Functional analysis of immune-modulatory Salmonella virulence proteins

肠炎沙门氏菌血清型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）将毒力“效应”蛋白输送到宿主细胞中。这些效应器显示出非常复杂的机制，可以特异性和有效地干扰宿主细胞信号传导。这项工作将重点关注包括干扰素和Wnt/b-Catenin信号传导在内的调节先天免疫的特性不佳的效应物的功能。为了研究选定的效应物的生理功能，我们将结合各种技术，包括微生物感染测定和生化共免疫沉淀技术结合质谱法，以确定蛋白质靶点。感染沙门氏菌突变体后的RNAseq将用于研究所研究的效应物的转录后果。为了补充这种方法，结构生物学将用于分析蛋白质的分子功能细节。由于多重耐药菌株是一个重大问题，深入研究沙门氏菌的毒力机制具有重要意义。

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.