Genomic analysis of regulatory networks for bacterial differentiation and multicellular behaviour

细菌是单细胞生物体，通常被视为相互独立地生活和活动。事实上，大多数细菌存在于大型群落中；这种生活方式的一个主要优势是极大地改善了对单个细胞的保护，使其免受环境压力的影响，如水分和养分的损失。群居是我们在大量细菌物种中观察到的为数不多的主要群落行为类型之一。在蜂拥而至的过程中，细菌会排成一大群，在一个表面上一起迁移。这是一种重要的医学现象：蜂拥而至使细菌能够迅速移动到宿主生物体中原本无法接触到的位置，并引发感染。例如，奇异变形杆菌是一种细菌，经常导致在医院获得的危及生命的感染。这些细菌蜂拥而至，并在人工医疗植入物上定植，进入患者的尿路，并上升到肾脏。除了在医学上的重要性外，蜂群是研究生物学中两个基本过程的极佳模型：(A)细胞如何变化，或“分化”为执行特定功能的不同类型的细胞；(B)单个细胞如何转变为协调其行为的多细胞群体。增加我们对这些过程的了解将有助于我们了解复杂的多细胞生物体是如何存在的。细胞通过感知与表面和彼此的接触而开始蜂拥而至。这引发了细胞的变形，细胞延长了20倍，形成了被称为鞭毛的长分子推进器，从细胞表面向外延伸。这些细长的细胞(数十亿)然后排列成大的细菌筏，并在同步的鞭毛旋转的推动下迁移离开。为了推动这一转变，一系列复杂的分子信号将初始刺激转化为激活或抑制蜂群所需的一组特定基因。我们知道其中许多基因的身份，比如那些负责鞭毛构造的基因。然而，也很明显，还有数百人参与其中，目前身份不明。此外，我们对传入的分子信号是如何传递来控制这些基因的活性只有一个基本的了解。我们将在我们和其他人以前在细菌遗传学、生物信息学和基因组学方面的工作的基础上解决这些问题。通过利用现有的方法和开发新的技术，我们将识别与细菌聚集有关的全部基因，并揭示控制它们的机制。在这样做的过程中，我们将揭示细胞分化和多细胞的新原理，并发现防止细菌移动到感染部位的方法。

Bacteria are single-cell organisms typically viewed as living and acting independently of each other. In fact, most bacteria exist in large communities; a major advantage of this lifestyle is the greatly improved protection of individual cells from environmental stresses such as loss of water and nutrients. Swarming is one of the few main types of community behaviour that we observe across a large number of bacterial species. During swarming, bacteria align themselves in a large group and migrate together over a surface. This is a medically important phenomenon: swarming enables bacteria to travel rapidly to locations in the host organism that are otherwise inaccessible and initiate infections. For example, Proteus mirabilis is a bacterial species that frequently causes life-threatening infections acquired in hospitals. These bacteria swarm over and colonise artificial medical implants to enter the patients' urinary tract and ascend to the kidneys. In addition to its importance in medicine, swarming is an excellent model for studying two fundamental processes in biology: (a) how cells change, or 'differentiate' into distinct cell types that perform specific functions; and (b) how single cells transform into multicellular populations that coordinate their behaviour. Increasing our knowledge of these processes will help us understand how complex, multicellular organisms exist. Cells initiate swarming by sensing contact with a surface and with each other. This triggers a metamorphosis in which cells lengthen 20-fold and build long molecular propellers called flagella that extend outward from the cell surface. These elongated cells (that number in the billions) then align to form large bacterial rafts and migrate away propelled by synchronised flagella rotation. To drive the transition, a complex cascade of molecular signals convert the initial stimuli to activate or repress a specific set of genes required for swarming. We know the identity of many of these genes, such as those responsible for flagella construction. However, it is also clear that several hundred more are involved which are currently unidentified. Additionally, we only have a basic understanding of how incoming molecular signals are transmitted to control the activity of these genes. We will address these problems by building on our and others' previous work in bacterial genetics, bioinformatics and genomics. By using existing approaches and developing new techniques, we will identify the full complement of genes involved in bacterial swarming and uncover the mechanisms controlling them. In doing so, we will reveal new principles underlying cellular differentiation and multicellularity, as well as discover ways to prevent bacterial movement to infection sites.