Although born in Chicago, Bassler spent her teenage years in Danville, California, and considers it her childhood home. Both her father, a businessman, and her mother, a stay-at-home mom, were the first members of their families to attend college. “They understood the value of education and how magical it is to have the opportunity to explore different career possibilities,” she says. Two after-school jobs — at a veterinarian’s office and at the local zoo — led Bassler to choose veterinarian sciences as her major when she entered the University of California at Davis in 1980. She soon realized, however, that it wasn’t a good fit for her. “I didn’t like the memorization, and I didn’t like the gore of dissection. It seemed a complete mismatch to me,” she recalls. What she did like were the required courses in biochemistry and molecular biology. “They were full of logic problems and puzzles. I just adored it,” she says. She switched her major to biochemistry.
In the summer before her senior year, Bassler’s mother died of colon cancer. To distract herself from her grief, Bassler threw herself into her studies. One day, she saw a bulletin board notice from a professor about two research possibilities for undergraduate students in his lab. One involved cancer, the other, bacteria. “I decided, in my naïve way, that I would find a cure for cancer,” she says. The professor assigned her to the bacteria project, however. “I was horrified,” Bassler says, “but of course now, I owe him a huge debt.” She quickly became fascinated with bacteria and has been working with those single-celled prokaryotic organisms ever since.
After graduating from UC Davis, Bassler crossed the country to attend graduate school at Johns Hopkins University, where she worked in the lab of biochemist Saul Roseman. For her thesis, she studied how the marine bacterium Vibrio furnissii adheres to and consumes the complex carbohydrates that form the shells of many marine organisms. “I noticed that the bacteria would sense the carbohydrates, swim to source, and then eat them,” she recalls. That observation led her to wonder about other types of sensory behaviors in bacteria.
As she was finishing up her PhD, she happened to attend a seminar by the geneticist Michael Silverman, who was then at the Agouron Institute in La Jolla, California. He talked about his research on Vibrio fischeri, a marine bacterium that becomes bioluminescent — glows in the dark — but only when sufficient numbers of other cells are present. It accomplishes this feat by a process known today as quorum sensing. The V. fischeri cells send out a chemical message, or autoinducer, that enables them to count their numbers, determine when they’ve reached a critical cell density, and then, as a collective, emit light. “I didn’t understand all of what he was saying because I wasn’t a geneticist at that time, but I thought what he was discussing was astonishing — that the bacteria acted in unison,” says Bassler. At this time — the late-1980s — bacteria were thought to be solitary, asocial organisms that acted strictly as individuals. Immediately after Silverman’s talk, Bassler ran up to the podium. “I said, ‘You have to let me come work for you,” she recalls. “Eventually, he relented.”
Silverman became a spectacular mentor. “He taught me genetics,” Bassler recalls. “I was his only post-doc at the time, and we worked together elbow-to-elbow.” In Silverman’s lab, Bassler discovered that another bioluminescent marine bacterium, Vibrio harveyi, produces and responds to two autoinducers to control its production of light. That was the first report of a bacterium using more than one autoinducer for cell-to-cell communication. She dubbed the second of these molecules autoinducer 2, or AI-2.
In 1994, Bassler joined the faculty at Princeton University, where she identified the gene — luxS — that is required for production of the V. harveyi AI-2 molecule. Bassler and her team then went on to make the seminal discovery that other bacterial species also have luxS, those bacteria make AI-2, and they use it to communicate across species. In other words, not only does each species of bacteria have its own private “language,” they also share a universal language — what Bassler calls “a bacterial Esperanto” — that enables them to converse with each other. Working with structural biologist Frederick Hughson, they identified the AI-2 structure. To her and Hughson’s amazement, that molecule was found to contain boron, a chemical that until that point had almost no known role in biology.
In subsequent research, Bassler’s lab found that the virulence of Vibrio cholerae, the bacterium that causes the disease cholera, is controlled by three autoinducer molecules. Bassler and her colleagues then went on to describe how V. cholerae uses quorum sensing to erect a biofilm, a kind of sticky, slimy bacterial “mat” that makes the bacteria resistant to harmful environmental compounds, including antibiotics. That work led them to identify the next new quorum-sensing autoinducer, DPO, that plays a role in shutting down biofilm formation and virulence in V. cholerae. Bassler has also made discoveries concerning quorum sensing in other globally-important bacterial pathogens, including Pseudomonas aeruginosa, which is key in lung infections and mortality in cystic fibrosis patients.
More recently, Bassler and her team made the remarkable discovery that bacteria-infecting viruses, known as phages, can eavesdrop on bacterial quorum-sensing conversations and use the information they garner to determine whether or not it is prudent to attack and kill their bacterial hosts. The phages do this by “surveilling” the environment for the DPO autoinducer, which enables the phages to determine if the bacterial head count in their vicinity is high enough for them to successfully find and infect a new host bacterium if they kill their present host. This finding is astonishing, for it reveals that chemical signaling occurs across radically different domains.
Bassler’s work on quorum sensing has revolutionized the field of microbiology. Not only has her research played a critical role in advancing our understanding of how the microbiome influences human health, her findings promise to lead to exciting new therapies for treating and preventing infectious diseases, including those that are increasingly becoming resistant to traditional antibiotics. “We understand bacteria in a profoundly different way than we did 25 years ago,” Bassler says. “But there’s so much more to learn. As the world gets more crowded and hotter, and as travel gets easier, the urgency to have new anti-bacterial agents becomes even more critical.”
Bassler continues to pursue her research at Princeton University, where she is chair of the Department of Molecular Biology. She is renowned for her mentoring of graduate students and postdoctoral fellows, as well as for her ability to communicate science to the public. She has also served in many scientific leadership positions, including as president of the American Society for Microbiology and as a member of the National Science Board. Through the years, Bassler has received numerous honors and awards for her work, including memberships in the National Academy of Sciences, the American Academy of Arts and Sciences, and the National Academy of Medicine. She is an investigator at the Howard Hughes Medical Institute, and, in 2002, she received a MacArthur Fellowship. Bassler is married to Todd Reichart, a science communicator at Princeton. In her spare time, she teaches aerobics and enjoys hiking and traveling. “As when I started at UC Davis, I still love animals,” she says, “so we travel a lot to see them in the wild.”