University of Chicago Graduate is Winner of 2011 Nobel Prize in Medicine

Bruce Beutler, a 1981 graduate of the University of Chicago's medical school, was awarded the Nobel Prize in medicine for his discoveries on the immune system.  Dr. Beutler shares this year's prize in medicine with French scientist Jules Hoffmann and Canadian-born Ralph Steinman.

The Nobel Foundation explained that this year's Nobel Laureates in medicine have revolutionized our understanding of the immune system by discovering key principles for its activation. Scientists have long been searching for the gatekeepers of the immune response by which man and other animals defend themselves against attack by bacteria and other microorganisms. Bruce Beutler and Jules Hoffmann discovered receptor proteins that can recognize such microorganisms and activate innate immunity, the first step in the body's immune response. Ralph Steinman discovered the dendritic cells of the immune system and their unique capacity to activate and regulate adaptive immunity, the later stage of the immune response during which microorganisms are cleared from the body.

Dr. Beutler was searching for a receptor that could bind the bacterial product, lipopolysaccharide (LPS), which can cause septic shock, a life threatening condition that involves overstimulation of the immune system. In 1998, Beutler and his colleagues discovered that mice resistant to LPS had a mutation in a gene that was quite similar to the Toll gene of the fruit fly. This Toll-like receptor (TLR) turned out to be the elusive LPS receptor. When it binds LPS, signals are activated that cause inflammation and, when LPS doses are excessive, septic shock. These findings showed that mammals and fruit flies use similar molecules to activate innate immunity when encountering pathogenic microorganisms. The sensors of innate immunity had finally been discovered.

The discoveries of Hoffmann and Beutler triggered an explosion of research in innate immunity. Around a dozen different TLRs have now been identified in humans and mice. Each one of them recognizes certain types of molecules common in microorganisms. Individuals with certain mutations in these receptors carry an increased risk of infections while other genetic variants of TLR are associated with an increased risk for chronic inflammatory diseases.

For more on the 2011 Nobel Prize in Medicine, visit the Nobel Foundation's announcement web page, or the Chicago Sun-Times article on Dr. Beutler.