January 2000

Sugar-coated Medicine

By Mark Dwortzan

DNA and proteins are the stars of biotech, but they aren't the only prime players in biology. Recent studies show that complex sugars called polysaccharides have a critical role in cell development and tumor formation. Like DNA, these sugars are composed of basic chemical building blocks whose sequence determines their biological functions. Until now, however, sugars have remained a bit player in the biotech revolution-partly because sequencing a single polysaccharide could take months.

A new technique developed by a pair of MIT researchers, Ram Sasisekharan and Ganesh Venkataraman, could change all that, allowing sugar sequences to be deciphered in days. By getting the job done much more efficiently and quickly, the MIT approach paves the way for researchers to clarify the exact roles complex sugars play throughout the body. The potential payoff: future drugs that target sugars linked to viral infections, cancerous tumors and other diseases. "The MIT group has taken this technique to a very high level of utility," says Merton Bernfield, a professor of cell biology at Harvard University.

Lodged between cells, polysaccharides known as glycosaminoglycans (GAGs) regulate cell-to-cell communication. These sugars are highly specialized; the arrangement of their building blocks dictates the message neighboring cells receive, and ultimately serves to differentiate organs. GAG sequences in the liver, for instance, differ substantially from those in the kidney; those in healthy tissues differ from those that are diseased. Biomedical researchers would like to be able to divide the body into unique, sugar-based "zip codes," says Venkataraman. "Once you know these zip codes, you can distinguish between normal and abnormal tissues."

The MIT researchers now aim to design a machine to automate the procedure. "We're at the tip of the iceberg in the polysaccharide field, where DNA and protein research was years ago," says Sasisekharan.