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Investigation of Mechanisms Underlying African Trypanosome Social Behavior


African trypanosomes, including Trypanosoma brucei and related subspecies, are the causative agents of sleeping sickness in humans and nagana in cattle. These parasites are the source of significant human mortality and limit economic growth throughout sub-Saharan Africa. T. brucei has a complex life cycle with phases in an insect vector and a mammalian host. Although motility through fluids and on tissue surfaces is central to T. brucei development and disease pathogenesis, a complete description of how the parasite moves through fluids and behave on surfaces is not available. Through the use of novel techniques and classical molecular approaches applied towards the study of T. brucei motility in suspension media and on surfaces, we have discovered unappreciated aspects of protozoan parasite biology.

Though the use of high-speed imaging, we found that that T. brucei moves through suspension media via the propagation of kinks generated by the parasite's ability to alternate the chirality of its rotation. The observation that T. brucei moves by generating alternating chiralities disproved the 150 year long notion that the parasite moves by spiraling in one direction and demonstrates that high-speed imaging can be a useful tool for uncovering important features of microorganism locomotion.

By studying T. brucei on agarose plates, we discovered that T. brucei engages in social behavior when exposed to surfaces: an unprecedented finding in protozoan parasite biology. This social behavior, termed Social Motility (SoMo) is characterized by the formation of multicellular communities that engage in polarized migrations across the agarose surface and cooperate to divert their movements in response to external signals. Investigation of the mechanisms underlying this social behavior revealed a novel role for a unique family of receptor-like proteins that were previously uncharacterized and implicates a role for cAMP signaling in the regulation of SoMo.

Lastly, our search for extra cellular factors that regulate this social behavior has led to the discovery of inter-kingdom cross-talk between T. brucei and bacteria. In short, the investigations presented here have uncovered novel aspects of T. brucei behavior that have transformed our understanding of protozoan biology and will serve as the basis for future investigations.

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