Biomechanics of the Swimming and Chemotaxis of the Leptospiraceae

钩端螺旋体科游泳和趋化性的生物力学

• 批准号: 2309442
• 负责人: Charles Wolgemuth
• 金额: $ 58.71万
• 依托单位: University of Arizona
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2309442&HistoricalAwards=false
• 关键词: Biomechanics; Swimming; Chemotaxis; Leptospiraceae

This award will support research that will improve our understanding of physical aspects of bacteria. Specifically, this work will focus on the bacterium Leptospira interrogans, which is highly invasive. Relatives of this bacterium cause diseases such as Lyme disease and syphilis. This work will explore how specific proteins in the bacterium influence its physical structure and movement, how the bacterium interacts with mammalian-like tissues, and how the bacterium controls its ability to navigate through its hosts. The results of this work will reveal why this bacterium is so efficient at invading mammals and creating infections in them. This work is interdisciplinary, and will use techniques from physics, microbiology, cellular biology, bioengineering, and mathematics. Insights gained from this work will provide new information about the disease processes of this bacterium and related species and may eventually lead to novel therapeutics. The interdisciplinary approach will help broaden participation of underrepresented groups and will be used as an outreach opportunity for lower socio-economic K-12 students at schools in the Tucson area.Spirochete bacteria are long and thin and can propel themselves through fluids and tissues with surprising ease. This motility is driven by internal helical flagella that rotate in between the cell wall and the outer membrane. While past research elucidated some basic mechanisms of spirochete motility, many questions remain elusive. This research examines the bacterium that causes leptospirosis as it has a single flagellum at either end of the cell, thereby allowing direct analysis of the direction of rotation of the flagella and how it is impacted by different alterations and perturbations, while also providing a comparative analysis for previous work that has been done on the Lyme disease spirochete. Specifically, this research will assess the specific role of biophysical parameters and proteins on motility, determine the effect of external environment on movement, and determine whether mechanical cues are involved in chemotaxis. The research will use live cell imaging, optical trapping and other micromanipulation techniques, and computational modeling to explore the general hypothesis that biophysical interactions between the flagella and cell body are a crucial aspect of this bacterium’s ability to invade and infect mammalian hosts.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该奖项将支持有助于提高我们对细菌物理方面的理解的研究。 具体来说，这项工作将集中在细菌钩端螺旋体问号，这是高度侵入性。 这种细菌的亲戚会引起莱姆病和梅毒等疾病。 这项工作将探索细菌中的特定蛋白质如何影响其物理结构和运动，细菌如何与类梭菌组织相互作用，以及细菌如何控制其在宿主中导航的能力。 这项工作的结果将揭示为什么这种细菌在入侵哺乳动物并在其中造成感染方面如此有效。 这项工作是跨学科的，将使用物理学，微生物学，细胞生物学，生物工程和数学的技术。从这项工作中获得的见解将提供有关这种细菌和相关物种的疾病过程的新信息，并可能最终导致新的治疗方法。这种跨学科的方法将有助于扩大代表性不足的群体的参与，并将被用作图森地区学校中社会经济水平较低的K-12学生的外展机会。螺旋体细菌又长又细，可以令人惊讶地轻松推动自己穿过液体和组织。这种运动是由内部螺旋鞭毛驱动的，鞭毛在细胞壁和外膜之间旋转。虽然过去的研究阐明了螺旋体运动的一些基本机制，但许多问题仍然难以捉摸。这项研究检查了导致钩端螺旋体病的细菌，因为它在细胞的两端都有一个单一的鞭毛，从而可以直接分析鞭毛的旋转方向以及它如何受到不同的改变和扰动的影响，同时还提供了对莱姆病螺旋体先前工作的比较分析。具体来说，这项研究将评估生物物理参数和蛋白质对运动的具体作用，确定外部环境对运动的影响，并确定机械线索是否参与趋化。这项研究将使用活细胞成像，光学捕获和其他显微操作技术，和计算建模，以探索一般假设，即鞭毛和细胞体之间的生物物理相互作用是这种细菌入侵和感染哺乳动物宿主的能力的一个关键方面。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的评估来支持。影响审查标准。