CARB POWER: Glycomics researches the multi-functional nature of carbohydrates

Seven years ago, ajit varki, professor of medicine at the University of California in San Diego (UCSD), discovered that human beings lack the gene to make a type of sugar molecule found in the brains of all other animals. They also found that our ancestors lost this gene more than two million years ago, after they started walking upright, but just before their brains started expanding. The amount of this sugar is low in the brains of all animals, which suggests that it is toxic in larger amounts. Was the loss of this gene partly responsible for the increase in brain size in human beings?

As scientists grapple with this question, they have another interesting fact to deal with. The sugar, known by the weighty name N-glycolneuraminic acid (Gc), is found in the human body as a contaminant through some foods. All human beings generate antibodies against this molecule, which means that the body treats it as an intruder, and a likely cause of disease. This discovery prompted Varki and his colleagues to set up a company called Gc-Free. Their plan is to develop kits to detect Gc antibodies and then develop drugs based on Gc. “Gc seems to be a good marker for cancer and other diseases,” says Varki. A marker indicates the presence of a disease, but more tests are required to determine precisely to what extent Gc is important.

Sugars are the newfound sweet spot for biologists and biomedical researchers, and their study constitutes an area of research called glycomics. The study of carbohydrates, as sugars are known in a technical sense, is one of the oldest branches of molecular biology, because carbohydrates were known much before proteins and genes (DNA) were discovered. But they were not studied well because genes and proteins appeared more glamorous and fundamental to life. For a long time, no one had the technology to rapidly characterise and find the sequence and structure of complex carbohydrates.

Now, this field is potentially one of the hottest areas of all science and technology, let alone of life sciences. Technology is maturing fast, and big money is beginning to be invested in private companies in this area. Genomics and proteomics have not yielded the magic bullets drug companies have hoped for. And it is now apparent that carbohydrates are involved in many critical biological processes, even in those involving proteins. Someone then coined the word glycomics, and an old area became new.

Many proteins need attached sugars to perform their function well. If these sugars are not present, or are present in the wrong form, it could result in a serious disease. On the other hand, cancer cells need the help of sugars to flourish. “Certain sugars in the blood could indicate the presence of specific types of cancer,” says Akhilesh Pandey, associate professor and cancer researcher at the Johns Hopkins University. His lab is working on such a sugar, called CA19-9, probably important in pancreatic cancer.

Sugars act like flags on cancer cells. Since these flags sometimes fall off into the bloodstream, we can use their presence to detect cancer. As a corollary, sugars can also be used to target anticancer drugs to cancer cells. We could design probes that can detect sugars in cancer cells, and then attach anti-cancer drugs on to these probes. Sugars also seem to play a role in the spread of cancer to other tissues, a process known as metastasis. It is the sugar on a protein that tells the cancer cells where to go, but this phenomenon is not well understood till now.