Integration of Developmental Pathways by Methylation to Control Immunity to Intestinal Infection

Brief Summary of ERC proposal: The gastrointestinal tract is a common site for infection by a variety of pathogens. For example, gut-dwelling parasitic worms currently infect over a billion people, mostly in developing nations. In addition, food-borne bacterial infections such as enterohemorrhagic Escherichia coli that can cause fever, vomiting, and severe diarrhea remain an important public health concern. We have too little insight in how these pathogens are causing disease and how immunity to them is regulated. The intestinal epithelium plays a crucial role in pathogen resistance. It can respond to immune-cell signals to neutralize pathogens, and it shapes immune-cell responses by secreting signals itself. It is currently unknown how these epithelial functions are regulated. I propose that the Wnt and Hippo pathways, which are established regulators of embryonic development, play a crucial role in epithelial responses to pathogens. Summary to improve application: There were three specific weaknesses noted by the different reviewers. 1. I have little supervision and lab leader experience. 2. Limited experience with cutting edge techniques that I propose to do. 3. Alternative explanations for my preliminary data in addition to my hypothesis. I plan to improve these things by attending an EMBO Lab Management course, this will improve my profile as a supervisor and provides training to lead a lab. In addition, I propose to do a set of high profile experiments, using cutting edge techniques, to put in the preliminary data of my new proposal that will also address alternative hypotheses.