New technology will advance our understanding of role of complex sugar chains decorating the surface of cells in the body

Published on December 8, 2004 at 8:52 AM · No Comments

An international consortium of scientists lead by Dr. James Paulson of The Scripps Research Institute has created a technology that will advance our understanding of the role of complex sugar chains (glycans or carbohydrates) that decorate the surface of cells in the body.

The technology, known as a functional glycan microarray, is a glass slide onto which are printed hundreds of different glycan chains. The array offers scientists a cutting edge research tool allowing them to analyze the specificities of glycan binding proteins (GBP's), which function through their binding to such sugar chains.

The microarray will transform research in the burgeoning field of glycomics, which is devoted to the systematic identification and characterization of all the glycan structures produced by organisms. This field is a necessary component in understanding human health because of the importance of glycans as key players in all the body's functions. However, progress in elucidating this information and determining the biological functions of complex carbohydrates has lagged behind advances in the related fields of genomics (concerned with DNA, RNA and genes) and proteomics (concerned with proteins).

Many proteins involved in communication between cells recognize glycan structures on cell surfaces. The functional glycan microarray will speed research in glycomics, because it will allow scientists to determine to which carbohydrate structures these proteins bind.

"Any glycan-binding protein can be studied," says Professor James Paulson. "They all work."

The Scripps Research scientist Ola Blixt led this development together with Steve Head, the Director of Scripps Research DNA Microarray Core. Blixt, Head, and their colleagues developed the glycan array using a standard microarray printing technology analogous to an ink jet printer to arrange the sugars onto glass slides.

The arrays, which are described in an upcoming issue of the journal Proceedings of the National Academy of Sciences, were developed under the auspices of the Consortium for Functional Glycomics (CFG). In its present format the printed glycan array was established by the carbohydrate synthesis core which is directed by Blixt and coordinated by Paulson and Chi-Huey Wong, the Ernest W. Hahn Professor and Chair in Chemistry and an investigator in The Skaggs Institute for Chemical Biology at The Scripps Research Institute. The Consortium in which Paulson serves as Director and Principal Investigator, is funded by a $37 million "glue" grant awarded by the National Institute of General Medical Sciences, one of the National Institutes of Health and has brought together some 160 independently funded researchers at 110 different institutions around the world, including several in San Diego, with the goal of understanding how proteins in the body bind to carbohydrates and how these interactions mediate cell functions.

Carbohydrate structures are very much a part of the language of life. They are like the accents on spoken words—they change the meaning without changing the spelling. Some even call carbohydrates the third alphabet, behind DNA and proteins.

Glycosylation, the attachment of carbohydrate chains to proteins, is a crucial part of biology, and some scientists estimate that half of all proteins encoded by the human genome get sugars attached to them at some point after they are made. All cells, foreign and human, are covered with carbohydrates, and some viruses, like HIV and influenza, use sugars on the outside of human cells to gain entry into human cells.

Though they are not charged with storing genetic information like DNA or acting as enzymatic workhorses like proteins, carbohydrates nevertheless do carry information and are responsible for important biological functions, playing a central role in many types of intercellular communication events, protein folding, cell adhesion, and immune recognition.

One of the most important frontiers of basic research in biology today is to understand the human glycome—all of the types of carbohydrate structures in the human body and what they do. This is a profoundly difficult endeavor. The total number of carbohydrate structures in humans may be 10,000 to 20,000, although it is hard to fix a hard number to this, says Paulson. Nevertheless, he adds, "We think understanding the glycome is possible now. We didn't think that three years ago."

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