Collaboration Leads to Immune System Cells Discovery

A collaborate effort between researchers at the Institute of Technology and the Academic Health Center has resulted in a new way to turn genes off in human T cells, a type of white blood cell that helps the immune system fight infections.

George Karypis, associate professor, Computer Science and Engineering, was part of the team, including researchers at Center for Infectious Diseases and Microbiology Translational Research (CIDMTR), Department of Microbiology, Department of Medicine, Department of Computer Science, and Division of Biostatistics, that used a novel approach to combine molecular biology and computational analysis to identify the mRNA sequence responsible for turning off T cells.

Researchers measured the rate of mRNA decay for each of the approximately 6,000 genes in human T cells. Karypis and his colleagues at the Minnesota Supercomputing Institute then analyzed the data by using complex computer programs to identify a sequence present in mRNA that was destroyed rapidly in the cell.

Paul Bohjanen, M.D., Ph.D., co-director of the CIDMTR and principal investigator of the study and his colleagues performed molecular biology experiments to confirm that this sequence targets mRNA for destruction and was responsible for turning off genes in activated T cells.

To date, understanding the mechanisms that turn off cells has not been very well understood. Turning off genes, through a process known as mRNA decay, is important for regulating the body's immune response after fighting infection. During an infection, T cells turn on and divide to help clear the infection from the body. After the infection is cleared, the cells need to turn off so the body can return to a stable condition. If the cells do not turn off, however, they can cause damage to the body and can potentially develop into cancer cells. The discovery offers hope of finding treatments for autoimmune diseases such as lupus and rheumatoid arthritis and for improving transplant safety. It also has implications in the fight against cancer.

"This discovery would not have been possible without the interdisciplinary collaboration between molecular biologists and computer scientists," Bohjanen said. The collaboration between Bohjanen and Karypis was facilitated by Irina Vlasova, M.D., Ph.D., research associate in Bohjanen's molecular biology laboratory, who received training in computational biology through a Minnesota Supercomputing Institute fellowship.

The research is published in the February 1 issue of Molecular Cell.