Grant: Banting Postdoctoral Fellowship Program

Tuberculosis (TB) is a chronic infectious disease caused by the human pathogenic bacterium Mycobacterium tuberculosis (Mtb). Even in Canada TB is still a major health concern, especially for inner city poor, newly arrived immigrants, and aboriginal people. The increasing occurrence of multiple drug resistant forms of Mtb (including the untreatable XDR forms) in countries that provide the majority of new immigrants to Canada makes tuberculosis an important issue for the average Canadian. The critical role of human genetic factors in the progression from infection with Mtb to clinical TB has been established. Moreover, there is inter-individual variability at the initial step of the infectious process, as ~20%-50% of exposed persons appear to be naturally resistant to infection by Mtb. In contrast to the study of clinical TB, the dissection of the molecular basis of resistance to infection has received little attention. During my graduate program I have collaborated to build up large family datasets in different endemic areas of tuberculosis. Specifically, I have focused on the investigation of immune tests that are used clinically to establish infection with Mtb, and this work has validated the importance of human genetic factors for infection with Mtb. My postdoctoral studies, employing highly statistical methods of genetic analysis in conjunction with state-of-the-art genomics technologies, will now focus on the mapping of genomic regions impacting on anti-TB immunity and on the molecular isolation of gene variants that make a person innately resistant to infection with Mtb. Understanding innate resistance to infection is key to the prevention of TB in immune suppressed patients and to the control of outbreaks of XDR TB, since without infection no TB disease can develop. Hence, my postdoctoral work will have enormous impact for one of the most pressing global health problems.