Grant: Doctoral Research Award: PA -General Pandemic Prepared./Health Emergen. Research

Tuberculosis (TB) is caused by the bacteria Mycobacterium tuberculosis (Mtb) and remains a serious health problem worldwide, causing over 1 million deaths each year. Current treatments can take many months to years and with the rise of antibiotic resistance, makes it even more difficult to treat. Mtb has evolved many methods to evade the immune response, allowing it to survive in the body. For instance, Mtb can destroy and escape the compartments within our immune cells that normally function to contain and kill the bacteria. This damage is then recognized by the cells and promotes increased production of various inflammatory proteins. Our studies have identified the MX protein family as one such class of proteins that is highly elevated during Mtb infection. MX proteins have been shown to control viral infections but have not been studied in the context of bacterial infections. Recent studies have shown that MX proteins play a key role in preserving the integrity of the compartments that contain viruses or bacteria. Hence, the proposed project will study the role of MX proteins during Mtb infection. Specifically, I will examine the mechanisms by which MX proteins function to protect or harm our immune cells from Mtb invasion using genetically engineered immune cells with different levels of MX protein. Furthermore, I will use a labelling system that can identify proteins that interact with and facilitate the function of MX proteins. Identifying protein-protein interactions is crucial to understanding the potential function of MX during tuberculosis infection. Overall, I expect this research will reveal and characterize proteins that could be harnessed for new therapeutics to help overcome this deadly lung disease.