Volume 2, Issue 13
Sweet Bioscience
UC Berkeley professor Carolyn Bertozzi keeps a close watch on carbohydrates, but it's not because she's on a trendy diet. In her chemistry laboratory, Bertozzi pays close attention to the carbohydrates that dot the surface of cells. These sugars decorating the cellular landscape are implicated in myriad biological processes, from intracellular communication to the growth of tumors. Bertozzi, a professor of chemistry and of biochemistry and molecular biology, and her graduate students have devised new chemical tools to uncover how the sugar structures change based on various factors. Someday, their research could aid doctors in diagnosing cancer and other diseases.
Carolyn Bertozzi, a researcher with the California Institute for Quantitative Biomedical Research (QB3), also studies tuberculosis to identify potential targets for drugs that would combat the disease. Bertozzi is also a professor of Molecular and Cellular Pharmacology at UC San Francisco. (LBNL photo)
"We work at the interface of chemistry and biology," says Bertozzi, a faculty scientist with Lawrence Berkeley National Laboratory (LBNL) and investigator with the Howard Hughes Medical Institute. "The chemical tools we develop allow us to probe these sugars to look at changes in their expression in different types of cells, both healthy and diseased."
A variety of sugars and sugar polymers (oligosaccharides and carbohydrates) are attached to the proteins and fats lodged in the cell wall. These sugars, collectively known as glycans, are involved in cell-cell interactions and infection by viruses, bacteria, and other diseases. As a result, their structure contains clues about the state of the cell itself. For example, glycans change during embryonic development and perhaps, Bertozzi says, even when stem cells differentiate.
While Bertozzi and her students have looked at the latter, they've made the most progress correlating certain glycan structures with cancer and other diseases. It's long been known that glycans harboring unnaturally high levels of sialic acid could indicate that the cell is cancerous. The trick though is observing the sugar structure and the glycosylation process, the addition of sugar molecules to proteins and other molecules. Only then, Bertozzi says, could physicians "look for signs in the sugar that something's wrong."
Last year, Bertozzi and her colleagues demonstrated a novel chemical reaction to "tag" the sugars on cells with tracer molecules called phosphines. The researchers used a live mouse "as a reaction vessel" without affecting the biology of the animal. By attaching a contrast agent or fluorescent dye to the phosphines, the surface sugars could then be seen using traditional medical imaging technology.
All cells decorate their surfaces with a variety of sugars and sugar polymers, called oligosaccharides. Carolyn Bertozzi attaches unnatural chemicals to simple sugars and feeds them to cells in order to get these chemicals onto the cell surface as part of the sugary landscape. (Bertozzi lab/UC Berkeley)
Bertozzi believes the highly-selective sugar tagging may result in fewer false-positives than current techniques to mark cells based on their metabolic activity. The researchers are currently developing tags that can be detected through positron emission spectroscopy (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI).
"Our hope is that we can use the reaction to target imaging probes to cells as a function of the cells' sugar patterns," Bertozzi says. "Visualizing glycosylation may be another way to look at a tumor."
As director of the Biological Nanostructures Facility of the Molecular Foundry at LBNL, Bertozzi is also exploring nanoscale materials with potential as biological probes. For example, the electrical properties of carbon nanotubes — tiny rolled-up crystalline sheets of carbon atoms — are highly sensitive to their environment. Someday, nanotubes might be introduced into the body to monitor the local conditions around a cell and whether it's responding to a particular analyte.
"When used in conjunction with existing imaging techniques, these tools may give us more reliable diagnostic capabilities," Bertozzi says. "It's always good to have options in your arsenal."