Insights of a Nobel Laureate: Weapons against infection
Dr. Beutler delivers President’s Lecture on innate immunity
By Deborah Wormser
How do insects thousands of miles away in Europe and rodents studied for years in an American laboratory intersect to unlock the secret of how our body’s immune system senses infection and fights back? Dr. Bruce Beutler shared insight into how this idea was born and evolved into his Nobel Prize-winning discovery on innate immunity at the President’s Lecture on Feb. 21.
Dr. Beutler, Director of the Center for the Genetics of Host Defense at UT Southwestern Medical Center, spoke on “Microbes, ’Merican Mice, and French Flies: How Your Resistome Recognizes and Fights Infection.”
The Nobel Laureate is famous for pioneering research done at UT Southwestern in 1998 that helped explain some age-old medical puzzles that his website summarizes as: “How do we ‘know’ when we have an infection? What are the receptors that alert us? How do we discriminate self from nonself, and why does the immune system sometimes attack our own cells and tissues?”
He explained how the unique atmosphere at UT Southwestern facilitated his identification of the family of Toll-like receptors that enable mammals to sense infection and to launch a powerful inflammatory response. Dr. Beutler also explained how his current endeavors could benefit researchers across campus and across disciplines.
Dr. Beutler’s talk included the story of how his research on mice converged with French scientist Dr. Jules Hoffmann’s studies in flies to reveal the fundamental framework by which creatures sense infection. Dr. Hoffmann and Dr. Beutler shared half of the 2011 Nobel Prize in Physiology or Medicine for their work on innate immunity.
Dr. Beutler also described the current research project he has under way to find every gene involved in how an organism recognizes and responds to potentially infectious agents like bacteria or viruses. Taken together, the genes that enable mammals to fight infection are known as the resistome.
At UT Southwestern, Dr. Beutler runs one of the largest mouse mutagenesis programs in the world. He and his group have tracked down more than 230 mutations that cause abnormalities in mice. Many of these mutations have important implications in infectious diseases or autoimmune conditions in which the body turns on itself, such as lupus and rheumatoid arthritis. Dr. Beutler’s team also has identified thousands of other genetic mutations that form the nucleus of a mutation archive that eventually will encompass all mouse genes.
Dr. Beutler recently incorporated the massive data-crunching capabilities of the Texas Advanced Computing Center in Austin to speed up his ambitious projects. The database he and his colleagues are generating will be a resource for investigators studying a range of genetic conditions including, perhaps, mutations that protect against cancer, he said.
Dr. Beutler considers genetics the single most successful branch of biology and the envy of researchers in nonmedical disciplines such as physics and chemistry that lack such a powerful tool. Oceans, stars, and mountains may be complex, but none of those inanimate objects contains a blueprint for its formation. Such a blueprint does exist in the genome of every living organism, he explained.
Reflecting on the importance of genetics, Dr. Beutler said: “Gregor Mendel discovered the particulate nature of heredity in the 1860s. The term ‘gene’ was coined in 1909 by a Danish botanist, Wilhelm Johannsen, and DNA was shown to be the stuff of which genes were made in 1944. But only in 1953 was the molecular structure of DNA deduced by James Watson, Francis Crick, and Maurice Wilkins. Their discovery initiated a great revolution in biology, which continues to unfold today.”
Dr. Beutler holds the Raymond and Ellen Willie Distinguished Chair in Cancer Research, in Honor of Laverne and Raymond Willie, Sr., and is a Regental Professor.