Developmental imaging of bacterial biofilms with advanced microscopy, image processing and machine learning

生物膜是封闭在聚合物基质中的密集、空间复杂的细菌群落。据估计，超过65%的人类感染与生物膜相关，包括与囊性纤维化相关的铜绿假单胞菌肺部感染和大肠杆菌尿路感染。虽然生物膜的复杂结构是其显著的坚固性的原因，但我们对决定生物膜结构的发育和物理原理的理解目前非常有限。一个重要的原因是，目前很难以足够的分辨率观察生物膜的发育。为了解决这个问题，我们需要建立工具来观察一个微米大小的细菌是如何繁殖和分化成一个高度结构化的毫米级群落的。在攻读博士学位期间，您将为生物膜成像建立广泛使用的显微镜和图像处理工具。您将执行单细胞分辨率显微镜的生物膜，因为他们的生长和发展。然后，您将使用深度学习开发开源图像分析工具和软件，用于高分辨率3D细菌细胞分割和谱系追踪，以实现高鲁棒性和灵敏度。该项目的结果将是广泛有用的开源软件和开放科学协议，用于通过显微镜追踪结构化生物膜群落中的细菌发育。你的博士研究将做什么？您将从事高度跨学科的工作，包括定量生物成像（生物物理学和计算机科学）和微生物学。这将包括使用先进的显微镜和微流体技术在单细胞分辨率下对生物膜的发育进行成像，并开发新的图像处理方法，用于在空间和时间上对生长中的细菌进行三维单细胞谱系追踪。

Biofilms are dense, spatially complex communities of bacteria enclosed in a polymer matrix. Over 65% of all human infections are estimated to be biofilm-related, include cystic-fibrosis related Pseudomonas aeruginosa lung infections and Escherichia coli urinary tract infections. Although the complex structure of biofilms is responsible for their remarkable robustness, our understanding of the developmental and physical principles which determine biofilm structure is currently very limited. One important reason for this is that it is currently difficult to observe the development of a biofilm at sufficient resolution. To solve this, we need to build tools to observe how a micron sized bacterium multiplies and differentiates into a highly structured millimetre scale community. During this PhD you will establish widely useful microscopy and image processing tools for biofilm imaging. You will perform single cell resolution microscopy of biofilms as they grow and develop. You will then develop open source image analysis tools and software for high resolution 3D bacterial cell segmentation and lineage tracing using deep learning to achieve high robustness and sensitivity. The outcome of this project will be widely useful open source software & open science protocols for tracing bacterial development in structured biofilm communities via microscopy. What will you be doing for your PhD research? You will perform highly interdisciplinary work, working on both quantitative bioimaging (biophysics & computer science) and microbiology. This will include using advanced microscopy and microfluidics to image the development of biofilms at single cell resolution, and developing new image processing methods for three dimensional single cell lineage tracing of growing bacteria in space and time.