Functional analysis of immune-modulatory Salmonella virulence proteins

免疫调节沙门氏菌毒力蛋白的功能分析

• 批准号: 2144804
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 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=studentship-2144804
• 关键词: Functional; analysis; immune; modulatory; Salmonella

Salmonella enterica serovar Typhimurium, an intracellular bacterium that causes gastroenteritis in humans, uses type III secretion systems (T3SS) to deliver virulence "effector" proteins in to the host cell. These effectors display remarkably sophisticated mechanisms to specifically and potently interfere with host cell signalling. This work will focus on the function of poorly characterised effectors that modulate innate immunity including interferon and Wnt/b-Catenin signalling. To study the physiological function of selected effectors we will combine various techniques including microbiological infection assays and biochemical co-immunoprecipitation techniques combined with mass spectrometry in order to identify protein targets. RNAseq following infection with Salmonella mutants will be used to investigate the transcriptional consequences of the effector under investigation. To complement this approach, structural biology will be used to analyse protein function in molecular detail. As multi-drug resistant bacterial strains represent a significant problem, intensive research into the mechanism of Salmonella virulence is of great importance.

鼠伤寒沙门氏菌是一种引起人类胃肠炎的细胞内细菌，它使用III型分泌系统(T3SS)将毒性“效应器”蛋白输送到宿主细胞中。这些效应器表现出非常复杂的机制，专门和有力地干扰宿主细胞的信号传递。这项工作将集中在调节天然免疫的特征不佳的效应器的功能上，包括干扰素和Wnt/b-catenin信号传递。为了研究选定的效应子的生理功能，我们将结合各种技术，包括微生物感染分析和生物化学共沉淀技术，并结合质谱学，以识别蛋白质靶标。感染沙门氏菌突变体后的RNAseq将被用于研究被调查的效应器的转录后果。为了补充这一方法，将使用结构生物学来详细分析蛋白质的分子功能。由于多重耐药菌株是一个重要的问题，深入研究沙门氏菌的毒力机制具有重要意义。