Research Summary

March 2004

The overarching interest of our group is the nature and consequences of genetic diversity among Mycobacterium tuberculosis. This interest is being pursued through three general approaches.

1)   Integrating molecular and conventional epidemiology to understand the contemporary transmission dynamics and pathogenesis of tuberculosis. This approach is being utilized in a broadly collaborative structure in San Francisco since 1990 involving the Division of Tuberculosis Control, San Francisco Department of Public Health, the Division of Pulmonary and Critical Care Medicine and the Chest Service at San Francisco General Hospital, University of California, San Francisco (UCSF), and the Francis J. Curry National Tuberculosis Center . We also work in collaboration with investigators from Mexico's National Institutes of Public Health (INSP) and Nutrition (INCMNSZ) to apply these techniques in a community in the state of Veracruz, Mexico.

2)   Exploiting detailed molecular epidemiologic observations to understand the consequences of genetic diversity for the behavior of M. tuberculosis in human populations. In particular, we are pursuing the hypothesis that many of the clinical and epidemiologic manifestations of tuberculosis may be a consequence of phenotypic properties (such as transmissibility and tissue tropism) which are specifically associated with particular strains of M. tuberculosis.

3)  Using population genetic and microbial evolutionary principles to understand the factors that shape the genetic diversity of natural populations of M. tuberculosis. These projects entail the use of DNA microarrays to characterize the variability in genomic content and then reconstruct phylogenetic analysis. Work completed thus far has identified significant genetic contrasts between M. tuberculosis and the family of BCG vaccines, which has implications for diagnostics and vaccine development. Current efforts are extending these techniques to populations of M. tuberculosis from different geographical areas.

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Last updated Feburary 6, 2004