Genomic analysis of regulatory networks for bacterial differentiation and multicellular behaviour

细菌分化和多细胞行为调控网络的基因组分析

• 批准号: BB/E011489/1
• 负责人: Gillian Fraser
• 金额: $ 45.32万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE011489%2F1
• 关键词: Genomic; analysis; regulatory; networks; bacterial

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.

细菌是单细胞生物体，通常被认为是独立生活和相互作用的。事实上，大多数细菌都存在于大的群落中;这种生活方式的一个主要优点是大大改善了对单个细胞的保护，使其免受环境压力的影响，如水分和营养物质的损失。群集是我们在大量细菌物种中观察到的少数几种主要类型的群落行为之一。在群集过程中，细菌将自己排列成一个大群体，并在表面上一起迁移。这是一个医学上重要的现象：群集使细菌能够迅速移动到宿主生物体中的位置，否则无法到达并引发感染。例如，奇异变形杆菌是一种细菌物种，经常导致医院获得的危及生命的感染。这些细菌蜂拥而至，在人造医疗植入物上定居，进入患者的泌尿道，并上升到肾脏。除了在医学上的重要性之外，群集还是研究生物学中两个基本过程的极好模型：（a）细胞如何变化或“分化”成执行特定功能的不同细胞类型;（B）单细胞如何转化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是如何存在的。细胞通过感测与表面和彼此的接触来启动群集。这引发了一种变态，细胞延长了20倍，并建立了称为鞭毛的长分子螺旋桨，从细胞表面向外延伸。这些细长的细胞（数量以数十亿计）然后排列形成大的细菌筏，并在同步鞭毛旋转的推动下迁移。为了驱动这种转变，一系列复杂的分子信号将最初的刺激转化为激活或抑制集群所需的一组特定基因。我们知道许多这些基因的身份，如那些负责鞭毛建设。然而，同样清楚的是，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如何传递以控制这些基因的活性只有基本的了解。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。通过使用现有的方法和开发新技术，我们将确定参与细菌群集的全部基因，并揭示控制它们的机制。通过这样做，我们将揭示细胞分化和多细胞性的新原理，并发现防止细菌移动到感染部位的方法。

项目成果

Comparative genomics of cyclic-di-GMP signalling in bacteria: post-translational regulation and catalytic activity.

• DOI: 10.1093/nar/gkq382
• 发表时间: 2010-10
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Seshasayee AS;Fraser GM;Luscombe NM
• 通讯作者: Luscombe NM

Genomic analysis of DNA binding and gene regulation by homologous nucleoid-associated proteins IHF and HU in Escherichia coli K12.

• DOI: 10.1093/nar/gkr1236
• 发表时间: 2012-04
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Prieto AI;Kahramanoglou C;Ali RM;Fraser GM;Seshasayee AS;Luscombe NM
• 通讯作者: Luscombe NM

Direct and indirect effects of H-NS and Fis on global gene expression control in Escherichia coli.

• DOI: 10.1093/nar/gkq934
• 发表时间: 2011-03
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Kahramanoglou C;Seshasayee AS;Prieto AI;Ibberson D;Schmidt S;Zimmermann J;Benes V;Fraser GM;Luscombe NM
• 通讯作者: Luscombe NM