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

抗生素耐药性危机导致人们对使用噬菌体、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，这样一个密集的细胞群体应该特别容易被噬菌体降解，但生物膜中的生命提供了对噬菌体捕食的保护。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攻击的，以及这种保护是如何失败的：EPS太密集以至于噬菌体无法分散吗？噬菌体的吸附位点是否有理想的数目？一旦噬菌体感染在生物膜内开始，它是被控制还是局部传播？为了回答这些问题，您将执行模拟和实验的组合，从微生物学和生物物理学中提取。早期的实验，例如，测量噬菌体T7穿透进入大肠杆菌生物膜的深度。大肠杆菌，将允许你建立和参数化噬菌体进入生物膜和感染细胞的模型。然后，该模型将预测改变生物膜时发生的变化，这可以再次使用E. coli和噬菌体T7，也可分离出S. aureus和噬菌体K.总之，这将为我们提供一个定量的了解生物膜是如何保护免受微生物，以及可以拉动哪些杠杆来克服这种保护。你将加入一个监督团队和研究小组在埃克塞特和巴斯，致力于结合传统的微生物学技术与最先进的成像以及模型构建和模拟。首席主管Wolfram Möbius博士（埃克塞特）具有理论背景和噬菌体T7实验室经验，专注于模型开发和模拟。第二位主管，博士Maisem Laabei（巴斯），是一个专家在S。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输入。在微生物学和生物物理学的接口这个雄心勃勃的项目将为您提供在生命科学研究中寻求广泛的技能，并承诺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.