生命科学与医学奖
2015

2015年度邵逸夫生命科学与医学奖颁予邦妮・巴斯勒 (Bonnie L Bassler) 及彼德・格林伯格 (E Peter Greenberg)，以表彰他们阐释群体感应的分子机制，一种细菌间相互沟通交流信息行为的调控机制；这项工作对干扰细菌的病原体或调控微生物群落在健康应用方面提供了新颖的方法。邦妮・巴斯勒是美国普林斯顿大学分子生物学系主任及Squibb讲座教授，暨霍华德休斯医学研究所研究员。彼德・格林伯格是美国华盛顿大学微生物学教授。

细菌是单细胞生物，一向被认为是单独运作，不与邻近细胞沟通。但过去40年的研究完全推翻了此观念。细菌会在许多不同的栖息区内生存并茁壮成长。在每个区域中，细菌会与同类细菌以及其他物种沟通，进行功能上的协调；而这些功能对独立的细胞而言，是很难甚至没可能达到的。这包括摄入和处理营养素、应对环境压力和增加对宿主的攻击力。细菌相互沟通，并透过感应和生产细小的扩散性分子，去反映及回应其区域密度改变，这一种普遍存在的机制，就是群体感应。邦妮・巴斯勒和彼德・格林伯格阐明了群体感应的分子机制，在传染病范畴里，解释了这些机制在控制细菌生理方面的含义。群体感应现象也曾在某些蚂蚁和蜜蜂中被发现。近期它亦在小鼠模型中发现，当毛发脱落时，它会刺激周围的毛发生长。

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.