The role of RNA elements that control flagellar biosynthesis during infection

感染过程中控制鞭毛生物合成的RNA元件的作用

• 批准号: 2279408
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2279408
• 关键词: role; RNA; elements; control; flagellar

PhD project strategic theme: Understanding the rules of lifeUnderstanding host responses to pathogen infection is critical for guiding the development of intervention strategies. Changes in gene expression are commonly observed upon infection, as exemplified by numerous transcriptomic studies. However, techniques to analyse genome-wide responses at the level of protein synthesis have only recently become available with ribosome profiling, permitting a more sophisticated interrogation of host-pathogen interaction at the level of translation.This project will focus on the synthesis of flagellin in the food-borne enteric pathogen Salmonella enterica Typhimurium. Flagellin is a major virulence factor as it helps the bacterium swim to its preferred site of infection inside the host and is also a key antigen for the host innate immune system. The flagellar filament consists of thousands of copies of flagellin monomer protein. Salmonella undergoes phase-switching to produce two types of flagellin-FliC in phase 1 or FljB in phase 2-with each phase being beneficial in different circumstances. Indeed, it was shown that while phase 2 flagella confer a motility advantage in highly viscous liquids (Yamaguchi et al., 2020, Biomolecules), phase 1 has a selective advantage in gastrointestinal colonization as well as systemic infection (Horstmann et al., 2017, Cellular microbiology; Ikeda et al., 2001, Infection and Immunity). This alternative expression of the two flagellins is achieved by control of the fljBA operon, which encodes FljB and FljA. The repressor protein FljA controls expression of the distally located fliC through direct binding of fliC 5' UTR, direct-ly impeding FliC synthesis (Aldridge et al., 2006, PNAS; Yamamoto & Kutsukake, 2006, Jour-nal of Bacteriology). However, the exact role of the 5' UTR in fliC expression is less clear, and whether FljA regulates other mRNAs in a similar manner is unknown. In addition to addressing these unknowns, the project will investigate how gene expression is regulated during Salmonella infection.

博士项目战略主题：了解生命的规则了解宿主对病原体感染的反应对于指导干预策略的制定至关重要。感染后通常观察到基因表达的变化，如许多转录组学研究所示。然而，在蛋白质合成水平上分析全基因组反应的技术最近才出现在核糖体分析中，允许在translation.This项目的水平上对宿主-病原体相互作用进行更复杂的询问，该项目将侧重于食源性肠道病原体沙门氏菌的鞭毛蛋白的合成。鞭毛蛋白是一种主要的毒力因子，因为它帮助细菌游到宿主体内的首选感染部位，也是宿主先天免疫系统的关键抗原。鞭毛丝由数千个鞭毛蛋白单体蛋白拷贝组成。沙门氏菌经历阶段转换以产生两种类型的鞭毛蛋白-第1阶段的FliC或第2阶段的FljB-每个阶段在不同情况下都是有益的。事实上，已经表明，虽然2期鞭毛在高粘性液体中赋予运动性优势（Yamaguchi等人，2020，Biomolecules），1期在胃肠道定殖以及全身性感染中具有选择性优势（Horstmann等人，2017，细胞微生物学; Ikeda等人，2001，感染和免疫）。两种鞭毛蛋白的这种交替表达通过控制编码FljB和FljA的fljBA操纵子来实现。阻遏蛋白FljA通过直接结合fliC 5' UTR控制远端定位的fliC的表达，直接阻碍FliC合成（阿尔德里奇等人，2006，PNAS; Yamamoto & Kutsukake，2006，细菌学杂志）。然而，5' UTR在fliC表达中的确切作用尚不清楚，FljA是否以类似的方式调节其他mRNA也是未知的。除了解决这些未知问题外，该项目还将研究沙门氏菌感染期间基因表达如何调节。