Three microbiologists who helped pioneer the field of quorum sensing - how bacteria communicate with each other - are being honored with the 2023 Canada Gairdner International Award.
A virtual event originating from Toronto, Canada, will begin at 6 a.m. PDT on March 30 to name the 2023 Gairdner Momentum Award winners. The announcement will be followed by a Q&A with the recipients. The public can register to view the online event.
Each year, the Gairdner Foundation presents eight awards to individuals who have helped advance understanding of some of the most pressing biomedical and global health issues.
Greenberg, Sassler and Silverman have worked together and independently to explore a topic that at first received little attention from other scientists. In fact, some dismissed it as improbable. Only a few labs explored how bacteria interact with each other as a community. Now it is the subject of flourishing research that has attracted hundreds of researchers worldwide.
"When I started my own lab 40 years ago," Greenberg said, "microbiologists in general didn't think bacteria were social. They were just these little creatures that were really good at dividing and multiplying."
Greenberg, who grew up in the greater Puget Sound area and attended Western Washington University in the port city of Bellingham, initially headed toward a career in marine biology. As a postdoctoral scientist at Harvard University, he worked with a group studying bioluminescence in sea bacteria. Greenberg's mentor and his fellow lab researchers learned that the bacteria produced light only after they had reached the right population density. Greenberg and his colleagues determined that the tiny marine organisms were responding to a signal made by other bacteria of their own species.
Greenberg later turned his attention to a bacterial species that responded only to something it had made itself. He and collaborators showed how this signal gets in and out of a bacterial cell, and how a cell receptor activates the luminescence genes.
"The 1980s brought microbiologists around," Greenberg said. "Bacterial communication was true, but they were still not that interested. It was something some weird luminescent marine bacterium did."
Not until the 1990s did the biomedical importance of bacterial communications became clear. Microbiologists were becoming aware that a bacterium that could cause difficult-to-treat lung infections, Pseudomonas aeruginosa, had a gene sequence similar to that involved in light signaling in marine bacteria. Mutations in this gene made the Pseudomonas airway pathogen less virulent.
Greenberg at first resisted the call to examine these vicious bacteria.
"P. aeruginosa causes devastating infections in the lungs of people with the genetic disease cystic fibrosis," he said. "My daughter had cystic fibrosis and indeed her lungs were colonized with this beast. Could I study this bacterium in a dispassionate, scientific way?"
At first feeling that his hand was forced because he was an expert in bacterial signaling, Greenberg soon realized he could maintain the objectivity necessary to conduct this research. One of his graduate students, Jim Pearson, discovered that P. aeruginosa has two signaling systems. These were similar, but not identical, to the marine bacteria signals Greenberg had explored earlier.
"This was a big moment: learning that this human pathogen controls its virulence by sensing other members of species in its community," Greenberg recalled. "Now our colleagues believed and allowed that bacterial communication was important."
In 1994, Greenberg and two colleagues published a mini review describing the emerging field. They dubbed it "quorum sensing" because of bacteria's ability to determine when enough of them had gathered to get certain tasks done. He and co-authors set out the principles of cooperation and communication accomplished by bacteria through this signaling system.
Today, he said, through the achievements of many scientists, "we know that hundreds of bacteria use this type of system to control genes they use when together in a group."
Greenberg is a member of the National Academy of Sciences. He and his team have continued their work on P. aeruginosa. They have identified about 300 genes activated by the two quorum-sensing circuits in that bacterium. His team has also discovered ways that quorum-sensing systems are integrated into other gene-regulator systems in this bacteria.
An important offshoot of this research is that P. aeruginosa that carry quorum-sensing mutations form abnormal biofilms.
Biofilms are bacteria aggregating on a biological or artificial surface, such as a prosthetic implant inside a patient or on household items such as shower curtains. In a biofilm, bacteria can be hard to eradicate and impervious to antibiotics, Greenberg noted. A postdoctoral scientist in Greenberg's lab, Matt Parsek, developed both genetic and imaging approaches to analyze the growth and development of mutant bacteria biofilms. These tend to be more sensitive to antibiotic treatment than their non-mutant parents.
"This finding triggered a lot of activity in the biopharma arena towards targeting quorum sensing as a therapeutic approach," Greenberg noted.
He expressed the joy he takes from teaching and helping students achieve their goals. As a Gairdner laureate, he will travel to Canada to talk with college students about his field.
Looking to the future, Greenberg sees quorum sensing as ripe for the next generation of scientists seeking to make critical discoveries in biomedicine and environmental health.
"The biggest challenge is probably to develop a therapy that targets quorum sensing to tame human infections," he said. "I'm not addressing that challenge directly. That's something for others."
He sees the niche for his own research group as answering fundamental questions about microbial communities and how they operate.
He mentioned current work in his lab: "We now know that hundreds of different species of bacteria make these signals, but they're not all identical. Different bacteria make ones that are different from each other, so that an individual species can tell itself apart from other species. How did all that diversity arise? I'm presuming there was one original signaling system and somehow that spawned all these related ones. Can we in the laboratory make the Pseudomonas signaling system recognize and respond to a different signal?"
He thinks that might be possible.
"Our story is a great example of why basic, curiosity-driven research is so important."
Past UW Medcine recipients of Gairdner Awards:
- 2021 - Mary-Claire King, Medicine, Genome Sciences (International Award)
- 2018 - Christopher J.L. Murray, Global Health (Global Health Award)
- 2013 - King K. Holmes, Global Health (Global Health Award)
- 2010 - William A. Catterall, Pharmacology (International Award)
- 2003 - Linda B. Buck, Physiology and Biophysics (International Award)
- 2002 - Philip P. Green, Genome Sciences (International Award)
- 2002 - Maynard V. Olson, Medicine and Genome Sciences (International Award)
- 2002 - Robert Waterston, Genome Sciences (International Award)
- 2001 - Bertil Hille, Physiology and Biophysics (International Award)
- 1992 - Leland H. Hartwell, Genome Sciences (International Award)
- 1990 - E. Donnall Thomas, Medicine (International Award)
- 1978 - Edwin G. Krebs, Biochemistry and Pharmacology (International Award)
