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The diseases - leishmaniasis and trypanosomiasis
Both Leishmania and trypanosomes have a complex life cycle in which they are transmitted by an insect vector between mammalian hosts. Leishmania causes a range of different diseases from the severe and fatal visceral leishmaniasis to the self-healing cutaneous leishmaniasis and is found throughout the tropics and into the southern Mediterranean. Trypanosoma brucei on the other hand is restricted to sub-Saharan Africa, where it causes the fatal disease African sleeping sickness.
Understanding cell morphogenesis
The distinctive shape of Leishmania and trypanosomes is formed by a corset of cross-linked microtubules that are just beneath the cell membrane. Both organisms have a flagellum that provides the propulsive force that enables them to move and unusually this flagellum is laterally attached to the side of the cell body. In Leishmania this attachment region is very short, whereas in trypanosomes the flagellum is attached for the majority of its length. The attachment of the flagellum is mediated by a large complex cytoskeletal structure called the Flagellum Attachment Zone, which forms a seam in the microtubule array. Assembly of the Flagellum Attachment Zone is a key step in cell morphogenesis and disruption of this process leads to dramatic changes in cell shape and form. The aim of the lab is to understand the role of the Flagellum Attachment Zone from its individual components to how they interact and assemble and how this influences cell morphology. To do this we use a range of modern molecular cell biology techniques combined with both light end electron microscopy.
Genetic technology development
Leishmania and trypanosomes are excellent organisms to work with as they are extremely amenable to genetic manipulation. A continuing theme of the lab is to build new genetic tools for our own work and the rest of the kinetoplastid parasite field. Most importantly, this work has led to development of a high-throughput endogenous gene tagging project in which every protein encoded in the trypanosome genome is being tagged with a fluorescent protein. The resulting cell line is being imaged and those images are being put on a website. This technology is now being used to develop further high-throughput screens in the lab.