Functional analysis of immune-modulatory Salmonella virulence proteins

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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.