Structural characterization of the bacterial flagellum basal body

细菌鞭毛基体的结构特征

基本信息

批准号：
BB/R009759/1
负责人：
Julien Bergeron
金额：
$ 62.25万
依托单位：
University of Sheffield
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FR009759%2F1
关键词：
Structural characterization bacterial flagellum basal

项目摘要

Many bacteria utilize a long, rotating filament on their surface, called the flagellum, to swim in their surrounding environment, and for adherence to solid surfaces. In particular, these features are essential for many pathogenic bacteria such as E.coli, Salmonella, Shigella etc.. to cause disease. This is because the flagellum allows them to spread in the host's body, and to adhere to their cells, as well as to medical devices such as catheters. As a consequence, understanding the bacterial flagellum at the molecular level could have numerous medical implication, and disrupting its rotation and adherence properties would largely reduce infection in a clinical setting. However, the flagellum is a very sophisticated nano-machine, and studying its mechanism of action at the molecular level is particularly challenging. A central region of the flagellum, called the "basal body", serves as an anchoring point around which the complete machinery forms. Despite the importance of this region, we know very little about its molecular details, and about how its constituting components come together to form a stable platform around which the flagellum assembles. The objective of the proposed research is to use advanced biophysics methods, including the most cutting-edge electron microscopy techniques, to generate a molecular "map" of the flagellum basal body. We will then exploit this map to determine how its constituting components come together to form such a sophisticated structure. These results could be exploited to generate new therapies that block the formation or function of the flagellum. This would be of particular interest because the flagellum is widespread amongst bacteria, and therefore such therapy could target infections from a wide range of bacteria. In addition, a molecular map of the basal body will provide clues of how bacteria were able to "evolve" structures such as the flagellum, by comparison to other known nano-machines. Finally, understanding how the flagellum forms could be used to develop motile drug delivery systems, which could be exploited for a wide range of medication such as anticancer treatment or gene therapies.

许多细菌在其表面上使用长长的旋转细丝，称为鞭毛，在周围的环境中游泳，并遵守固体表面。特别是，这些特征对于许多致病细菌，例如大肠杆菌，沙门氏菌，志贺氏菌等都至关重要。这是因为鞭毛允许他们散布在宿主的体内，并粘附在其细胞中，以及诸如导管等医疗设备。结果，了解分子水平的细菌鞭毛可能具有许多医学意义，并且破坏其旋转和粘附特性将在很大程度上减少临床环境中的感染。但是，鞭毛是一种非常复杂的纳米机器，研究其在分子水平上的作用机理尤其具有挑战性。鞭毛的一个中央区域，称为“基体”，是一个完整机械形成的锚固点。尽管该区域的重要性很重要，但我们对其分子细节的了解知之甚少，以及其构成组件如何融合在一起形成一个稳定的平台围绕鞭毛组装。拟议研究的目的是使用先进的生物物理学方法，包括最先进的电子显微镜技术，以生成鞭毛基体的分子“地图”。然后，我们将利用这张地图，以确定其组成组件如何组合在一起形成这样复杂的结构。可以利用这些结果来生成阻断鞭毛的形成或功能的新疗法。这将引起人们的关注，因为鞭毛在细菌中广泛存在，因此这种疗法可以靶向各种细菌的感染。此外，与其他已知的纳米机器相比，基础体的分子图将提供细菌如何“进化”结构（例如鞭毛）的线索。最后，了解如何使用鞭毛形式来开发运动性药物输送系统，该系统可以用于多种药物（例如抗癌治疗或基因疗法）。