Biological complexity: deciphering cell surface glycans (Introduction)

by David Turell @, Monday, May 03, 2021, 18:43 (10 days ago) @ David Turell

A whole new area being decoded:

"Gagneux pivoted to the study of the glycomolecules, or glycans, in that “rainforest canopy” that shrouds cells. Glycans are a spectacularly diverse group of complex sugars (polysaccharides). They can exist on their own — cellulose is a plant glycan made up of long chains of glucose — or they can be anchored to other biomolecules like proteins and lipids, whose chemical properties they modify. Their structure can be linear (as in cellulose), but they can also be very highly branched, adding to their variety and complexity.


"After analyzing a comprehensive data set of glycan structures and their known interactions, researchers at Harvard University and the Massachusetts Institute of Technology found a shared structural “language” that all organisms use when making glycans, like a municipal building code that ensures consistent, compatible architecture. The researchers have released a set of online tools that anyone can use to analyze glycan structures and functions.


"...glycans are still one of the greatest enigmas of the biological universe.” They’re “actually so prominent, they’re a major component of biomass on the planet.” In fact, glycans make up most of the organic matter by mass: Cellulose and chitin, the major building material of arthropod exoskeletons and fungal cell walls, are nature’s two most abundant organic polymers. And yet in contrast with the overabundance of glycans, “this whole field has been left behind,” Varki said.


"Bojar, who was a postdoctoral fellow at the Wyss Institute and MIT at the time, is the study’s first author. He and his colleagues observed 1,027 unique simple sugars (monosaccharides) and chemical bonds in the glycan sequences. They treated these as “glycoletters” — “the smallest units of an alphabet for a glycan language,” they wrote. They then began looking through the data set for patterns of “glycowords,” defined as sequences five glycoletters long (that is, three monosaccharides linked by two bonds).


"In theory, the glycoletters in the data set could have formed nearly 1.2 trillion different glycowords. Yet, surprisingly, the researchers’ results indicated that only 19,866 distinct glycowords were present across all the available sequences. Notwithstanding the immense complexity and diversity of glycans, and the differences in glycans that are characteristic of various species, the evidence suggested that all organisms follow very similar rules in assembling them and use essentially the same biomolecular language to define their structure.


"Antibody proteins latch onto specific antigen targets on pathogens. But it is the glycans linked to the proteins that determine how the antibodies interact with the rest of the body’s defenses and help to direct what kind of immune response follows. In the future, Bojar said, the tools might be able to suggest glycans that would improve the performance of antibodies, for example by limiting their side effects or more precisely calibrating their half-life in the body.

"Mahal noted that she is already using the tools to learn more about the specificity of the assays used to identify the glycans on cells. “These new computational technologies combined with high-throughput analysis will revolutionize our understanding of the glycome and its role in disease,” she said."

Comment: It seems every system in living biochemistry is organized in coded procedures. It is to early to fully understand this latest area of research, but it will blossom as DNA research has done. Not designed by chance.

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