An investigation into the regulation of virulence factors by DNA supercoiling in gastrointestinal pathogens (360G-Wellcome-099828_Z_12_Z)

DNA supercoiling is a global regulator that plays a critical role in the regulation of virulence factors in many gastrointestinal pathogens including S. Typhimurium. Studies of Campylobacter jejuni have revealed that there is a strong correlation between DNA Supercoiling and the regulation of different virulence genes. However C. jejuni displays an absence of many of the classic regulators of virulence found in S.Typhimurium including nucleoid associated proteins. It has recently been demonstrated that DNA supercoiling affects the regulation of motility and invasion of epithelial cells by C.jejuni. The overall aim of this project is to investigate the regulation of virulence factors by DNA Supercoiling in these two key gastrointestinal pathogens. Transcriptional profiles will be generated for S.Typhimurium and C.jejuni by RNA-seq in response to changes in DNA topology. Bioinformatic analysis of these transcriptional profiles will lead to the identification of potential DNA supercoiling regulons as well as aid the design of predictive models for identifying genes in other pathogens which are regulated by changes in DNA topology. Finally in vitro infection assays will be used to validate and functionally characterise novel supercoiling regulons identified in this analysis.