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Dr. Josie Clark-Curtiss is striving to understand the mechanisms by which M. tuberculosis causes TB. Research in her lab is directed toward understanding the genes and gene products of M. tuberculosis that are important to the intracellular survival and growth of the bacteria when they are in human macrophages. Current areas of research include:

• Identification and characterization of genes from M. tuberculosis that are differentially expressed by the bacilli when they are actively growing within human macrophages, using the selective capture of transcribed sequences (SCOTS) technique developed in the Clark-Curtiss lab.
• Analysis of the regulation of mycobacterial gene expression in response to the environment of the human macrophage phagosome
• Mutagenesis of specific genes identified in the above studies and analysis of the effects of such mutations on the ability of M. tuberculosis to survive in human macrophages and in animal infection models.
• Development of an effective vaccine against M. tuberculosis.

Dr. Clark-Curtiss is collaborating with Dr. Roy Curtiss to develop a prime-boost immunization regime for an anti-TB vaccine by employing the recombinant attenuated Salmonella vaccine systems to express M. tuberculosis antigens and to deliver the antigens to optimal sites within immunized individuals to generate protective immune responses against the tubercle bacilli. The central idea of this strategy is to stimulate induction of a primary cellular (T-cell) immunity with bacterial and viral vectors which deliver the Mtb antigen and then boosting to cause expansion of the T-cell clones induced in the prime immunization by administering the same antigen delivered in the prime immunization when produced in plants. In this way, the boost immunization only expands the desired immune response to the Mtb antigen and not to vector (bacterial or viral) antigens. There is no other team that can develop this very promising strategy as well as the researchers in the CIDV.