Mechanisms by which African trypanosomes sense and respond to iron availability in the mammalian host

生物体有能力感知其环境的变化，并调整其基因表达以确保其生存。从环境中获取营养对单细胞生物尤其重要，尤其是单细胞寄生虫，它们必须从宿主那里获取营养。铁是所有生命形式生长的必需元素，哺乳动物通过将铁与一种称为转铁蛋白的蛋白质结合来严格控制铁的可用性，以防止入侵生物的生长。非洲锥虫是一种单细胞寄生虫，在撒哈拉以南非洲通过受感染的采采蝇叮咬传播，并在农场动物和人类中引起疾病。该寄生虫能够通过表达一种识别并从其宿主摄取转铁蛋白的蛋白质来满足其对铁的需求，重要的是能够快速增加这种蛋白质的量以响应铁饥饿。寄生虫能够做到这一点的方式尚不清楚，但我们确实知道它与哺乳动物使用的机制不同。该项目将研究寄生虫能够感知和响应铁饥饿的方式，使用在烧瓶中生长的寄生虫细胞的实验技术相结合。研究这种机制很重要，因为它将帮助我们了解这些寄生虫如何感知和适应宿主环境，这些知识将有助于对抗它们引起的疾病。改善对这些机制的基本理解对于我们理解发生失调的代谢疾病和癌症也很重要。

Living organisms have the ability to sense changes in their environment and adapt their gene expression to ensure their survival. The acquisition of nutrients from their environment is particularly important for unicellular organisms, especially for unicellular parasites that must acquire nutrients from their host. Iron is an essential element for the growth of all forms of life, and mammals tightly control the availability of iron to prevent the growth of invasive organisms by binding iron to a protein called transferrin. The African trypanosomes are unicellular parasites that are transmitted by the bite of an infected tsetse fly in sub-Saharan Africa, and causes a disease in farm animals and humans. The parasite is able to fulfil its requirement for iron by expressing a protein that recognises and uptakes transferrin from its host, and importantly is able to rapidly increase the amount of this protein in response to iron starvation. The way the parasite is able to do this is not clear, but we do know that it is different to the mechanism used by mammals. This project will investigate the way in which the parasite is able to sense and respond to iron starvation using a combination of experimental techniques that use parasite cells grown in flasks. Studying this mechanism is important as it will help us to understand how these parasites sense and adapt to their host environments, knowledge that will help in the fight against the diseases they cause. Improved fundamental understanding of these mechanisms is also important for our understanding of metabolic diseases and cancers where disregulation occurs.