News > BIO > Spring 2007 > Proteomics

Proteomics

Gone fishing: Discovery-based research foray lands a big catch

Gary Nelsestuen went on a scientific “fishing expedition” and caught a variant protein that predisposes people of American Indian and Mexican descent to diabetes.

It’s a big fish, in scientific terms, and a great story. It could help prevent diabetes in high-risk groups. It illustrates the value of proteomics research. And it proves that “fishing,” or discovery-based research, is worthwhile.

Nelsestuen embarked on his expedition a few years ago when he began using proteomics to screen blood samples for proteins related to diseases. He found one connected to obesity and diabetes in a sample from an American Indian donor.

The protein—apolipoprotein C1—transports cholesterol through the bloodstream.

All humans produce it, but this sample had a variation with characteristics indicating it could be the trigger for a hereditary disease, and diabetes ran in the donor’s family.

To further explore the connection, Michael Martinez, a graduate student in Nelsestuen’s laboratory, enlisted help from the American Indian Community Development Corporation in Minneapolis and St. Mary’s Health Clinics in St. Paul.

Blood proteins from more than 1,000 people of American Indian, European, African, Asian and Hispanic descent were evaluated. The variant was found in 36 of 228 American Indians in the study and 10 of 86 Mexicans, but not in any of the other groups.

Nelsestuen and colleagues published a description of the variant protein in fall 2006. In the February 2007 issue of the International Journal of Obesity, they reported that people with the protein tended to have a higher body mass index (an average of nine percent) and higher rates of diabetes. The diabetes rate was even higher when their parents were included in the pool.

The variant protein may allow carriers to store food as body fat and survive shortages, says Nelsestuen. This could have provided an advantage when food was scarce.

This project has been a departure for Nelsestuen, known for his discoveries of proteins involved in bleeding and coagulation disorders. The University licensed his blood-clotting proteins to companies that are developing them as drugs. Nelsestuen is recognized on the University’s Wall of Discovery for these achievements.

Supported by license income and his endowment from the Samuel Kirkwood Chair, Nelsestuen used mass spectrometry, a tool that reveals protein structure, to screen blood samples for unusual proteins. Called discovery-based research, this approach is 180 degrees from hypothesis-driven research. He is as proud of the source of funding and approach as he is of the discovery itself because they buck the traditional scientific establishment.

“This is dismissed as a fishing expedition by federal agencies, who usually fund only hypothesis-driven research,” Nelsestuen says. “But our finding shows the value of discovery research and of having unrestricted funds to pursue it.”

Nelsestuen’s next steps will be to expand the study to larger and more diverse groups of subjects.

—Peggy Rinard