A group of glycomics researchers from about 15 organizations worldwide have come together to form the Human Disease Glycomics/Proteome Initiative, a HUPO-based effort led by Japanese organizers to promote the study of glycoproteins.
The group met for the first time last month in Osaka, Japan, at a meeting organized by Naoyuki Taniguchi, the chairman of the Department of Biochemistry at Osaka University. Organizations that had representatives at the meeting included the Seattle-based Institute for Systems Biology, Imperial College of the UK, the Burnham Institute of LaJolla, California, the University of Meunster in Germany, Taiwan’s Academica Sinica, and the Syndey, Australia-based Proteome Systems.
“We’ve found that proteomics researchers are accepting glycomics,” said Taniguchi, when asked how glycomics latched on to HUPO. “It’s impossible to ignore glycomics because over 50 percent of proteins are normally attached to sugars.”
During the two-day HGPI workshop meeting on Aug. 23-24, most scientists agreed that the first goal should be to standardize the process for glycoprotein analysis. To achieve this, HGPI organizers plan to purify a standard glycoprotein such as Immunoglobulin G or glycosyltransferase, then send an aliquot of the purified glycoprotein to member laboratories so they can analyze them using whichever techniques — such as MALDI or electrospray ionization —that they normally use. Representatives of the member HGPI laboratories will then share results of analysis with other HGPI groups to see if the results are comparable.
Once glycoprotein analysis techniques have been standardized, the goal of HGPI will be to screen for disease biomarkers. That initiative will probably start within the next two years, Taniguchi said.
Taniguchi was one of three glycomics researchers who gave talks on the last day of the sixth international proteomics meeting in Siena, Italy, which was held last week. Aside from pointing out that more than half of all proteins are glycosylated, Taniguchi said that at least half of all diagnostic tests use glycoproteins, and that more than 90 percent of the protein drugs in existence are glycoproteins.
As an example of how the glyco, or oligosaccharide, part of glycoproteins are important in diagnosing disease, Taniguchi talked about hepatoma, a liver cancer characterized by jaundice, liver failure, internal bleeding, and other complications.
Taniguchi explained that more than 70 percent of hepatoma patients produce a glycoprotein called AFP, or alpha-fetoprotein. It is not possible to tell by looking at AFP as a whole what complications of the disease will manifest in a patient. But if scientists analyze the sugar portion of AFP, they can tell if the patient will have certain symptoms, such as hepatitis or cirrhosis.
“The difference is in the sugar chain,” said Taniguchi. “You can use this for diagnosis.”
Other diseases that were presented by researchers as having good glycoprotein biomarkers included cystic fibrosis, other cancers, and Progeria, an early-onset ageing disease.
“If you start looking at sugars you see new biomarkers that we haven’t seen before,” said Nicolle Packer, a glycomics researcher at Sydney, Australia-based Proteome Systems.
Packer said she feels there hasn’t been a lot of acceptance of glycomics work so far, but a literature search performed by Packer showed that studies of glycoproteins have become increasingly popular within the last 30 years.
“Sugars have been found to be responsible for the correct folding of some proteins, for the increased activity of other proteins and for the control of the clearance of some protein drugs from the body,” said Packer. “Sugars themselves can give us biomarkers.”
Carlito Lebrilla, a glycomics researcher at the University of California, Davis, said oligosaccharides are not much more difficult to analyze than proteins. One advantage of oligos over proteins is that they are easier to quantify than proteins, Lebrilla said. Another advantage of glycosolation in terms of serving as a disease biomarker is that it may be more sensitive to disease and disease states than proteins.
“Glycosylation is the most common form of post-translational modification,” said Lebrilla. “Oligosaccharides have considerably more structural diversity than DNA or proteins.”
Catherine Fenselau, the president of USHUPO (see Proteomics Pioneer on page 7), said she is supportive of the Japanese-led glycomics initiative and may even be a little envious because the glycomics project is “more intellectual” than the American-led Human Plasma Proteome Project.
“I think I may like glycomics better,” Fenselau commented after introducing herself to Taniguchi at the Siena conference as the leader of USHUPO.
James Paulson, a professor at the Scripps Institute and the director of the NIH-funded Consortium of Functional Glycomics, said he sees collaboration between glycomics and proteomics researchers becoming increasingly common in the future.
“If you ask most proteomics researchers, they’re focused on the proteome, of course, and they try to ignore the sugar parts because it’s just too difficult to handle,” said Paulson, who was present at the Osaka meeting. “But in fact at least 50 to as high of 80 percent of proteins contain sugars as post-translational modification, so eventually the proteomics field will be forced to embrace the field of glycomics for that reason. I think most people are open to it, and I think they’d be quite happy to have another group of people working on the glycomics effort.”