Group motility as a mechanism of self-defence in bacteria

课程概述：这个由MRC资助的博士培训伙伴关系(DTP)将尖端分子和分析科学与数据分析中的创新计算方法结合在一起，使学生能够解决假设引导的生物医学研究问题。这是一个为期4年的课程，第一年包括一系列的教学模块和两个基于实验室的研究项目，这些项目导致了跨学科生物医学研究的硕士学位。前两个学期包括精选的教学模块，使学生能够在多学科的科学中获得坚实的基础。学生们还参加了由学术和行业专家主持的一系列大师课程，这些专家涉及分子、细胞和组织动力学、微生物学和传染病、应用生物医学技术以及人工智能和数据科学等领域。在第三学期和暑期，学生们在他们选择的实验室里进行两个为期十一周的研究项目。项目：抗生素耐药性是细菌抵抗治疗药物效果的能力。细菌获得耐药性的最不为人所知的机制之一是身体适应。这种适应的一个例子是，在某些表面潮湿和僵硬的条件下，细菌作为群体而不是作为个体移动时就会产生这种适应。这些细菌群存在于鞭毛驱动的细菌中，它们在表面快速扩张，并比在抗生素存在的情况下入侵的游泳细菌侵入更大的区域。了解集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方法来阻止集群的形成，并克服这些产生抗性的物理障碍。群体现象始于特定表型在个体细胞水平的表达，从而导致群体现象。因此，抗生素耐药性的增加被认为是由这两种规模之间的相互作用造成的。因此，为了解决这个问题，我们将采取结合分子微生物学、细胞生物物理学和计算模拟的跨学科方法。在项目的第一阶段，将开发和完成一个结合了菌落和单细胞水平的数据采集的双尺度设置。然后，当细菌暴露在不同的环境条件(抗生素的种类和浓度、温度等)时，将在两个尺度上研究集群动力学。同时，将开发一个数学模型，以找出由于蜂群运动而导致阻力增加的物理机制。最后，研究将集中在单细胞水平上的化学应激反应，这将决定畜群接触抗生素的历史。

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.