Molecular cell biology of Leishmania
We study single-celled parasites called Leishmania, which cause disease in humans and animals in over 88 countries around the world. Leishmaniasis is a neglected disease, associated with poverty and conflict. There is currently no vaccine and an urgent need for better drug treatments.
Leishmania are transmitted by blood feeding sand flies and in the mammalian host they enter macrophages of the host and replicate intracellularly. In the Gluenz Lab we study the molecular cell biology of this parasite to understand how it can cycle between insect vector and mammalian host and how the parasites modulates host-cell functions to survive in macrophages.
Our research 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. Identification of genes and pathways important for survival in a macrophage. 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 differences in gene expression patterns between the different parasite forms and we now seek to investigate their functions.
3. Development of genetic tools. We have developed a CRISPR-Cas9 high throughput genome editing toolkit for Leishmania and related protists and are using these tools to harness the information from genome, transcriptome and proteome data and dissect the cell biology of Leishmania.
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PLoS Pathogens 11:e1005186.
Nat Commun 6:8964
Methods Cell Biol 127: 509-42
Trends Parasitol (8): 373-9