Self-organisation as the basis of bacterial chromosomal segregation

自组织是细菌染色体分离的基础

• 批准号: 439535737
• 负责人: Dr. Sean Murray
• 金额: --
• 依托单位: Abteilung System- und Synthetische Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/439535737?language=en
• 关键词: Self; organisation; basis; bacterial; chromosomal

Chromosome replication and segregation are critical processes for all cellular life. Replication of bacterial chromosomes initiates at a unique site called the origin, or ori, and proceeds bi-directionally down each chromosomal arm. In Escherichia coli and other bacteria, the ori is specifically positioned within the cell. In new-born cells, it is found at the cell middle, where replication is initiated. Duplicated ori are subsequently partitioned to opposite quarter positions where they remain for the remainder of the cell cycle. While these dynamics been very well studied, the underlying mechanisms are unknown.We have recently provided a novel explanation based on self-organisation of SMC (Structural Maintenance of Chromosomes) complexes, a ubiquitous family of proteins involved in chromosome organisation. MukBEF, the E. coli SMC forms dynamic clusters inside cells following the pattern of ori, described above. We have proposed that MukBEF is a self-organising and self-positioning system and presented a mathematical model based on stochastic pattern formation. Building on this model, we argue that self-organising MukBEF segregates and positions ori. We have shown that a specific interaction between MukBEF and ori leads to bidirectional attraction, resulting in accurate positioning and partitioning of ori. The latter is an emergent property of the system, arising from the fact that ori do not simply move up the MukBEF gradient but rather interact with it in a non-trivial way. The model is supported by both new and published experimental data.In this project, we aim to unravel the biological and physical mechanism organising the E. coli chromosome. Our first goal is a rigorous quantitative comparison of our spatial stochastic model with time-lapse fluorescence microscopy data. For this, we will develop an image analysis pipeline and a distributed computing and Bayesian inference framework. This will give us the ability to test biophysical hypotheses against the experimental data. We will use this approach to explore the precise nature of the interaction between MukBEF and ori. Lastly, we will examine the positioning and interaction with MukBEF of another important genomic region, the replication terminus, which also plays a role in determining the future division site.By developing the first quantitative model of chromosome segregation in E. coli, this work will provide fundamental biological and physical insights into one of the most fundamental aspects of the bacterial cell cycle. Furthermore, the Bayesian inference approach for comparing imaging data to a spatio-temporal stochastic model will be of interest for the study of other cell biological processes, while the model itself will appeal more broadly to the pattern formation community.

染色体复制和分离是所有细胞生命的关键过程。细菌染色体的复制起始于一个独特的位点，称为起源，或ori，并沿着每个染色体臂双向进行。在大肠杆菌和其他细菌中，ori特异性地定位在细胞内。在新生细胞中，它位于细胞中部，在那里开始复制。重复的ori随后被分配到相反的四分之一位置，在那里它们在细胞周期的剩余时间内保持不变。虽然这些动力学已经很好地研究，潜在的机制是unknow.We最近提供了一个新的解释的基础上自组织SMC（染色体结构维护）复合物，一个无处不在的家庭的蛋白质参与染色体组织。MukBEF、E.大肠杆菌SMC在细胞内按照上述ori模式形成动态簇。我们提出了MukBEF是一个自组织和自定位系统，并提出了一个基于随机模式形成的数学模型。在此模型的基础上，我们认为，自组织MukBEF隔离和位置ori。我们已经证明，MukBEF和ori之间的特定相互作用导致双向吸引，从而准确定位和划分ori。后者是系统的一种涌现性质，源于ori并不是简单地沿着MukBEF梯度向上移动，而是以一种非平凡的方式与之相互作用。该模型得到了新的和已发表的实验数据的支持。coli染色体。我们的第一个目标是我们的空间随机模型与延时荧光显微镜数据进行严格的定量比较。为此，我们将开发一个图像分析管道和一个分布式计算和贝叶斯推理框架。这将使我们有能力根据实验数据检验生物物理学假设。我们将使用这种方法来探索MukBEF和ori之间相互作用的确切性质。最后，我们将研究另一个重要的基因组区域，复制末端，这也起着决定未来的分裂位点的定位和与MukBEF的相互作用。大肠杆菌，这项工作将提供基本的生物学和物理见解的细菌细胞周期的最基本的方面之一。此外，贝叶斯推理方法比较成像数据的时空随机模型将感兴趣的其他细胞生物过程的研究，而模型本身将呼吁更广泛的模式形成社区。