Robert Potter Rose Hills
Understanding the Effects of AKT Pathway Inhibitors on the Pathogenesis of Mycobacterium Tuberculosis in Macrophages
Mycobacterium tuberculosis manipulates the host response to prevent bactericidal mechanisms and promote its own survival. AKT is one enzyme that has been linked to proliferation of M. tuberculosis within its target. As a serine/threonine protein kinase, AKT is an important enzyme in signal transduction pathways for apoptosis. Inhibition of AKT during infection leads to increase bacterial death. By looking at the downstream effects of the AKT pathway, our goal is to determine, why? This will be accomplished by using site directed mutagenesis to create multiple alterations to the structure of AKT in macrophages and then using inhibitors of AKT, stop the downstream effects at numerous junctures after being infected by a model organism, M. Smegmatis. Western blotting will be used to analyze the AKT signaling. We plan to infect the AKT mutant macrophages with fractionated M. tuberculosis and treat with inhibitors to compare to infection patterns of M. Smegmatis.