Glowing zebrafish help researchers track role of sugars in the cell

Fluorescently tagged sugars finally allow study of role carbohydrates play on cell surface

Berkeley -- Using artificial sugar and some clever chemistry, University of California, Berkeley, researchers have made glow-in-the-dark fish whose internal light comes from the sugar coating on their cells.

This novel method of fluorescently tagging the sugar chains, or carbohydrates, that coat cells is a new tool for those studying development in the zebrafish, a laboratory organism popular because its transparent embryos allow easy observation of living cells as they develop over time.

"Most people think of carbohydrates as food, but the surface of any cell in our body is adorned with a ton of sugars as well as proteins that allow cells to communicate with other cells and invading pathogens," said UC Berkeley graduate student Jeremy M. Baskin. "People have had for many years the ability to image specific proteins, but not carbohydrates. We have developed for the first time methods for labeling and imaging carbohydrates inside an intact animal."

"An understanding of how, when and where cells dust themselves with sugar may shed light on how stem cells develop into tissues, as well as turn up markers of disease, such as cancer, or strategies for battling infectious organisms," said first author Scott T. Laughlin, who, like Baskin, is a graduate student in the Department of Chemistry.

One big advantage of the technique is that it is non-toxic and can be used to study living cells, Baskin said, whereas other methods of tagging cell-surface carbohydrates cannot be performed on living specimens.

Baskin and Laughlin, together with Carolyn Bertozzi, UC Berkeley professor of chemistry and of molecular and cell biology, and developmental geneticist Sharon L. Amacher, associate professor of molecular and cell biology, reported their results in the May 2 issue of the journal Science. Bertozzi also is director of the Molecular Foundry at Lawrence Berkeley National Laboratory, a Howard Hughes Medical Institute investigator, a faculty affiliate of the California Institute for Quantitative Biosciences (QB3) and the T.Z. and Irmgard Chu Distinguished Professor of Chemistry at UC Berkeley.

"We have genes in our body coding for proteins, but proteins get modified in lots of different ways, one of which is by addition of sugars that stick out on the cell surface and change the way the protein interacts with the environment," Amacher said. "One of the big mysteries is how the pattern of sugar modification changes during development, or in cancer cells versus non-cancer cells, for example. The exciting work Carolyn is now doing is finding ways that we can actually see the sugar labels on proteins."