Investigating the molecular determinants of inter-bacterial competition

研究细菌间竞争的分子决定因素

• 批准号: 1914300
• 金额: --
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1914300
• 关键词: Investigating; molecular; determinants; inter; bacterial

Many bacterial pathogens use the Type VI secretion system (T6SS) nanomachine to fire toxic 'effector' proteins directly into target cells. It is becoming increasingly apparent that the T6SS plays a key role in the virulence and competitiveness of diverse Gram-negative bacteria, including important human pathogens. Many, diverse bacteria, including important pathogens, can use T6SSs to target other bacterial cells, killing or inhibiting rivals. 'Anti-bacterial' T6SSs thus provide a competitive mechanism to allow pathogens to proliferate in polymicrobial infection sites or environmental reservoirs and ultimately cause disease. Importantly, understanding the lethal consequences of T6SS anti-bacterial effectors on targeted bacterial cells offers the potential to uncover new ways to kill or inhibit bacterial pathogens. In this project we aim to determine the molecular basis of the toxicity of one or more novel anti-bacterial effectors, using a combination of genetic, biochemical, biophysical and structural approaches.1.Explain interdisciplinary interface: This project will develop my interdisciplinary knowledge and skills at the interface of bioscience-physics, as well as fundamental biochemistry. This will be conducted through purification of novel toxins, which shall enable us to evaluate their toxic activity using various biochemical assays. These toxins will also be used in attempts to crystallize and subsequently solve their structures.2.Does project require significant amount of quantitative skills? NO 3.Does project require significant amount of whole organism physiology skills? NO

许多细菌病原体使用VI型分泌系统（T6 SS）纳米机器将有毒的“效应”蛋白直接发射到靶细胞中。越来越明显的是，T6 SS在多种革兰氏阴性菌（包括重要的人类病原体）的毒力和竞争力中起着关键作用。许多不同的细菌，包括重要的病原体，可以使用T6 SS靶向其他细菌细胞，杀死或抑制竞争对手。因此，“抗菌”T6 SS提供了一种竞争机制，允许病原体在多微生物感染部位或环境储库中增殖，并最终导致疾病。重要的是，了解T6 SS抗菌效应物对靶向细菌细胞的致命后果提供了发现杀死或抑制细菌病原体的新方法的潜力。在这个项目中，我们的目标是确定一个或多个新的抗菌效应物的毒性的分子基础，使用遗传，生物化学，生物物理和结构的方法相结合。1.解释跨学科的接口：这个项目将开发我的跨学科知识和技能在生物科学-物理学的接口，以及基础生物化学。这将通过新毒素的纯化进行，这将使我们能够使用各种生物化学测定来评估其毒性活性。这些毒素也将用于结晶和随后解决其结构的尝试。2.项目是否需要大量的定量技能？项目是否需要大量的整体生物生理学技能？没有