research

Toshinori Sato (Professor, Department of Biosciences and Informatics)

Sugars are well known as sweeteners and energy sources, but there are sugars on the cell surface that play a different role. These are called "glycans" because they have a structure in which multiple sugars are linked together.

The types of glycans displayed on the cell surface differ depending on the cell type and are deeply involved in the properties of the cell. Glycans on the cell surface have various roles and are widely involved in the regulation of intercellular interactions and cell functions, such as ABO blood types and receptors for viruses and toxins. It is also known that cancer cells express different glycans than normal cells. Therefore, in recent years, they have been attracting attention in the fields of analyzing the causes of many diseases and developing therapeutic drugs.

In our laboratory, we are focusing on the recognition function of glycolipids present in the cell membrane and are studying the glycans involved in influenza virus infection and the interaction between beta-amyloid, the cause of Alzheimer's disease, and glycans.

To conduct new basic research, it is necessary to obtain glycans as research materials. The common methods for obtaining glycans are extraction from biological systems or production through organic or enzymatic synthesis. In contrast, we use animal cells as factories for glycan synthesis. In this method, when a "feed" called a "glycan primer" is given to cells, it is converted into long oligosaccharide chains by the action of intracellular glycosyltransferases. Using this principle, we have succeeded in producing many types of glycans. Using such glycans makes it possible to expand into new research. Furthermore, the glycan primer method can also be used to elucidate the glycan structures expressed in cells. We are focusing on technologies to perform such structural analysis in a high-throughput manner.

If the types of glycans expressed in cells and their functions are identified, it can lead to the development of new diagnostic methods and therapeutic drugs. Let me introduce one example. When the influenza virus infects, recognition of sialic acid-containing glycans on the host cell is involved (Fig. 1). If the binding between the virus and the glycan can be inhibited, influenza infection can be prevented. Our research group has found compounds that inhibit such glycan recognition by the influenza virus and is conducting research on them as new preventive and therapeutic drugs.

Here is another topic. Nucleic acids, such as genes, and proteins are attracting attention as new pharmaceuticals, but their instability in vivo and lack of specificity for target cells are problematic. Therefore, a "drug delivery system (DDS)" is needed to efficiently deliver them to target cells. In our laboratory, we use naturally derived polysaccharides to deliver nucleic acids and proteins into cells. We are particularly interested in a polysaccharide called chitosan, which is obtained from crab shells. By mixing nucleic acids and chitosan, genes can be efficiently delivered into cells (Fig. 2). By building on these results, we are developing a system that can perform gene therapy.

Fig. 2: Observation of plasmid DNA taken up by cells using a fluorescence microscope

This is a photograph taken with a fluorescence microscope, showing the uptake of a complex of plasmid DNA labeled with a fluorescent reagent and chitosan into cells. The white frame is the outline of the cell, and the green glowing part is the complex of plasmid DNA and chitosan taken up by the cell. At 5 hours, it can be seen that it is present within the cell nucleus. After this, the plasmid DNA is translated and proteins are synthesized.

As shown in these few examples, by investigating the functions of glycans, we can apply this knowledge to understanding the mechanisms of life and to research and development related to health.