Grant: Doctoral: Vanier Canada Graduate Scholarships

The foodborne pathogens enterohemorrhagic and enteropathogenic Escherichia coli (EHEC, EPEC) result in severe diarrheal disease and cause significant morbidity and mortality worldwide. In Canada, EHEC causes an estimated 50 000 infections per year, numerous deaths, and a heavy financial burden. EPEC outbreaks have occurred in Canadian childcare centres. The proposed bio-medical study aims to understand human cellular functions and how they are influenced and disrupted by EHEC and EPEC infection; this understanding is vital to prevent and treat future infections. Studying how the proteins of human cells are altered during infection (the "proteomics" of infection) can further our understanding of how these bacteria affect entire protein networks and how human cells respond to infection. TAILS (terminal amine isotopic labeling of substrates) is a new proteomics technique that not only identifies and quantifies human proteins but also characterizes how they have been modified (i.e. fragmentation or the addition of chemical groups). The proposed research will use TAILS to study EHEC and EPEC infection of human cells cultured in Petri dishes to see how human protein networks have been altered. I hypothesize that altered human proteins are important during infection and that their study will provide valuable insight into the molecular and system-wide mechanisms by which EHEC and EPEC cause human disease. This research involves a strong collaboration between the TAILS developers and one of the leading Canadian research groups studying bacterial pathogenesis and host-pathogen interactions, forming a uniquely capable group for this project. This study has broad applications to the fields of molecular microbiology and innate immunology, specifically examining how pathogens like EHEC and EPEC cause human disease and how the human cells respond to bacterial infection. This study could also reveal clinical targets against pathogenic E. coli.