Understanding inter-organellar communication in apicomplexan parasites

项目摘要/摘要 细胞器间的通讯是细胞功能所必需的过程。在细胞内，细胞器可以 通过称为膜接触位点(MCSs)的特殊微域相互作用。这些结构调解了 两个细胞器膜紧密对接，允许代谢物交换。在这样做的过程中，MCS 对细胞动态平衡和代谢可塑性至关重要。然而，人们对MCS的大多数了解都来自于 仅来自少数经过充分研究的后生动物，特别是酵母和哺乳动物。研究其功能和功能 其他真核生物中MCSs的组成--特别是在具有门特有的不同谱系中 细胞器--因此，对于深入了解需要独立解决相互关系的机制至关重要。 细胞器交流。 我的小组试图了解细胞器间的通讯在顶端复合体中，是一群寄生的原生生物 这包括疟疾和弓形虫病的病原体。在它们复杂的生命周期中，其中许多 当生物体进入和离开不同宿主物种的细胞时，它们会在各种环境中过渡。这个 在多种细胞类型中繁殖的能力取决于从不同类型的细胞中获取营养的能力 不断变化的环境，这突出了顶端复合体的代谢可塑性。大多数尖端复合体 拥有一个线粒体和一个质外体，即一种非光合体，它起源于一个次生体 至少在6亿年前发生了一次内共生事件。从那以后，这两个细胞器一直在共同进化，现在 在这些寄生虫的代谢可塑性和生存中起着至关重要的作用。尽管亲密的身体互动 在线粒体和顶生质体之间已经观察到这种相互作用的分子同一性 仍然难以捉摸。 利用弓形虫顶端复合体模型，我的实验室旨在识别分子效应器 使用两种不同但互补的方法来调节线粒体-顶体相互作用： 邻近生物素化和双分子互补。因为顶生质体是顶端复合体特有的 细胞器，鉴定参与线粒体-质外体MCSs的蛋白质可以提供机会 用于设计针对这些病原体的抗寄生虫疗法。我们的工作将开辟新的科学场所 顶端复合体生物学，并对这些生物的进化和细胞器串扰有深入的了解。

PROJECT SUMMARY/ABSTRACT Inter-organellar communication is an essential process for cellular function. Inside the cell, organelles can interact through specialized microdomains called membrane contact sites (MCSs). These structures mediate the close apposition of two organellar membranes, allowing the exchange of metabolites. In doing so, MCSs are crucial for cellular homeostasis and metabolic plasticity. However, most of what is known about MCSs comes only from a handful of well-studied metazoans, particularly yeast and mammals. Studying the function and composition of MCSs in other eukaryotes—particularly in divergent lineages possessing phylum-specific organelles—is therefore crucial to gain insights into the mechanisms requiring an independent solution to inter- organellar communication. My group seeks to understand inter-organellar communication in apicomplexans, are a group of parasitic protists that include the causative agents of malaria and toxoplasmosis. In their complex life cycles, many of these organisms transition through a variety of environments as they enter and exit cells in different host species. The ability to propagate within a wide range of cell types relies on the capacity to access nutrients from diverse and changing environments, which underscores the metabolic plasticity of apicomplexans. Most apicomplexans possess a single mitochondrion and an apicoplast, a non-photosynthetic plastid that arose from a secondary endosymbiotic event at least 600 million years ago. Both organelles have been coevolving ever since, and now play crucial roles in the metabolic plasticity and survival of these parasites. Although a close physical interaction between the mitochondrion and the apicoplast has been observed, the molecular identity of this interaction remains elusive. Using the model apicomplexan Toxoplasma gondii, my laboratory aims to identify the molecular effectors mediating the mitochondrion-apicoplast interaction using two different, yet complementary approaches: proximity biotinylation and bimolecular complementation. As the apicoplast is an apicomplexan-specific organelle, the identification of proteins involved in mitochondrion-apicoplast MCSs could provide opportunities for the design of anti-parasitic therapies against these pathogens. Our work will open new scientific venues of apicomplexan biology, and yield insight into the evolution and organellar crosstalk in these organisms.