Unravelling how bacteria use pili-based motility in biofilms

大多数细菌生活在称为生物膜的密集组合中。这些群落中的细胞使用一种叫做菌毛的微小抓钩将自己拉过表面。该项目旨在研究棒状细菌如何利用菌毛在表面上集体迁移。当这些细胞高密度地聚集在一起时，邻近细胞的运动倾向于彼此对齐，形成更大规模的流动模式，其外观类似于湍流。这个项目旨在了解不同基因型的细菌，它们以不同的速度和不同的长度移动，当它们混合在生物膜中时是如何竞争的。使用新的大规模细胞跟踪算法和基因工程细菌的组合，我们计划测量单个细胞如何改变它们在生物膜中的运动行为，以有效地作为一个集体在表面上扩散。为了支持我们的实验，我们将建立基于个体和连续体的模型，以解释拓扑缺陷（具有不同方向的细胞彼此相遇的点）如何在扩大的生物膜内相互作用。我们将使用最初开发的理论来研究液晶中的拓扑缺陷，作为我们建模工作的基础。我们的研究将分析铜绿假单胞菌的行为，铜绿假单胞菌是一种机会性病原体，也是易感患者感染的主要原因，包括烧伤患者和囊性纤维化（CF）携带者。最近，世界卫生组织将铜绿假单胞菌列为最需要研发新抗生素的三种细菌之一。学生进行的结合实验和建模程序将阐明细菌群落用于增殖和传播的基本物理和分子系统。因此，这项工作可能最终产生抗菌疗法的新靶点，这将使我们能够在临床环境中破坏生物膜感染的传播。这个高度跨学科的项目属于EPSRC的优先领域“生物和医疗保健的新物理科学”和“流体动力学”。

Most bacteria live in densely packed assemblages called biofilms. Cells in these communities use tiny grappling hooks called pili to pull themselves across surfaces. This project aims to study how rod-shaped bacteria collectively migrate across a surface using pili. When these cells are packed together at high density, the motility of neighbouring cells tends to align with one another, creating larger scale patterns of flow with an appearance similar to turbulence. This project aims to understand how different genotypes of bacteria, which move at different speeds and have different lengths, compete when they are mixed together within biofilms. Using a combination of new massively cell tracking algorithms and genetically engineered bacteria, we plan to measure how individual cells modify their movement behaviour in a biofilm to efficiently spread across a surface as a collective. To support our experiments, we will build both individual based and continuum models that will explain how topological defects (points where cells with different orientations meet each other) interact within an expanding biofilm. We will use theory originally developed to study topological defects in liquid crystals as the basis for our modelling efforts. Our study will analyse the behaviour of Pseudomonas aeruginosa, an opportunistic pathogen and major cause of infection in vulnerable patients, including burn victims and carriers of cystic fibrosis (CF). Recently, the World Health Organisation named P. aeruginosa as one of three bacterial species in greatest need of R&D for new antibiotic development. The combined experimental and modelling programme carried out by the student will elucidate the fundamental physics and molecular systems that bacterial communities use to proliferate and spread. This work, thus, may ultimately yield new targets for antimicrobial therapies that will allow us to disrupt the spread of biofilm infections in clinical settings. This highly interdisciplinary project falls both within EPSRC priority areas "New physical sciences for biology and healthcare" and "Fluid dynamics".