Mechanism of Trypanosoma brucei Movement across the Blood-Brain Barrier

Undergraduates: Noah Crees, Cheryl Jones

Faculty Advisor: Keith Burridge
Department: Biology

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I am investigating the mechanism by which the parasite Trypanosoma brucei crosses the microvascular endothelium of the blood-brain barrier (BBB) to cause Human African Trypanosomiasis. There are two stages of this disease: the acute stage is characterized by parasites confined to the blood and lymph, whereas the chronic stage is characterized by parasites aggregating in the brain parenchyma (Masocha et al., 2004). T. brucei crossing the BBB facilitates pathogenesis, disrupting circadian rhythms of sleep and is potentially fatal (CDC). While the acute stage can be treated with chemotherapy, deficient treatment for the chronic stage calls for a better understanding of how T. brucei crosses the BBB. Some studies have shed light on this mechanism, but it is not yet truly understood. In a mouse model, Mulenga et al. (2001) observed that T. brucei is able to cross the BBB without compromising endothelial tight junctions. Tight junctions exist between adjacent endothelial cells to prevent unwanted cells from passing through the BBB. In another study using mice, T. brucei has been shown to cross the BBB at the same location as lymphocytes, implying that T. brucei may employ a similar mechanism as lymphocytes use to cross during an immune response (Masocha et al., 2004). I am using immunofluorescence microscopy to observe T. brucei interactions with an endothelial monolayer in vitro, with the aim of assessing localized changes in junction proteins and cytoskeletal actin patterns.