How biofilms protect themselves against bacteriophage infection and how they fail. (4573)

抗生素耐药性危机导致了人们对使用噬菌体这种细菌病毒来预防和清除感染的兴趣增加。但许多细菌生活在生物膜、细菌细胞的空间延伸结构和胞外聚合物(EPS)中。虽然乍一看，如此密集的细胞群特别容易被噬菌体降解，但生物膜中的生命提供了防止噬菌体捕食的保护。为了开发有针对性的噬菌体鸡尾酒来防止和清除生物膜，我们需要更好地了解生物膜是如何保护免受噬菌体侵袭的，以及这种保护是如何失败的：EPS是否太密集而不能被噬菌体分散？噬菌体有没有理想的吸附部位？一旦噬菌体感染在生物膜内开始，它是被控制的还是在局部传播？为了回答这些问题，你将进行模拟和实验的组合，这些实验来自微生物学和生物物理学。早期的实验，例如测量噬菌体T7渗透到大肠杆菌生物膜的深度，将允许你建立和参数建立一个进入生物膜并感染细胞的噬菌体模型。然后，该模型将预测修改生物膜时发生的变化，可以再次使用大肠杆菌和噬菌体T7，但也可以使用金黄色葡萄球菌和噬菌体K进行实验测试。这将使我们定量地了解生物膜是如何保护免受噬菌体攻击的，以及哪些杠杆可以被拉来克服这种保护。你将加入埃克塞特和巴斯的监督团队和研究小组，他们致力于将传统微生物学技术与最先进的成像以及模型建立和模拟相结合。首席主管Wolfram Möbius博士(Exeter)在T7噬菌体试验台上有理论背景和经验，与您一起专注于模型开发和模拟。第二位主管Maisem Laabe博士(巴斯)是金黄色葡萄球菌和成像方面的专家，将指导您的实验工作。巴斯、埃克塞特和纽卡斯尔的其他主管/合作者在整个项目中提供适用于电子显微镜、生物膜模拟、噬菌体鸡尾酒和多物种生物膜的额外投入。这个雄心勃勃的微生物学和生物物理学相结合的项目将为你提供在生命科学研究中被追捧的广泛技能，并有望增加我们对如何控制生物膜的理解。

The antibiotic resistance crisis leads to an increased interest in the use of bacteriophage, viruses of bacteria, to prevent and clear infections. But many bacteria live in biofilms, spatially extended structures of bacterial cells and extracellular polymeric substances (EPS). Although at first glance, such a dense population of cells should be particularly amenable to degradation by phages, life in the biofilm provides protection against bacteriophage predation.To develop targeted phage cocktails to prevent and clear biofilms, we need a better understanding of how biofilms are protected against phages and how this protection fails: Is the EPS too dense for phage to disperse? Is there an ideal number of adsorption sites for phage? Once a phage infection starts within a biofilm, is it contained or does it spread locally? To answer these questions you will perform a combination of simulations and experiments that draw from microbiology and biological physics.Early experiments, e.g., measuring how deeply phage T7 penetrates into a biofilm of E. coli, will allow you to build and parametrise a model of phage entering biofilms and infecting cells. The model then will make predictions about changes that occur when modifying the biofilm, which again can be tested experimentally again using E. coli and phage T7, but also S. aureus and phage K. Together, this will provide us with a quantitative understanding of how biofilms are protected against phages and which levers can be pulled to overcome this protection.You will join a supervisory team and research groups in Exeter and Bath which are dedicated to combining traditional microbiology techniques with state of the art imaging as well as model building and simulations. The lead supervisor, Dr. Wolfram Möbius (Exeter) has a theoretical background and experience at the bench with bacteriophage T7, focusing with you on model development and simulations. The second supervisor, Dr. Maisem Laabei (Bath), is an expert in S. aureus and imaging and will guide your experimental work.Additional supervisors/collaborators in Bath, Exeter, and Newcastle provide additional input on electron microscopy, biofilm simulations, phage cocktails and multispecies biofilms as applicable throughout the project. This ambitious project at the interface of microbiology and biophysics will provide you with a wide set of skills sought after in life science research and promises to increase our understanding of how to control biofilms.