The molecular basis and evolution of host-parasite interactions in African trypanosomes

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African trypanosomes are single-celled parasites that live in the bloodstream of mammals in sub-Saharan Africa and are passed between mammals though the bite of the tsetse fly. Several species of trypanosome lead to disease in cattle and other livestock, resulting in loss of productivity for farmers. The disease is a huge economic burden in affected areas, leading to reduced life chances for families in rural Africa. One of these trypanosome species is able to infect humans and causes a lethal disease. Currently drug treatments are inefficient and toxic. The parasite acquires nutrients from their host, avoid killing by the host immune system and adapt to the different mammals they can infect. Through my research I would ultimately like to understand, and then interfere, with the way in which trypanosomes interact with their mammalian hosts.If you look down a microscope at the blood from a trypanosome-infected mammal, you would see these single-celled parasites, swimming amongst the red blood cells. They do not hide from the host immune defences that are designed to prevent infections. Instead they have a specialised and highly adapted cell surface mostly composed of an important protein that allows them defend themselves against attack. However, their surface is not dedicated solely to defence. They must also communicate with one another and acquire nutrients for their growth without compromising their defence which requires other protein molecules. Exactly how this is achieved is not understood fully: do they hide the other important proteins at their surface or do they have very few on the surface at any one time? I will follow the position and movements of known nutrient receptors to answer these questions as well as measure how accessible these receptors. This work will primarily be carried out at the University of Cambridge (UK) but will also involve scientists based at the University of Oxford (UK) and the University of Würzburg (Germany).Different trypanosome species interact with their mammalian hosts in different ways and in the proposed research I aim to understand the molecular basis for this. I will compare the cell surface of multiple species: the similarities tells us the important factors required for trypanosomes to infect mammals in general; the differences allows us to understand the way these species evolved and why they cause distinct disease symptoms. Most trypanosome research focusses on laboratory grown strains that are different to the trypanosomes found in cattle in Africa today. My research will compare the differences between laboratory trypanosomes and those freshly isolated from cattle in Ghana in order to reveal aspects of the trypanosome biology that are important for infectivity in mammals that would otherwise not be identified using laboratory strains. This work would be in collaboration with researchers at the University of Ghana (Ghana) and would lead to a better understanding of the infectivity of trypanosomes in mammals and how that contributes to disease.This work will begin to address long-term questions about the molecular biology and evolution of host-parasite interactions in African trypanosomes and how these affect their ability to infect and cause disease in mammals, such as humans and livestock.