Bacterial Pathogenomics: whole-genome sequencing to investigate infection transmission, pathogenesis and antibiotic resistance (2015–2019)
My aim is to establish infectious disease research firmly in the genomic era. This Career Development Fellowship program will leverage the power of next-generation DNA sequencing to build the groundwork for personalized microbial epidemiology. By sequencing the entire genomes
of pathogenic bacteria collected from local and international clinical collections, I will investigate bacterial infectious diseases from the resolution of a single nucleotide to the scale of a global population. I will develop and use innovative bioinformatics approaches to investigate the global spread of bacterial pathogens, determine the genes that are responsible for virulence, and trace the global dispersal of new antibiotic
resistances. I will also examine in great detail the mechanisms by which pathogenic bacteria exchange DNA and attempt to unravel the evolutionary steps that lead to the emergence of new, or more virulent pathogens. Finally, I will employ new frontier technology to determine, on a whole genome scale, how methylation of DNA influences regulation and evolution of bacterial pathogens. The conceptual framework for this project rests on a deeper understanding of these mechanisms in bacterial pathogens that are under intensive study in my group: Shiga-toxin producing Escherichia coli (STEC) and uropathogenic E. coli (UPEC). Their lifestyles (e.g. reservoirs, transmission, global dissemination) and mechanisms of pathogenicity (e.g. adhesion, toxins, secretion) offer contrasting paradigms of the evolutionary paths to infectious disease. In common, however, is the continual emergence of new and evolving strains that pose a direct threat to public health.