Group motility as a mechanism of self-defence in bacteria

项目概述：这个mrc资助的博士培训伙伴关系（DTP）将尖端的分子和分析科学与创新的数据分析计算方法结合在一起，使学生能够解决以假设为主导的生物医学研究问题。这是一个为期4年的课程，第一年包括一系列教学模块和两个基于实验室的研究项目，最终获得跨学科生物医学研究硕士学位。前两个学期包括一系列教学模块，让学生在多学科科学方面打下坚实的基础。学生还将参加一系列由分子、细胞和组织动力学、微生物学和感染、应用生物医学技术、人工智能和数据科学等领域的学术和行业专家主持的大师班。在第三学期和夏季学期，学生在他们选择的实验室进行两个为期11周的研究项目。项目：抗生素耐药性是细菌抵抗用于治疗它们的药物作用的能力。细菌获得耐药性的机制中，最不为人所知的是生理适应。这种适应的一个例子是，当细菌在一定的表面湿度和硬度条件下以群体而不是个体的形式移动时。这些菌群由鞭毛驱动的细菌组成，在有抗生素的情况下，鞭毛驱动的细菌在水面上快速扩张，入侵的区域比游动的细菌更大。了解蜂群运动是如何被触发的以及防御的物理机制将为我们提供停止蜂群形成和克服这些赋予抵抗的物理障碍的方法。蜂群开始于个体细胞水平上特定表型的表达，导致群体现象。因此，抗生素耐药性的增加被认为是由这两个尺度之间的相互作用引起的。因此，为了解决这个问题，我们将采取跨学科的方法，结合分子微生物学，细胞生物物理学和计算模拟。在计划的第一阶段，将会发展及完成一套双规模装置，将数据采集结合在菌落及单细胞水平。然后，在细菌暴露于不同环境条件（抗生素的种类和浓度，温度等）时，将在两个尺度上研究群体动态。同时，将开发一个数学模型，以找出由于群体运动而增加阻力的物理机制。最后，研究将集中在单细胞水平上对化学应激的反应，这将决定蜂群的抗生素暴露史。

Programme overview:This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice. Project:Antibiotic resistance is the ability of bacteria to resist the effects of medication used to treat them. One of the least understood mechanisms by which bacteria gain resistance is physical adaptation. An example of such adaptation is produced when bacteria move as swarms instead of as individuals under certain conditions of surface wetness and stiffness. These swarms consist in flagella-driven bacteria which expand over the surface at fast speed and invade larger regions than the swimming counterparts in the presence of antibiotics.Understanding how swarming motility is triggered and the physical mechanism of defense will provide us with methods to cease the swarming formation and to overcome these physical barriers which confer the resistance. Swarming starts with the expression of a specific phenotype at individual cell level which leads to a group phenomenon. The increase in resistance to antibiotic is hence supposed to be originated by this interplay between both scales. Thus, to address this problem, we will take an interdisciplinary approach combining molecular microbiology, cellular biophysics, and computational simulations.A dual-scale set up which combines data acquisition at both, colony and single-cell level scale will be developed and completed during the first stages of the project. Then, swarming dynamics will be studied in both scales when bacteria are exposed to different environmental conditions (sort and concentration of antibiotic, temperature, etc.). In parallel, a mathematical model will be developed to find out the physical mechanisms underlying the increase in resistance due to swarming motility. Finally, studies will focus on the response at chemical stress at single cell level which will determine swarmers' history of antibiotic exposure.