I have always been delighted by critters. When I was 13, my parents arranged for me to work as a veterinarian’s assistant at the Miami Zoo and later at a local dog and cat clinic. When I started college at the University of California at Davis, I wanted to be a vet, like my early mentors, but I dreaded anatomy demonstrations and memorizing names and locations of bones and muscles. By contrast, in biochemistry and molecular biology courses I could use logic to solve puzzles, and I was thrilled by the wondrous, miniature building blocks that made life possible: DNA, RNA, and proteins. I changed my major to biochemistry and my Grade Point Average soared.
In my junior year of college, my mom was diagnosed with colon cancer, and she died four months later. Her early death made my life’s work clear: to make meaningful contributions to medicine. With a sense of purpose and urgency, I joined Rick Troy’s research lab, and his postdoc, Eric Vimr, became my mentor. Eric introduced me to the power of bacteria as model systems to discover fundamental principles about life. I have studied bacteria ever since.
My graduate research in Saul Roseman’s lab at Johns Hopkins University focused on bacterial chemotaxis: how bacteria detect nutrients and swim to food sources. Near the end of my graduate studies, Mike Silverman came to speak at a local conference, and I was in the audience. Silverman introduced his topic by describing Nealson and Hastings’ 1970’s work showing how the symbiotic bacterium, Vibrio fischeri, emitted light as a collective. Nealson and Hastings had found that V fischeri produced, released, and responded to the accumulation of a small molecule signal which they called an “autoinducer”. Silverman told how Anatol Eberhard identified the signal molecule: it was a homoserine lactone.
Silverman went on to describe his own work, reported in a series of six, now landmark papers published between 1983–1987. Silverman, with graduate student Joanne Engebrecht and collaborator Ken Nealson, discovered, and cloned the genes underpinning the V fischeri cell-cell communication mechanism as well as the luciferase genes required for light production. Engebrecht and Silverman went on to sequence the genes, map their arrangement, characterize the protein functions involved, and show how the components interacted to yield density dependent bioluminescence. Silverman named the autoinducer synthase protein “LuxI”, and the autoinducer response protein “LuxR”. This was the first molecular description of a “quorum-sensing” circuit, a decade before the process received that name. Mesmerized by his seminar, I rushed to the podium immediately afterward and begged to become his postdoc.
I joined Silverman’s lab in 1990 to study Vibrio harveyi, a free-living bioluminescent bacterium. We showed that V harveyi had two autoinducers, two cognate receptors, and a protein linking the two systems. To our surprise, we found that the V harveyi quorum-sensing components did not resemble LuxI and LuxR of V fischeri. In 1993–94, we reported that a bacterium could have multiple quorum-sensing systems, and that distinctly different mechanisms had evolved to enable cell-cell communication. We did not know the identity of the second autoinducer, which we called “AI-2”, but we had hints that it was not a homoserine lactone.
I joined Princeton University’s Department of Molecular Biology in 1994. My lab identified LuxS, the AI-2 synthase. We showed that LuxS and AI-2 are broadly conserved in bacteria and that AI-2 is a universal signal that allows bacteria to communicate across species boundaries. We determined the biosynthetic pathway and structure of AI-2 and found that it was a five-carbon molecule containing boron, an element with surprisingly few roles in biology. We discovered quorum sensing in Vibrio cholerae and showed that the process controls virulence and biofilm formation. Later, we found that small non-coding RNAs lie at the heart of quorum-sensing circuits and they drive the internal quorum-sensing process. More recently, we developed quorum-sensing-modulating molecules that inhibit virulence in V cholerae and in Pseudomonas aeruginosa. We now study quorum sensing and its inhibition in scenarios mimicking those encountered by bacteria in the wild.
At Princeton, I have collaborated with exceptional students, postdocs, and faculty spanning physics, structure, chemistry, and engineering. I have been a Howard Hughes Medical Institute Investigator since 2005, and I am currently Chair of Princeton’s Department of Molecular Biology.
I am committed to teaching, service, and outreach aimed at informing non-scientists about the beauty and relevance of science. I have led efforts at Princeton and beyond to increase diversity within the scientific community. Some roles include: President of the American Society for Microbiology and Member of the Board of Governors of the American Association for the Advancement of Science. Nominated by President Obama in 1999, I serve on the National Science Board, which oversees the National Science Foundation and determines the nation’s research and educational priorities in science, math, and engineering.
In 2002, I married my long-time partner, Todd Reichart, who shares my love of nature and candid self-expression. I highly value his reliably unconventional and comical point of view. He is my biggest advocate, and I am his.
24 September 2015 Hong Kong
