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

非洲锥虫是一种单细胞寄生虫，生活在撒哈拉以南非洲的哺乳动物的血液中，通过采采蝇的叮咬在哺乳动物之间传播。几种锥虫导致牛和其他牲畜患病，导致农民生产力损失。这种疾病是受影响地区的巨大经济负担，导致非洲农村家庭的生活机会减少。其中一种锥虫能够感染人类并导致致命疾病。目前的药物治疗是低效和有毒的。寄生虫从宿主那里获得营养，避免被宿主免疫系统杀死，并适应它们可以感染的不同哺乳动物。通过我的研究，我最终想了解并干预锥虫与哺乳动物宿主相互作用的方式。如果你在显微镜下观察感染锥虫的哺乳动物的血液，你会看到这些单细胞寄生虫，在红细胞中游动。它们不会躲避宿主旨在预防感染的免疫防御。相反，它们有一个专门的和高度适应的细胞表面，主要由一种重要的蛋白质组成，使它们能够抵御攻击。然而，它们的表面并不仅仅用于防御。它们还必须相互交流，并在不损害其防御的情况下获得生长所需的营养，而防御需要其他蛋白质分子。究竟是如何实现这一点还不完全清楚：它们是将其他重要的蛋白质隐藏在表面，还是在任何时候都只有很少的蛋白质在表面？我将跟踪已知营养受体的位置和运动来回答这些问题，并测量这些受体的可达性。这项工作将主要在剑桥大学（英国）进行，但也将涉及牛津大学（英国）和维尔茨堡大学（德国）的科学家。不同的锥虫物种以不同的方式与哺乳动物宿主相互作用，在拟议的研究中，我的目标是了解这种相互作用的分子基础。我将比较多个物种的细胞表面：相似之处告诉我们锥虫感染哺乳动物所需的重要因素;差异使我们能够了解这些物种的进化方式以及为什么它们会引起不同的疾病症状。大多数锥虫研究集中在实验室培养的菌株，与今天在非洲牛中发现的锥虫不同。我的研究将比较实验室锥虫和那些新鲜分离的牛在加纳之间的差异，以揭示锥虫生物学的方面是重要的哺乳动物的感染性，否则将无法使用实验室菌株确定。这项工作将与加纳大学（加纳）的研究人员合作进行，并将导致更好地了解锥虫在哺乳动物中的感染性及其如何促成疾病，这项工作将开始，以解决非洲锥虫中宿主-寄生虫相互作用的分子生物学和进化以及这些相互作用如何影响其感染哺乳动物和引起疾病的能力等长期问题。例如人类和牲畜。

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.