Nick Riley

At a conference this spring, chemical biologist Nick Riley delivered a lightning talk in character as George Washington. Wearing a white powdered wig and accompanied by some members of his laboratory, he riffed on a popular Saturday Night Live sketch about US resistance to the metric system. But instead of expounding on inscrutable units of measure, Riley talked about the future of measuring glycans with mass spectrometry (MS).Campy? Perhaps a little. Riley, who has always been an extrovert, isn’t afraid to have a little fun. But he’s serious about pursuing better ways to study the biochemistry of sugars that decorate cell surfaces. He hopes that someday scientists could analyze these sugars en masse to infer the health of the cell. For example, how does a cell’s surface change as it accumulates abnormalities—and how does its new surface chemistry promote a slide toward cancer?Between three-quarters and nine-tenths of cell surface molecules sport glycan chains, scientists think. A glycoprotein might have many different sugar structures attached to many different amino acids within the protein, and these structures can be added, removed, or modified, rapidly adding up to thousands of unique chemical species. The abundance of different species is just one reason glycoproteins are hard to analyze. Another is that glycoproteins feature two incongruous chemistries—proteins and sugars. That molecular discordance “changes everything about the chemistry we want to study,” Riley says, including how a molecule behaves within a mass spectrometer.Biochemists often study proteins using MS because it allows them to determine a protein’s