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 elucidating the molecular mechanism 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 neighbouring cells. 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 elucidated many of the molecular mechanisms underlying quorum sensing as well as the implications of the mechanism 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 mechanism are 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. While numerous quorum sensing systems have been discovered, they share the same fundamental architecture. Each cell produces a small molecule that is released into the environment by diffusion or excretion. The concentration of the molecule then reflects the density of the producing cells and can trigger gene expression in cells able to respond to this molecule, through a cognate receptor protein. This incredibly simple yet elegant mechanism enables bacteria to sense changes in their local densities or the physical confinement, and to coordinate behaviour within a population or between populations of the same or different species. It plays a critical role in controlling diverse functions, including generation of bioluminescence, formation of biofilms, and development of virulence. 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 in time and space.
Building on early work of Hastings, Nealson, Eberhard, Silverman, Engebrecht, Iglewski and others, both Greenberg and Bassler contributed 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 refined understanding of the details of the conserved molecular components and mechanism underlying this process and coined the term “quorum sensing” that crystalized the field. From the 1990’s, Greenberg and colleagues elucidated the mechanism of quorum sensing in Pseudomonas aeruginosa and its role in controlling the physiology and biofilm development of this pathogen. Recent work from Greenberghas integrated concepts from evolution and ecology to provide novel insights into quorum-sensing mediated cooperation.
Bassler began her venture in quorum sensing after she joined Silverman’s laboratory in 1990. From the mid 1990’s and building on earlier work by a number of groups on V fischeri, Bassler and her colleagues mapped details of the molecular mechanisms underlying quorum sensing in Vibrio harveyi, another marine bacterium. Meanwhile, her laboratory elucidated the mechanism underlying quorum sensing in a different pathogen, Vibrio cholerae, and their implications in biofilm formation and virulence development. Basslerelucidated the mechanism allowing bacteria to communicate across species and defined its molecular mechanism. Cross-species communication 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 pathogens. 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.
Life Science and Medicine Selection Committee
The Shaw Prize
22 July 2015 Hong Kong (Revised)