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

生物膜如何保护自身免受噬菌体感染以及它们如何失效。

• 批准号: 2859634
• 金额: --
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2859634
• 关键词: How; biofilms; protect; themselves; against

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.

抗生素耐药性危机导致对细菌，细菌病毒的使用，预防和清除感染的兴趣增加。但是许多细菌生活在生物膜中，细菌和细胞外聚合物物质（EPS）的空间扩展结构。 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 bacteriaiophage 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?是否有理想数量的用于噬菌体的添加吸附位点？一旦噬菌体感染开始在生物膜内，它是包含还是在本地扩散？为了回答这些问题，您将执行从微生物学和生物物理学中得出的模拟和实验的组合。例如，实验，例如测量噬菌体T7的深度渗透到大肠杆菌的生物膜中，您可以允许您构建和参数，并参数进入生物膜和感染细胞的模型。然后，该模型将对修改生物膜时发生的变化做出预测，可以再次使用大肠杆菌和噬菌体T7进行实验测试，还可以再次实验测试。微生物学技术具有最先进的成像以及模型构建和模拟。首席主管WolframMöbius（埃克塞特）在带有噬菌体T7的长凳上具有理论背景和经验，将您重点放在模型开发和模拟上。第二位主管Maisem Laabei（BATH）是S. Aureus and Imaging的专家，将指导您的实验性工作。Bath，Exeter和Newcastle的Additional主管/合作者提供了有关电子显微镜，生物生物生物生物模拟，Phage Cocktails和MultisPecies Bibecies Bibecies Biby Project As Special Project的其他投入。在微生物学和生物物理学的界面上，这个雄心勃勃的项目将为您提供生命科学研究后的广泛技能感，并有望增加我们对如何控制生物膜的理解。