Bruce Alan Beutler M.D. (born December 29, 1957 in Chicago, Illinois) is an American immunologist and geneticist of Jewish descent. Together with Jules Hoffmann, he received one-half of the 2011 Nobel Prize in Physiology or Medicine, for "discoveries concerning the activation of innate immunity" (the other half went to Ralph Steinman for "his discovery of the dendritic cell and its role in adaptive immunity").
Beutler is currently Director of the Center for the Genetics of Host Defense at the University of Texas Southwestern Medical Center in Dallas, Texas and Professor and Chairman of the Department of Genetics at The Scripps Research Institute, in La Jolla, California. His father, Ernest Beutler, a hematologist and medical geneticist, was also a Professor and Department Chairman at Scripps.
Scientific discoveries[change | change source]
Beutler is best known for his pioneering molecular and genetic studies of inflammation and innate immunity. Interested in the mechanism by which lipopolysacchride (LPS) activates mammalian immune cells, Beutler identified the LPS receptor. Identification of the receptor hinged on the positional cloning (a method of gene identification) of the mammalian Lps locus, which had been known since the 1960s as a key gene for biological responses to LPS.
Beutler thus discovered the key sensors of microbial infection in mammals. He found that one of the mammalian toll-like receptors, TLR4, acts as the membrane-spanning component of the mammalian LPS receptor complex. The TLRs work in the perception of microbes. Ten are now known in humans. Each detects signature molecules produced early in an infection. These receptors also work in severe illness, including shock and systemic inflammation as it occurs in the course of an infection. They are also active in sterile inflammatory and autoimmune diseases such as systemic lupus erythematosus. The research on TLRs won him the Nobel Prize in 2011.
The positional cloning of Lps was completed in 1998. Beutler continued to analyse immunity in mammals. His work found numerous signalling molecules of the innate immune response, and helped to work out the biochemistry of innate immunity.
References[change | change source]
- Nobel Foundation (3 October 2011). "Nobel Prize in Physiology or Medicine 2011". Press release. http://www.nobelprize.org/nobel_prizes/medicine/laureates/2011/press.html.
- Genealogy of the Beutler family
- Sultzer B.M. 1968. Genetic control of leucocyte responses to endotoxin. Nature 219(5160):1253-4,
- Toll-like receptor: a protein which recognises bacteria, and triggers the immune response.
- Poltorak A. et al. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282(5396):2085-8
- Christensen S.R. et al. 2006. Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine (mouse) model of lupus. Immunity. 25(3):417-28
- Hoebe K. et al. 2003. Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 424(6950):743-8
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- Tabeta K. et al. 2006. The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9. Nature Immunol. 7(2):156-64