Biology Seminar by Christopher de Graffenried (Brown University)
SENG113
Genevieve Kozak
Trypanosomatids cause a range of deadly diseases, including Human African Trypanosomiasis (HAT), Chagas, and Kala-azar, which impact millions of people worldwide. These parasites undergo significant changes to their cell morphology to adapt to the varying environments they encounter within their mammalian hosts and insect vectors. A sheet of microtubules, known as the subpellicular microtubule array, underlies the parasite plasma membrane and drives cell morphogenesis. Very little is known about how the subpellicular array is organized and duplicated during cell division, partly because the tight arrangement of the microtubules and their helical twist make it difficult to image the array in its entirety. The molecular components of the array also remain uncharacterized. Using a range of biochemical and imaging approaches, we have now created the first reconstructions of full subpellicular microtubule arrays in Trypanosoma brucei, the causative agent of HAT. These reconstructions provide key information about how the subpellicular array shapes these parasites and how it is inherited during cell division, exemplifying how highly divergent parasites have specialized components of the core eukaryotic toolkit to suit their specific needs, selected by a very different evolutionary trajectory than that of better-studied organisms. These uniquely configured pathways could be potential avenues for drug discovery, which is sorely needed.