Roger Brent received a BA in Computer Science and Mathematics from the University of Southern Mississippi in 1973, where he applied AI techniques to protein folding. He earned his Ph.D. in Biochemistry and Molecular Biology from Harvard University in 1982 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 sometimes augmenting the new 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 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.
In 1985, Brent became a Professor at Massachusetts General Hospital and Harvard Medical School in the Department of Genetics. There, he and his coworkers used yeast transcription that depended on chimeric DNA-bound proteins as a genetic probe for protein function in higher organisms. This work contributed to the development of two-hybrid methods, to the ability to scale them up via interaction mating, and development of protein interaction methods and peptide aptamers to learn more about function via making and breaking interactions. Perhaps as important as the actual technologies was the coeval development of ideology (e.g. doctrine) for using protein interactions to make valid inferences about biological function.
In the late 1990s, Brent worked with Sydney Brenner to start the lab for the Molecular Sciences Institute in Berkeley, California. In 1998, Brent joined MSI as its Associate Director of Research. He became Director of Research in 2000, and President and CEO in 2001. At MSI, he and his coworkers began long term work to understand the quantitative function of a paradigmatic cell signaling system in budding yeast. This work revealed the existence of hitherto unsuspected persistent physiological states that affect signaling and gene expression. In 2009, he joined Fred Hutchinson Cancer Research Center as a Member in the Division of Basic Sciences and extended his research program to signaling systems in cells in animal tissues. This research has revealed additional physiological states. Consequences of cell-to-cell differences in these states include differences in complex outcomes for the organism including the impact of pre-existing mutations and lifespan.
Brent accepted appointments in the UCSF Department of Bioengineering and Therapeutic Sciences in 2001, the UW Genome Sciences Department in 2010, and the UW Bioengineering Department in 2014. In 2001, he was named a senior scholar of the Ellison Medical Foundation. In 2003, with Stanley Fields, he was awarded the Gabbaye Prize for his contributions to the development of two-hybrid methods. Brent was elected a fellow of the AAAS in 2011 for "contributions in the area of biochemistry, transcription, genomics and systems biology".
In parallel to his academic work, Brent helped found and works on (1987-2014) Current Protocols, a series of "how to clone it" and other lab manuals, accessed by more than three million scientists worldwide. He served on the SAB of American Home Products (Genetics Institute/Wyeth Ayerst Research), chaired SABs for several smaller companies, and does significant ad hoc consulting work. He is an inventor on 11 issued and several pending US Patents. He runs a pilot project, Center for Biological Futures (2011-2014) that works with social scientists and other scholars to better understand the impacts that developments in biology are having on human affairs. For some years he has carried out advisory work aimed at helping diminish the probability of biological attack and at taking advantage of other more positive impacts of developments in biology and related sciences.