Glycoscience: a tea party no longer

Published in Protocols & Methods

Later this year or early next Richard Cummings plans to launch The Human Glycome Project. It will happen during a workshop that he is currently organizing and which is open to scientists from near and far. The workshop is slated to be held at the Radcliffe Institute for Advanced Study at Harvard University. Also in the works is a Harvard-based center for glycoscience that reaches out to potential collaborators at all Boston-area universities and academic medical centers.

Cummings, who hails from Alabama and who moved from Emory University School of Medicine to Harvard Medical School last fall, loves glycans, which are the ubiquitous carbohydrates made by all cells, and which can be linked to lipids or proteins. Both in humans and in a variety of animal species, the universe of glycolipids and glycoproteins is extraordinary, he says.

In Cummings’ box of plans is the development a human reference glycome so the growing research community committed to these macromolecules can explore the diversity of the human glycome and develop methods and standards with which to do so. He also envisions comparative glycomics, the comparison of human, porcine and bovine glycomics to tease out differences and similarities. “It wasn’t possible before, really,” he says. But dreaming big in glycoscience is now becoming possible.

Glycobiology has been hampered by complicated methods, which his and other labs have been addressing over the years. In his recent work, published the June issue of Nature Methods, the Cummings lab uses household bleach to release glycans from tissue and cells. He started this research at Emory School of Medicine and continued at his new lab at Harvard Medical School. He also directs the Center for Functional Glycomics, a virtual center that he already led at Emory and that is funded by the National Institutes of Health to explore protein-glycan interactions and to develop new tools and technologies to explore glycoconjugate functions.

When people now stop by the Cummings lab they can, for example, leave with four grams of carbohydrates in a 50ml tube full of white powder. “Those are all the carbohydrate structures in the pig lung,” he says. With this material on hand scientists can use nuclear magnetic resonance techniques for glycan analysis.

Cummings and his team want to enable more labs around the world to study glycoscience by shipping material to colleagues upon request.

Hear Rick Cummings talk about the offer here (14 seconds)

Glycans are difficult to synthesize but now it is possible to harvest them from natural sources such as eggs, meat or plants. “We can make them at such large scale now, we‘re going to just give them away,” he says. Once purified, glycans can be archived, printed on microarrays to explore glycan recognition by lectins, antibodies, bacteria or viruses, or sequenced with mass spectrometry, nuclear magnetic resonance techniques or other methods.

As researchers become aware of the role of carbohydrates in health and disease, the field of glycoscience is broadening, says Cummings. Glycans are being recognized as one of the four major classes of macromolecules, alongside nucleic acids, proteins and lipids.

In the 1970s and 1980s, this field was just getting its start and it was considered merely another part of biochemistry. When carbohydrate researchers got together at meetings, it was more like “tea parties” with 50 to 100 attendees, says Cummings. Glycoscience was far from the spotlight. The community began using the term glycobiology, which Raymond Dwek coined in 1985 and which resonated with researchers. And then, he says, “all of us kind of chose the term glycomics at some point to distinguish ourselves scientifically from proteomics and the other ‘omics.”

Hear Rick Cummings talk about the history of the field here (40 seconds)

Studying glycan function preceded the study of carbohydrate structure, says Cummings, a situation not unlike molecular biology. For example, work by the chemist Linus Pauling on sickle cell disease occurred before the responsible mutation had been identified and before it was possible to sequence DNA. “We really didn’t know the gene until years later,” says Cummings. The molecular biology arena exploded when it became possible to clone and to synthesize oligonucleotides. “We’re at that point now in glyco-science,” he says.

These days it’s increasingly difficult for scientists to overlook glycans, says Cummings. Access and collaboration are what is needed next to grow the field now that researchers are more than willing to, as he says, “dip their little toes in the glycoscience waters.” That being said, he does still hear disparaging comments about glycoscience, but he takes the remarks as a matter of pride. “So you can think of glycans as being like that little awkward kid on the playground who grew up to be a sizable individual whom no one bullies anymore.”

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