Understanding inter-organellar communication in apicomplexan parasites

了解顶复门寄生虫的细胞器间通讯

• 批准号: 10714402
• 负责人: Diego Huet
• 金额: $ 37.75万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-22 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714402
• 关键词: Antiparasitic Agents; Biology; Biotinylation; Cell physiology; Cells; Communication; Complement; Complex; Development; Environment; Eukaryota; Event; Evolution; Homeostasis; Knowledge; Laboratories; Life Cycle Stages; Malaria; Mammals; Mediating; Membrane; Metabolic; Modeling; Molecular; Nutrient; Organelles; Organism; Parasites; Pathogenicity; Plastids; Play; Proteins; Research; Role; Site; Structure; Toxoplasma gondii; Toxoplasmosis; Work; Yeasts; cell type; design; human disease; insight; pathogen; protein structure

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.

项目总结/摘要 细胞器间通讯是细胞功能的重要过程。在细胞内，细胞器可以 它们通过称为膜接触位点（MCSs）的特殊微区相互作用。这些结构介导 两个细胞器膜的紧密并置，允许代谢物的交换。在此过程中，MCS 对细胞内稳态和代谢可塑性至关重要。然而，大多数关于MCS的知识来自于 只有少数经过充分研究的后生动物，特别是酵母和哺乳动物。学习函数和 在其他真核生物中，特别是在具有门特异性的不同谱系中， 因此，至关重要的是要深入了解机制，需要一个独立的解决方案， 细胞器通讯 我的小组试图了解顶复门中的细胞器间通讯，顶复门是一组寄生原生生物 包括疟疾和弓形虫病的病原体。在它们复杂的生命周期中， 当生物体进入和离开不同宿主物种的细胞时，它们在各种环境中过渡。的 在广泛的细胞类型内繁殖的能力依赖于从不同的细胞类型获得营养的能力， 不断变化的环境，这强调了顶复门的代谢可塑性。大多数顶复门 具有一个单胞体和一个顶质体，顶质体是一种非光合作用的质体，由次生 至少6亿年前的内共生事件从那以后，这两种细胞器就一直在共同进化， 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。虽然亲密的身体接触 之间的相互作用已经观察到，这种相互作用的分子身份 仍然难以捉摸 本实验室以顶复虫弓形虫为模型， 使用两种不同但互补的方法介导顶质体-顶质体相互作用： 邻近生物素化和双分子互补。由于顶质体是顶复体特有的 细胞器，鉴定参与细胞器-顶质体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， apicomplexan生物学，并深入了解这些生物体的进化和细胞器串扰。