Host-parasite interactions: the role of the Leishmania flagellum in infection

Leishmania are unicellular parasites that are transmitted by sand flies and cause important neglected diseases in humans and animals. In the mammalian host, Leishmania are taken up by phagocytic cells of the immune system and then replicate intracellularly in the phagolysosome of macrophages. A lot remains unclear about the cellular mechanisms enabling the parasites to escape destruction by the macrophage.
We are using a combination of molecular cell biology approaches to study the intracellular parasites and how they subvert host cell functions. We are particularly interested in the role of the Leishmania flagellum. In the sand fly, Leishmania use their flagellum for swimming and attachment to the fly gut. We have previously shown that during macrophage infection, the flagellum is remodelled to a structure resembling a sensory cilium, which may be used for host-parasite communication. We now would like to understand in detail how the intracellular parasite interacts with the host cell and whether its sensory-type cilium is required for infection of macrophages and parasite survival. The student will approach these questions using genetic techniques to modify or delete Leishmania genes, and biochemical and bioimaging methods to study the phenotypes of mutant parasites. This project offers the opportunity to acquire skills in cutting edge CRISPR-Cas9 genome editing methods, using tools we have developed for Leishmania, and bioimaging, including different 3D electron microscopy methods and fluorescence microscopy.