Microbiology and Systems Biology focusing on computational microbiology

这项工作的重点是使用建模和分子模拟来表征噬菌体-细菌相互作用的各个方面。由于病原菌对大多数现有抗生素具有耐药性，因此对人类、动物和植物的福利仍然是一个巨大的问题。革兰氏阴性菌周围的细胞包膜由两层膜（内膜和外膜）组成，这两层膜被称为周质的水区隔开。这三个区域共同为细菌提供了强大的防御，抵御不需要的进入分子，包括抗生素。近年来，噬菌体作为细菌的天然捕食者有可能被用于治疗目的，这一点已经变得很明显。在本项目中，基于最近在结构生物学和噬菌体蛋白及其细菌膜受体复合物的分子建模和动力学方面的工作，我们将解决以下开放性问题：1-细菌外膜受体如何通过脂多糖（LPS）的长o抗原链接近噬菌体？噬菌体蛋白的结合如何改变受体蛋白的构象动力学？天然lps -噬菌体蛋白相互作用的本质是什么？这些在不同的细菌种类中是如何变化的？学生掌握的技能：使用传统和基于人工智能的方法进行分子建模。2级分辨率的分子模拟。在一系列高性能计算架构上运行模拟的经验。具有与结构生物学家合作的能力，并能够清晰地表达emrc战略技能优先事项：定量技能，特别是在分析模拟数据，确定轨迹收敛和识别保守分子相互作用方面。具有解释结构数据和整合模型构建仿真系统的跨学科技能

This programme of work focusses on using modelling and molecular simulations to characterise various aspects of bacteriophage-bacteria interactions.Pathogenic bacteria remain an enormous problem for human, animal and plant welfare due to their resistance to most current antibiotics. The cell envelope that surrounds Gram-negative bacteria is composed of two membranes (the inner and outer) which are separated by an aqueous region known as the periplasm. Together these three regions provide the bacterium with a formidable defence against unwanted incoming molecules, including antibiotics. In recent years it has become apparent that bacteriophages, which are natural predators of bacteria have the potential to be co-opted for therapeutic purposes. In this project, building upon recent work in structural biology and molecular modelling and dynamics of bacteriophage proteins in complex with their bacterial membrane receptors, we will address the following open questions:1- How accessible are bacterial outer membrane receptors to the bacteriophage through the long O-antigen chains of lipopolysaccharide (LPS)?2- How does the binding of the bacteriophage protein alter the conformational dynamics of the receptor protein?3- What are the nature of the native LPS-bacteriophage proteins interactions? How do these vary across bacterial species?Skills gained by the student:Molecular modelling using traditional and AI-based methods.Molecular simulations at > 2 levels of resolution.Experience of running simulations on a range of High-Performance Computing architectures.The ability to collaborate with structural biologists and to articulateMRC strategic skill priorities:Quantitative skills, particularly in analysis of simulation data, determining convergence of trajectories and identifying conserved molecular interactions. Interdisciplinary skills in interpreting structural data and integrating with models to construct simulation systems