Bacteria secrete virulence factors in order to commandeer host cells and evade our immune system. Coombes lab researchers use cutting-edge technologies in quantitative proteomics, functional genomics and structural biology to understand the molecular mechanisms of bacterial pathogenesis and the actions of virulence factors. Current projects in the laboratory in the area of bacterial pathogenesis include: regulatory and molecular study of the type 3 secretion system that delivers bacterial toxins to host cells; the evolutionary significance and biological complexity of regulatory evolution for creating phenotypic diversity within a bacterial population; and detailed examination into how bacterial pathogens sense their host surroundings and the mechanisms that link these host sensors to adaptive gene expression involved in virulence, evasion of our immune system, and ultimately, disease. This knowledge base creates opportunities for innovative drug target discovery with tangible impacts on public health.
The innate immune system is a host’s first line of defense against foreign invaders. Pathogens use sophisticated strategies to overcome the innate immune system in order to colonize, establish a host niche, and transmit to new hosts. We have embarked on a line of research to understand the components of the innate immune system involved in protection against enteric pathogens such as Salmonella, pathogenic E. coli, and bacteria associated with Crohn’s disease.
Since drug resistance continues to erode the efficacy of conventional antibiotics against many serious bacterial pathogens, one approach to bridging a widening innovation gap in anti-infectives involves harnessing the innate immune defenses of the susceptible host. The first step is understanding the host pathways involved in susceptibility and resistance to infection. Coombes lab researchers are using genetic tools, in vivo imaging and immunological-based research in model systems to understand this incredibly important aspect of the host-pathogen interaction.
The incidence and prevalence of inflammatory bowel disease (IBD) in Canada are at critical levels. Today, 1 in every 150 people has IBD, making it a national health priority. The need to understand the root origins of this disease and to use this information to invigorate a new pipeline of treatments and preventions has never been more pressing. It is now accepted that Crohn’s disease, a major form of IBD, is an inflammatory disease driven by microbes in our gut. However, mechanisms by which pathogenic or commensal microbes work in concert with each other and with host factors to drive this inflammation are not well known.
Coombes lab scientists are conducting basic research and working with the private sector to understand the microbes that drive chronic inflammation during Crohn's disease, with a particular focus on adherent-invasive E. coli that are linked to Crohn's disease in humans. Using cell and animal models, we are understanding how the host responds to AIEC over chronic timescales. With investment in this area, breakthrough research with direct applications to clinical practice and public health can be expected.