New Vistas Lecture Series

Host: Paul Nurse, President, Rockefeller University

Speakers: Jennifer Zallen, Memorial Sloan Kettering Cancer Center; Sean Brady, Rockefeller University

The New Vistas lecture series has been created to celebrate the Academy's move to our new downtown home. In this series, the Academy has invited highly accomplished scientists to serve as hosts for an evening of "science at the frontiers." Each evening will feature talks by two up-and-coming scientists whose work has been identified by the host as exceptionally worthy of the spotlight.

Natural products from uncultured bacteria:Sean F. Brady

Many lines of evidence suggest that only a tiny minority of soil microbes is cultured using conventional approaches. Soil microbes that have not yet been cultured outnumber their cultured counterparts by two to three orders of magnitude, and 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 yet 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 large collection of unstudied microorganisms, it is possible to isolate large fragments of microbial DNA directly from environmental samples (environmental DNA, eDNA). Heterologous expression of eDNA in an easily cultured host could provide access to many of the natural products encoded by this previously inaccessible genetic material. I have worked on a general approach for accessing the natural products of uncultured microorganisms that omits culturing the producing organism. In this approach, which is designed to find small molecule antibiotics, eDNA is used to prepare cosmid libraries in Escherichia coli, and antibacterial active eDNA clones are found using a double antibiotic selection screen that was developed to identify and recover antibacterial active clones directly from the original library selection plates. New natural product antibiotics and their biosynthetic enzymes that were discovered using this approach will be discussed. A DNA-based approach for the discovery of natural products from large eDNA libraries will also be discussed.

Sean Brady graduated with a degree in molecular biology from Pomona College in 1993. He received his PhD in organic chemistry from Cornell University in 2001, where he studied under Jon Clardy. In 2002 he moved to Harvard Medical School as a Fellow in the Institute of Chemistry and Cell Biology and in 2004 he was named instructor in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. He started as an assistant professor at The Rockefeller University in 2006. Sean's research interests center on both the functional characterization and discovery of new genetically encoded small molecules from microbial sources, with a special interest in the natural products produced by uncultured bacteria and pathogenic bacteria.