Natural products chemist to become Rockefeller's newest lab head

Following a yearlong search process involving an applicant pool of close to 700 candidates, Rockefeller University President Paul Nurse has announced that Sean Brady, a chemical biologist with a background in organic chemistry, microbiology and plant biology, will become assistant professor and head of laboratory at Rockefeller.

Brady, who will be the university’s first new head of laboratory in nearly two years and the first to be recruited under the university’s open recruitment process, intends to build his lab around the study of naturally occurring small molecules, such as those produced by soil bacteria and bacterial pathogens. It is a field rich in potential, with applications ranging from drug discovery to controlling the spread of harmful bacteria.

Brady’s multidisciplinary training allows for a fresh perspective in the burgeoning field of chemical biology, and his lab at Rockefeller will focus on two major areas within the discipline. The first, he says, is the discovery and study of new, drug-like small molecules from organisms that have not been studied before. “We want to develop technologies that will allow us to study molecules that have been inaccessible in the past,” says Brady, who is currently an instructor at Harvard University. His lab’s second focus will be the chemistry of bacterial pathogens. “Clearly, one of the ways microbes interact with the world is with small molecules. Trying to understand more about these small molecules should give us a better understanding of bacterial pathogens, and a better understanding of some infectious diseases.”

An education in molecular biology started early for Brady: During his high school years in Clinton, New York, he worked in his father’s plant molecular biology lab. He pursued the subject as an undergraduate at Pomona College in Claremont, California, where he received his degree in molecular biology in 1993. Brady chose Cornell for his Ph.D. research because it had a school dedicated to agriculture and life science. Once there, however, his interest in natural products chemistry led him to the laboratory of Jon Clardy, a trailblazer in the field of biological chemistry. He received his Ph.D. in organic chemistry in 2001, then made the transition to Harvard in 2004.

Studying soil bacteria has proven difficult for researchers because most of these microbes cannot be readily cultured in a laboratory setting. In fact, soil bacteria that have not yet been cultured outnumber those that have by at least three orders of magnitude. Uncultured bacteria, Brady says, are one of the largest remaining pools of untapped genetic diversity. “Gaining access to the small molecules produced by these organisms and the genes that encode the biosynthesis of these molecules should have implications for both basic science and drug discovery.”

Brady is finding novel ways to characterize the natural products from these microbes, extracting DNA from environmental samples (called environmental DNA, or eDNA) then cloning it in bacteria that can live in the lab. He plans to expand this approach by developing new eDNA cloning and screening systems and by studying uncultured bacteria found in soil samples collected throughout the world.

With the increase in antibiotic-resistant bacteria, the push to find strategies that control them has grown critical. Brady’s second focus, the chemistry of pathogenic bacteria, including their signaling systems and toxins, is loaded with downstream possibilities that could one day address this issue. “It’s trying to understand diseases better,” he says. “Bacteria produce signals, and toxins, that are clearly important for pathogenesis. If you can better understand these molecules, it may help control bacterial pathogens.”

Pathogenic bacteria have evolved elaborate signaling systems that are crucial to their ability to initiate and maintain infections. Brady plans to look at bacteria with known sequences to identify new gene clusters that code for novel signaling molecules and toxins. This line of research, he notes, could ultimately uncover ways to disrupt bacterial signaling networks, providing drug researchers with potential therapeutic targets.

Under the open recruitment process begun last fall, faculty candidates are evaluated on a university-wide scale. Rather than recruit within narrowly defined fields, scientists from across the biological and biomedical spectrum are considered simultaneously on an on-going basis. The university intends to hire as many as 10 mostly assistant professor-level candidates over the next several years.

“We are thrilled to welcome Sean to Rockefeller as the first new faculty member to be hired under our open recruitment process, and he is exactly the kind of highly innovative, cross-disciplinary scientist the process was created to identify,” says President Nurse. “Sean is doing extremely creative work with small molecules that has the potential to make enormous strides in one of the world’s most pressing public health areas, the treatment of infectious diseases. The faculty members and others who met with Sean during the recruitment process were unanimously enthusiastic about him, and we are fortunate to have convinced him to join the university.”

Brady plans to hit the ground running when he moves into his new lab, tentatively named the Laboratory of Genetically Encoded Small Molecules, at the beginning of September. “I’m very excited — no question about it. Rockefeller is a unique place, where a chemist can work alongside world-renowned biologists,” he says. “I was very impressed by the students, the postdocs, and the researchers. It’s a great community, and that kind of camaraderie is very important to me.”