Our project focuses on discovering new genetic mechanisms that contribute to pulmonary tuberculosis (TB), which causes disease and death in millions of people each year. We will use three novel strategies. The first is a new experimental mouse population that closely models the human population. The second is the use of computer algorithms to study traits of granulomas (aggregations of cells that are a hallmark of TB) and sites of lung damage. Third, we will integrate the complex data into testable models of TB. This research will allow us to identify genes that contribute to TB susceptibility and to improve understanding of the body's response to this deadly disease.
Update: We are the first to show that the experimental mouse population we are using contains a remarkable spectrum of responses to TB, with mice that are highly susceptible and those that are relatively resistant to infection. We published the first report of M. tuberculosis infection in this experimental mouse population and showed we could predict the disease susceptibility category with 77 percent accuracy using three molecular indicators. Now we are focusing on increasing the amount of data that we have acquired to study gene expression profiles in the lungs of super susceptible, susceptible, resistant and non-infected mice.