The Shaw Prize in Life Science and Medicine is awarded in equal shares to
E Peter Greenberg Professor of Microbiology, University of Washington, USA and
Bonnie L Bassler Squibb Professor and Chair, Department of Molecular Biology, Princeton University and Investigator of the Howard Hughes Medical Institute, USA
for their discovery of quorum sensing, a process whereby bacteria communicate with each other and which offers innovative ways to interfere with bacterial pathogens or to modulate the microbiome for health applications.
Biographical Notes of Shaw Laureates in Life Science and Medicine 2015
The Shaw Prize in Life Science and Medicine 2015 is awarded to Bonnie L Bassler, Squibb Professor and Chair of the Department of Molecular Biology at Princeton University and an Investigator of the Howard Hughes Medical Institute, and E Peter Greenberg, Professor of Microbiology at the University of Washington, for their discovery of quorum sensing, a process whereby bacteria communicate with each other and which offers innovative ways to interfere with bacterial pathogens or to modulate the microbiome for health applications. Bacteria used to be regarded as lonely individual cells that act independently from their neighbours. Research in the past four decades has painted a completely different picture. Bacteria survive and thrive in communities in every imaginable habitat. In each community, bacteria communicate with each other and with other species to coordinate functions that are difficult or impossible to achieve by individual cells. These include uptake and processing of nutrients, coping with environmental stresses, and mounting attacks on host organisms. A ubiquitous bacterial communication strategy is quorum sensing, whereby bacterial cells sense and respond to changes in their local densities by the production and sensing of small, diffusible molecules. Bonnie L Bassler and E Peter Greenberg pioneered research in quorum sensing and elucidated the molecular mechanisms underlying quorum sensing as well as the implications of these mechanisms in controlling bacterial physiology in the context of infectious diseases. The phenomenon of quorum sensing has also been described in certain ants and honey bees. Recently, it has been identified in a mouse model concerning hair growth where the loss of one hair can stimulate hair growth in its neighbourhood. The recognition of quorum sensing and the elucidation of its underlying mechanisms is one of the most fascinating developments in microbiology. The notion of bacterial cells communicating within and between species has transformed the way we think of bacteria or interpret the implications of gene regulatory mechanisms. Each cell produces a small molecule that is transported into the environment by diffusion or secretion. The concentration of the molecule then reflects the density of the producing cells and can trigger gene expression response in neighbouring cells through a cognate receptor protein. This incredibly simple yet elegant mechanism enables bacteria to sense changes in their local densities or the physical environment, and to coordinate behaviour within a population or between the same or even different species. Understanding quorum sensing plays a critical role in controlling diverse bacterial functions, including generation of bioluminescence, formation of biofilms, and development of virulence. It points to innovative ways to interfere with bacterial pathogens or to modulate the microbiome for health applications. In addition to their roles in bacterial physiology, the molecular components underlying quorum sensing have been widely used in synthetic gene circuits to program dynamics of one or multiple bacterial populations and in controlling fermentation processes and producing products of interest. Both investigators contributed equally to the development of this important concept and the establishment of quorum sensing as a vibrant research field today. The Greenberg group provided definitive evidence that quorum sensing in Vibrio fischeri, a marine bacterium, is indeed mediated by diffusion of a chemical signal. His group mapped out the molecular components and mechanisms underlying this process and coined the term “quorum sensing” that crystalized the field. From the late 1990’s to the early 2000’s, Greenberg and colleagues elucidated the mechanisms of quorum sensing in Pseudomonas aeruginosa and its role in controlling the physiology of this pathogen. Recent work from Greenberg has integrated concepts from evolution and ecology to provide novel insights into quorum-sensing mediated cooperation. From the early 2000’s, the Bassler group mapped the molecular mechanisms underlying quorum sensing in Vibrio harveyi, another marine bacterium. Meanwhile, her laboratory elucidated mechanisms underlying quorum sensing in a different pathogen, Vibrio cholerae, and their implications in biofilm formation and virulence development. Bassler discovered that bacteria can communicate across species and defined the molecular mechanisms. This discovery adds another dimension to the concept of bacterial communication: the same bacterial population can use different chemicals to distinguish themselves from other populations. Bassler’s recent work has adopted a quantitative perspective in analyzing quorum-sensing mediated gene expression and the resulting evolutionary dynamics. The research by the two investigators has progressed in parallel. Both started with bioluminescence in marine bacteria and then moved on to pathogenic bacteria in humans. Both have demonstrated incredible focus in using well-defined model systems to establish the mechanistic basis of quorum sensing. Their studies have established the conceptual framework of our view of bacterial communication today and inspired fundamentally new ways to control bacterial dynamics for medical applications.