Unravelling the function of protein phosphatases in malaria parasite biology .

疟疾是一种传染病，每年导致5亿人临床患病，100万人死亡，主要是儿童。引起这种疾病的单细胞寄生虫通过受感染蚊子的叮咬传播，它首先在肝脏中发育和繁殖，然后被释放到血液中，在那里它感染并在红细胞中繁殖。这种血液阶段导致临床症状，包括高烧，在某些情况下导致死亡。为了使寄生虫从一个人传播到另一个人，它也感染蚊子。寄生虫在蚊子（肠道和唾液腺）和人类宿主（肝脏和红细胞）的不同组织中经历复杂的发育阶段。调节这些过程的信号还没有得到正确的理解，但来自其他生物体的研究已经确定了酶家族，蛋白磷酸酶和蛋白激酶对这些变化很重要。疟原虫的基因组包含大约30个蛋白磷酸酶基因。最近在分析疟疾基因功能方面取得的进展使我们有可能通过破坏每个基因并观察其后果来研究这些分子的功能。我们可以看到，如果这些蛋白质不再被制造，或者如果它们被标记上荧光标记，我们可以在显微镜下看到它们在寄生虫中的位置。在本项目中，缺乏这些磷酸酶的寄生虫将在哺乳动物和昆虫宿主的整个生命周期中被制造和分析。一些在血液阶段必不可少的蛋白质，我们将无法破坏。这种功能性筛选将提供一种强大而独特的方法，根据对疟疾寄生虫基本发育生物学的了解，优先考虑抗疟疾新药的目标。

Malaria is an infectious disease that causes clinical disease in 500 million humans and results in 1million deaths mainly in children each year. The single cell parasite causing the disease is transmitted by the bite of an infected mosquito and it develops and multiplies first in the liver and then is released into the blood stream, where it infects and multiplies in red blood cells. This blood stage results in the clinical symptoms including high fever and in some cases causes death. In order for the parasite to be transmitted from one person to another it also infects mosquitoes. Parasites undergo complex developmental stages in the different tissues of the mosquito (gut and salivary gland) and the human host (liver and red blood cells). The signals which regulate these processes are not properly understood but studies from other organisms have identified families of enzymes, the protein phosphatases and protein kinases important for such changes. The genome of the malaria parasite contains about 30 genes for protein phosphatases. Recent advances in analysing the function of genes in malaria now allow us the possibility to study the function of these molecules by disrupting each of the genes and observing the consequences. We can see what happens if the proteins in question are no longer made, or if they are tagged with a fluorescent marker we can see where they are located in the parasite under the microscope.In the present project, parasites lacking these phosphatases will be made and analysed throughout the complete life cycle in both mammalian and insect hosts. Some of the proteins that are essential in the blood stage we will be unable to disrupt. This functional screen will provide a powerful and unique way to prioritise the targets for new drugs against malaria based on understanding the fundamental developmental biology of malaria parasite.