Bruce Beutler is Professor and Chairman at the Department of Genetics, The Scripps Research Institute in La Jolla, California.
Prof Beutler has dedicated his research to answering one of the very key questions in immunology: How do we "know" when we have an infection? What are the receptors that alert us? For more than a century, and in fact, since microbes were recognized as the cause of infections, it has been clear that mammals are genetically programmed to recognize them. Moreover, it has long been an obvious corollary that certain molecules of microbial origin must trigger a host response, and that specialized receptors of the host must mediate recognition of these molecules. This, after all, is how biological systems operate. But what were these receptors?
Prof Beutler is probably best known for his pioneering molecular and genetic studies of inflammation and innate immunity. He was the first to isolate mouse tumour necrosis factor-alpha (TNF), and to demonstrate the role of this cytokine in inflammatory responses. He demonstrated that a soluble fusion protein consisting of the TNF receptor and the heavy chain of an immunoglobulin protected against endotoxin-induced shock. This work eventually led to the development of the drug Etanercept, which is now widely used for the treatment of rheumatoid arthritis, Crohn’s disease, psoriasis, and other forms of inflammation.
Due to his interest in the mechanism by which endotoxin activates mammalian immune cells, Prof Beutler subsequently identified Toll-like receptor-4 (TLR4) as the endotoxin receptor, based on the observation that this receptor was mutated in a mouse strain resistant to endotoxin-induced shock. Prof Beutler thus discovered one of the key sensors of microbial infection. The TLRs (of which ten are now known to exist in humans) are now widely known to function in the perception of microbes, each detecting signature molecules that herald infection.
The Beutler laboratory now systematically employs a forward genetic approach to identify genes that are essential for the mammalian innate immune response, and to determine their functions relative to one another. In this process, his team takes advantage of randomly created germline mutations that alter immune function. Prof Beutler's work disclosed numerous essential signalling molecules required for inflammatory immune responses, and helped to delineate the biochemistry of innate immunity. In the course of their work, Prof Beutler and his colleagues also identified genes required for other important biological processes, including the regulation of iron absorption, hearing, and embryonic development, since their disruption by random mutations created strikingly abnormal visible phenotypes.
Prof Beutler has been elected to numerous honorary academic societies. These include the United States National Academy of Sciences and the Institute of Medicine. Prof Beutler is also an Associate Member (foreign associate) of the European Molecular Biology Organization (EMBO), and a member of the Association of American Physicians and the American Society for Clinical Investigation.
Other notable honours include the Will Rogers Institute Annual Prize for Research (2009), the Albany Medical Center Prize (2009, shared with Charles Dinarello and Ralph Steinman), the Balzan Prize for Innate Immunity (2007, shared with Jules Hoffmann), the William B. Coley Award of the Cancer Research Institute, USA (2006, shared with Shizuo Akira), and the Robert Koch Prize of the Robert Koch Foundation, Germany (2004, shared with Jules Hoffmann and Shizuo Akira).
Prof Beutler has published more than 250 original papers and reviews, which together have received >41,500 citations. He is consequently ranked by Times Higher Education among the 20 Top Scientists in Immunology by total citations (1998-2008), and is listed by Thomson ISI as Highly Cited Researcher in Immunology.
The Jonathan Boulter Memorial Lecture 2011 is co-hosted by the BSI South Wales Immunology group and the Cardiff University School of Medicine Science Seminar series and is kindly sponsored by Miltenyi Biotec, Cambridge Bioscience and Stemcell Technologies.
Update from 3 October 2011: