Grant: Foundation Grant

As a doctor and a scientist, I ask why many people are exposed to the bacterium, Mycobacterium tuberculosis, but only a minority develop the disease tuberculosis (TB). To understand these variable outcomes, I have established CIHR-funded programs of research that study the spread of this bacterium (epidemiology) and the fundamental biology of the disease (looking from both the perspective of the bacterium and that of the human host). The present application brings together three themes of TB research that share conceptual and methodologic synergies. In molecular epidemiology work (theme 1), our group makes a DNA 'fingerprint' of bacteria to track chains of transmission. This information, integrated with Public Health data, will define better ways to intervene with antibiotics in settings with drug sensitive and multidrug resistant settings. In bacteria-based studies (theme 2), our group compares the bacteria that causes TB with related bacteria that live in the environment and do not cause a contagious disease. These studies will uncover bacterial targets to neutralize in a new vaccine. In host-based studies (theme 3), our group studies how a part of the immune system, called innate immunity, recognizes Mycobacterium tuberculosis and how this translates into effective control of the infection. These studies will define host responses to be enhanced by a new vaccine. Together, these studies, carried out at the level of human populations and within a laboratory setting, will identify critical bacterial- and human-determinants of disease. I am one of very few TB researchers in the world who has the necessary training and a track record of success to lead this combination of studies. The information gained will drive the best application of existing antibiotics, to better control TB, and inform the development of a new vaccine, to eliminate TB.