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的过程中都会经历几个阶段。所有阶段都必须侵入宿主细胞才能生存，当一个细胞的资源耗尽时，它们必须在细胞外生存，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重要方面。与环境的复杂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，它们具有独特的途径，利用从宿主细胞清除的物质来提供各个生命阶段所需的能量和脂质。这些功能是必不可少的，其中一些是药物靶点的确认来源，包括阿托伐醌的靶点，对它的耐药性的传播是不太可能的。在这个项目中，我们将探讨负责能量和脂质代谢的细胞器如何相互通信，并与寄生虫内的其他细胞器，以响应营养物质的变化，并决定细胞的命运。我们将集中在葡萄糖和脂质的传感途径，并在分子之间的交换，叶绿体和质体。为此，我们将结合联合收割机反向遗传学，药物筛选，代谢组学和成像方法在体外弓形虫和疟原虫。

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.