Identification of essential host cell factors for the survival of the obligate intracellular apicomplexan parasite Toxoplasma gondii

鉴定专性细胞内顶复门寄生虫弓形虫生存所必需的宿主细胞因子

• 批准号: 29202105
• 负责人: Professor Dr. Michael Boutros
• 金额: --
• 依托单位: Experimentelle Parasitologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/29202105?language=en
• 关键词: Identification; essential; host; cell; factors

The phylum Apicomplexa is composed of over five thousand parasitic species, which cause several diseases in humans and animals. These parasites are obligate intracellular and highly dependent on host cell factors. Whereas invasion of the host cell occurs in an active process independently of host cell phagozytosis that involves the parasites ability to glide, the intracellular survival of the parasite highly depends on host cell metabolism and the ability of the parasite to interfere, modulate and use signaling cascades of the host cells for its own purpose. While knowledge of essential parasite proteins involved in these mechanisms is increasing current understanding of the specific interaction partners and host cell factors contributing to pathogenesis is still in its infancy. The purpose of this proposal is to perform a genome wide RNAi screen on HeLa cells that will serve as host cells for Toxoplasma gondii in order to identify essential factors derived from the host cell, needed for invasion, intracellular replication and egress. Therefore RNAi-treated HeLa cells will be infected with T.gondii and propagation of the parasite will be followed over time. We aim to identify factors that are essential for successful propagation of the parasite whereas host cell viability itself is not affected. This will not only broaden our knowledge on host-parasite interactions but might also lead to the identification of new drug candidates against apicomplexan parasites.

顶复合体门由五千多种寄生虫组成，它们会导致人类和动物的几种疾病。这些寄生虫是专性的细胞内和高度依赖于宿主细胞因子。尽管寄生虫对宿主细胞的入侵发生在一个独立于宿主细胞吞噬的活跃过程中，涉及到寄生虫的滑翔能力，但寄生虫的细胞内存活高度依赖于宿主细胞的代谢和寄生虫干预、调节和利用宿主细胞信号级联的能力。虽然对参与这些机制的必需寄生虫蛋白的了解正在增加，但目前对参与发病机制的特定相互作用伙伴和宿主细胞因子的了解仍处于起步阶段。本提案的目的是对作为刚地弓形虫宿主细胞的HeLa细胞进行全基因组范围的RNAi筛选，以鉴定源自宿主细胞的入侵、细胞内复制和退出所需的关键因子。因此，经过rnai处理的HeLa细胞将被弓形虫感染，并且随着时间的推移，寄生虫的繁殖将被跟踪。我们的目标是确定对寄生虫成功繁殖至关重要的因素，而宿主细胞活力本身不受影响。这不仅将扩大我们对宿主-寄生虫相互作用的认识，而且可能导致鉴定新的抗顶复合体寄生虫候选药物。