Berkeley, CA, USA--Carolyn Bertozzi, of UC Berkeley and the Lawrence Berkeley National Lab, has developed a series of techniques to manipulate glycans, sugars that occur throughout living things and are particularly abundant on the surfaces of cells. Her techniques provide, among other uses, a totally new way of visualizing vertebrate development.
Using developing zebrafish, Bertozzi and her colleagues tracked glycans moving and rearranging themselves. "We found some interesting and totally unexpected patterns as the sugars moved and clustered in certain areas." Bertozzi says, "It's like putting a new telescope up to the stars and seeing something new. And then you have to figure out what it is."
For instance, glycan patterns on cells in the mouth region (outlined in the grayscale image above, left) are shown (above, right) as they change beginning at 60 hours after fertilization (orange) and again an hour later (green).
Unlike proteins, glycans are not directly programmed by genes. They can't be labeled using genetic methods, in the way that a protein can be made to fluoresce by genetically combining its gene with that of a fluorescent protein. Instead, Bertozzi has devised ways to rig target glycans with reactive groups called "chemical reporters." Probes such as fluorescing molecules (fluorophores) are then sent in to react with the reporters.
Just over a decade ago, in what she called "an equal combination of cell biology and synthetic organic chemistry," she and her colleagues devised the key component of cell-surface engineering, the use of natural biological processes to plant artificial markers on the surfaces of living cells.
Bertozzi is director of the Molecular Foundry and professor of Chemistry and Molecular and Cell Biology, a Howard Hughes Medical Institute investigator, and a member of Berkeley Lab's Materials Sciences and Physical Biosciences Divisions. For more on her technique, see Imaging the Glycomes of Living Organisms at the Lawrence Berkeley National Laboratory site.