Research Fellows Directory
Dr Eva Gluenz
University of Oxford
Leishmania are parasites that are transmitted by the bite of sand flies and live in human blood cells, the macrophages, where they cause disease. Surviving inside a macrophage is quite a remarkable feat – macrophages are equipped to kill pathogens and normally protect the body from infection. How are Leishmania parasites manage able to hijack the macrophage for their own purpose?
Leishmania are single cells with a thin projection, called the flagellum. In the sand fly they use it to attach themselves securely to the fly and to swim from the gut to the mouthparts to reach their next host. The parasite changes its shape when it enters human cells and it was long thought that the flagellum was unimportant inside the human cell. We now know that flagella can be very important ‘cellular antennae’ for receiving and transmitting signals and I showed previously that the flagellum of intracellular Leishmania resembles a specific type of cellular antenna called a primary cilium.
Over the past year, we used powerful new electron microscopy methods to build 3D models of Leishmania and their flagellum inside macrophages. These models revealed interesting new information about the connections between host cell and parasite and pointed to ways in which the parasite could deliver “messages” to manipulate the behaviour of the host cell.
To pinpoint parasite genes needed for infection, we developed a method that enables us to remove genes from the parasite quickly so that we can test whether the resulting mutant parasites can survive in host cells. We produced a collection of mutant parasites where we removed building blocks of the flagellum and we are now doing experiments to test whether these parasites can still infect and hide in human cells. Our method can also be applied to many other questions about the biology of parasites; many and laboratories around the world are now using our tools to study how these pathogens are able to cause disease.
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