Practical Tools For Innovation
O'Reilly Bioinformatics Technology
January 28-31, 2002 -- Tucson, AZ
Born Spartanburg, South Carolina, 1955. BA Computer Science and Mathematics, 1973, University of Southern Mississippi, where he did some work attempting to apply AI techniques to protein folding. Ph.D., Harvard University, 1982, Biochemistry and Molecular Biology, for studies with Mark Ptashne. As a graduate student, he showed that the E. coli lexA gene repressed genes involved in the response to radiation damage, cloned the gene, produced and purified its protein product using and in some cases extending the newly developed recombinant DNA methods, and studied binding of the repressor to its operators, showing that its differential binding affinity for these sites affected the timing of the response. As a postdoctoral fellow, also with Mark Ptashne, he tested a number of ideas about the mechanism of transcription regulation in yeast by using the prokaryotic LexA protein and in subsequent experiments creating chimeric proteins that carried LexA fused to activators native to yeast. These "domain swap" experiments established the modular nature of eukaryotic transcription regulators.
As a professor at Massachusetts General Hospital and Harvard Medical School (Genetics, starting 1985), Brent and coworkers used yeast transcription that depended on chimeric DNA bound proteins as a genetic probe for protein function in higher organisms. This work led to the development of working two-hybrid methods (1988-1993), to the ability to scale them up via interaction mating (1992-1994), and to the eventual development of protein interaction methods into broad but shallow way to learn more about biological function. In parallel (1993-2001), Brent and coworkers developed peptide aptamers as reverse "genetic" agents to study the function of proteins and allelic protein variants, and, more recently, as dominant forward "genetic" reagents to identify genes and pathway linkages in organisms, such as human cells, that are intractable to classical genetic analysis. Perhaps as important as the actual technologies is the coeval development by Brent and coworkers of ideology (e.g. doctrine) for using them. This work is described in about 80 research papers and reviews.
In parallel to his academic work, Brent is a longtime (since 1984) advisor to the biotech and pharma industries. He serves on the SAB of American Home Products (GI/WAR), chairs scientific advisory boards for several smaller companies, and does significant ad hoc consulting work in genomics and computational biology. He is one of the founders (1987-2001) of Current Protocols, including Current Protocols in Molecular Biology, a "how to clone it" manual, which is updated every three months and has about 10,000 subscribing labs, and he is founder and organizer (since 1994) of the "After The Genome" workshops. He is an inventor on 10 issued and several pending US Patents. Since the middle 1990s, he has exhorted and advised various bodies in the US and abroad on functional genomics and computational biology, including in particular the NIH, the Wellcome Trust, the NSF, DARPA, and other parts of the US Defense Department.
In 1998, Brent started, with Sydney Brenner, The Molecular Sciences Institute in Berkeley, California. TMSI (www.molsci.org) is a non-profit research institute. Its mission is to create a predictive biology by weaving together functional genomic and other experimental information and using that knowledge to develop predictive simulations of biological function. If successful, work at the Institute will increase biological understanding and may bring about new models for human therapy. It may also shed light on how living systems process information and contribute to the rise of a design based engineering of biological systems. In late 2000, Brent joined the faculty at UCSF as an adjunct professor and became Director of the Institute. In 2001, he was named CEO, President, and Chair of the Institute Board of Trustees.
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