Grant: Operating Grant

The Leishmaniases are a group of infectious diseases caused by parasites belonging to the genus Leishmania. According to the World Health Organization there are 12 million current infections worldwide and two million new cases occur every year (Leishmaniasis Control, www.who.int/health-topics/leishmaniasis). Leishmaniasis is mainly found in tropical and sub-tropical regions around the globe. Like many neglected diseases, it is primarily endemic to developing nations and thus presents additional socio-economic burdens to already impoverished people. Leishmania parasites invade human macrophages, cells that normally resist infection. A Leishmania infection will prevent a macrophage cell from generating its normal arsenal of microbicidal compounds, allowing the parasites to survive, replicate, and subsequently infect neighboring cells. As of yet, few mechanistic explanations for this phenomena have been reported. However, our recent studies have shown that leishmania parasites release proteins by packaging specific proteins within small vesicles inside the cell. These vesicles and their cargo are then released from the cell as microvesicles. This research proposal includes aims to identify the proteins that are contained in these vesicles, what lipids make up these vesicles, and finally, what appearance these vesicles take on. In addition, we are proposing research to investigate if these vesicles can deliver their cargo to infected macrophages. Lastly, we plan to determine if any of the proteins secreted by leishmania parasites, both those packaged in microvesicles and those potentially released by some other mechanism, help the leishmania parasite in preventing the macrophage from producing its arsenal of microbicidal compounds. This research will greatly improve the current understanding of leishmania biology and pathogenesis, and has the potential to aid in the discovery and development of novel drugs and therapeutics.