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. We developed a rapid high-throughput method for CRISPR-Cas9 gene editing in Leishmania and rapid phenotyping of barcoded mutants in vitro and in vivo. Using these methods we are dissecting the role of parasite genes in infectivity and life cycle progression. We currently focus on the function of the parasite’s flagellum, which is required for swimming and attachment in the sand fly. During macrophage infection, the flagellum is remodelled to a structure resembling a sensory cilium, which may be used for host-parasite communication. Through the study of mutant phenotypes we aim to discover how this sensory-type cilium helps infection of macrophages and parasite survival. This project offers the opportunity to acquire skills in cutting edge CRISPR-Cas9 genome editing methods and bioimaging, including different 3D electron microscopy methods and fluorescence microscopy.