生命科學與醫學獎
2015

2015年度邵逸夫生命科學與醫學獎頒予邦妮・巴斯勒 (Bonnie L Bassler) 及彼德・格林伯格 (E Peter Greenberg)，以表彰他們闡釋群體感應的分子機制，一種細菌間相互溝通交流信息行為的調控機制；這項工作對干擾細菌的病原體或調控微生物群落在健康應用方面提供了新穎的方法。邦妮・巴斯勒是美國普林斯頓大學分子生物學系主任及Squibb講座教授，暨霍華德休斯醫學研究所研究員。彼德・格林伯格是美國華盛頓大學微生物學教授。

細菌是單細胞生物，一向被認為是單獨運作，不與鄰近細胞溝通。但過去40年的研究完全推翻了此觀念。細菌會在許多不同的棲息區內生存並茁壯成長。在每個區域中，細菌會與同類細菌以及其他物種溝通，進行功能上的協調；而這些功能對獨立的細胞而言，是很難甚至沒可能達到的。這包括攝入和處理營養素、應對環境壓力和增加對宿主的攻擊力。細菌相互溝通，並透過感應和生產細小的擴散性分子，去反映及回應其區域密度改變，這一種普遍存在的機制，就是群體感應。邦妮・巴斯勒和彼德・格林伯格闡明了群體感應的分子機制，在傳染病範疇裡，解釋了這些機制在控制細菌生理方面的含義。群體感應現象也曾在某些螞蟻和蜜蜂中被發現。近期它亦在小鼠模型中發現，當毛髮脫落時，它會刺激周圍的毛髮生長。

As implied in the term single-cell organisms, 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. Understanding quorum sensing is of fundamental significance for explaining how bacteria interact with each other or with their physical environment. It points to innovative ways to interfere with bacterial pathogens or to modulate the microbiome for health applications, and establishes a technological foundation for precisely controlling bacterial dynamics using artificial gene circuits.

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.