Nutrient sensing and organelle communication in the parasites casing toxoplasmosis and malaria

弓形虫寄生虫导致婴儿和艾滋病患者死亡。疟原虫引起疟疾。这两种寄生虫在感染和传播人类期间都经历了几个阶段。所有阶段都必须侵入宿主细胞才能存活，当一个细胞中的资源耗尽时，它们必须在细胞外存活，直到找到下一个细胞。因此，在细胞外存活和在细胞内复制是这些寄生虫毒力的基本方面。与环境的错综复杂的联系使这些寄生虫能够感知营养的可用性，并决定是复制还是传播和传播。线粒体和质体是这些寄生虫的主要代谢中心，它们有独特的途径，利用从宿主细胞中清除的物质来提供不同生命阶段所需的能量和脂肪。这些功能是必不可少的，其中一些是被证实的药物靶点的来源，包括阿托瓦酮的靶标，对其耐药性的传播是不可能的。在这个项目中，我们将探索负责能量和脂肪代谢的细胞器如何相互通信，以及如何与寄生虫内的其他细胞器通信，以响应养分供应的变化和决定细胞命运。我们将重点介绍葡萄糖和脂肪的感知途径，以及线粒体和质体之间的分子交换。为此，我们将结合反向遗传学、药物筛选、代谢组学和体外弓形虫和疟原虫成像方法。

Toxoplasma parasites cause death of babies and AIDS patients. Plasmodium spp, causes malaria. Both parasites go through several stages during their infection and dissemination of a human. All stages must invade cells of their host to survive and when resources run out in one cell they must survive extracellularly until they find the next cell. Surviving extracellularly and replicating intracellularly are thus essential aspects of these parasite's virulence. Intricate connection with the environment allows these parasites to sense nutrient availability and to decide whether to replicate or to disseminate and transmit. Mitochondria and plastids are the main metabolic centres in these parasites and they have unique pathways that utilized scavenged materials from the host cell to provide the energy and lipid needed in the various life stages. These functions are essential and some of them are confirmed sources for drug targets, including the target of Atovaquone, for which the spread of drug resistance is unlikely.In this project we will explore how the organelles responsible for energy and lipid metabolism communicate with each other and with other organelles within the parasite to respond to change in nutrient availability and to determines cell fate. We will focus on glucose and lipid sensing pathways and on exchange of molecules between mitochondrion and plastid. For this we will combine reverse genetics, drug screening, metabolomics and imaging approaches in vitro in Toxoplasma and in Plasmodium.