Molecular cell biology of Leishmania
Leishmania are protozoan parasites, transmitted by sand flies, which cause a spectrum of disease, ranging from potentially disfiguring cutaneous lesions to life threatening systemic infections. Leishmania parasites have two principal life cycle stages: promastigote forms in the sand fly and amastigote forms that replicate in mammalian phagocytes. Much remains unclear about the molecular and cellular mechanisms that enable Leishmania parasites to subvert macrophage defence mechanisms and cause disease.
Research in the Gluenz lab focuses on three main areas.
1. Structure and function of the Leishmania flagellum. Cilia and flagella are cellular projections built around a microtubule axoneme whose molecular architecture is highly conserved across eukaryotes. When the Leishmania parasite is engulfed by a macrophage, it changes shape and the flagellum turns from a device built for swimming (with a 9+2 arrangement of axoneme microtubules), into a structure resembling a sensory cilium (with a 9+0 axoneme). We aim to dissect the mechanisms that govern this change in flagellar structure and test our hypothesis that the amastigote flagellum serves as a sensory organelle in host-parasite interactions.
2. We used RNA-sequencing to map gene expression patterns in the insect- and mammalian-infective forms of Leishmania mexicana. Comparative analyses allowed us to define changes in gene expression patterns associated with the changes in cell morphology and we now seek to identify genes and pathways important for survival in a macrophage.
3. Developing genome editing tools to harness the information from genome, transcriptome and proteome data and dissect the cell biology of Leishmania. Recent work includes development of a rapid CRISPR/Cas9-based method for genome editing in Leishmania and related parasites.
PLoS Pathog 11(10): e1005186
Nat Commun 6: 8964
Methods Cell Biol 127: 509-42
Trends Parasitol (8): 373-9
FASEB J 24: 3117-21