Sean Brady, PhD
Watch where you step, there is new chemistry everywhere
The Rockerfeller University
Laboratory of Genetically Encoded Small Molecules
One of the key revelations to arise from the large-scale sequencing of bacterial genomic DNA is that traditional approaches used for the discovery of natural products only provide functional access to a small fraction of the natural product biosynthetic gene clusters present in nature. The sequencing of DNA extracted directly from soil samples indicates that as yet uncultured soil microbes outnumber their cultured counterparts by at least two to three orders of magnitude. This uncultured majority no doubt produces secondary metabolites that could serve as molecular probes of biological processes and therapeutic agents. Uncultivated microorganisms are a very attractive source of potentially new natural products, but they are not amenable to the traditional approaches used to characterize natural products from microbes grown in pure culture. Although there appears to be no easy way to culture this collection of unstudied microorganisms, it is possible to isolate large fragments of microbial DNA directly from environmental samples and clone this DNA into model bacterial systems in the lab. We are using both functional and sequence-based screening strategies to access new natural product and new biosynthetic enzymes from large environmental DNA libraries.
Sean F. Brady graduated with a degree in molecular biology in 1993 from Pomona College in Claremont, California. He received his Ph.D. in organic chemistry from Cornell University in 2001. In 2002, he moved to Harvard Medical School as a fellow in the Institute of Chemistry and Cell Biology. He was named an instructor in the department of biological chemistry and molecular pharmacology at Harvard Medical School in 2004. In 2006 he moved to The Rockefeller University as an assistant professor. In 2009 Sean became a Howard Hughes Medical Institute Early Career Scientist. Sean’s research interests center on both the discovery and functional characterization of new genetically encoded small molecules. One area of particular interest is the development of methods to access new biologically active small molecules from uncultured bacteria.