Functional analysis of GRASP in protein transport and Golgi architechture in the malaria parasite Plasmodium falciparum

疟原虫恶性疟原虫蛋白质运输和高尔基体结构中 GRASP 的功能分析

• 批准号: 401956-2011
• 负责人: Gilberger, Tim
• 金额: $ 2.91万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=515530
• 关键词: Functional; analysis; GRASP; protein; transport

All known eukaryotic cells developed specialized compartments within themselves to provide designated reaction chambers in order to control their metabolism. These cells mastered this challenge by evolving a complex endomembrane system. This re-design came with an additional expense: They had to make sure that there is a system in place that is mediating the communication between the individual, subcellular divisions. Within this system, the Golgi apparatus is the operational centerpiece. Although the polarity of this organelle with its cis and trans face is universally conserved, the morphology of the Golgi varies greatly throughout the eukaryotic phylogenetic tree. In this research program we will explore the Golgi of the malaria parasite. This intracellular pathogen with a devastating impact on mankind developed a unique transport system to conquer its ecological niche: the human hepatocytes and erythrocytes. We will exploit the "simple" Golgi morphology of the parasite and its specialized mechanism of protein transport to address some fundamental questions about organelle biology and protein transport. To do so we will focus on the functional analysis of GRASP - a protein that it is involved Golgi architecture and protein trafficking. We will not only probe deep into some elementary questions of cell biology but also initiate translational applications to exploit protein trafficking as a therapeutical target.

所有已知的真核细胞都在自身内部形成了专门的隔室，以提供指定的反应室，从而控制它们的代谢。这些细胞通过进化出复杂的内膜系统来应对这一挑战。这种重新设计带来了额外的费用：他们必须确保有一个系统在调解个体亚细胞分裂之间的通信。在这个系统中，高尔基体是运作的中心。虽然这个细胞器的极性与其顺式和反式的脸是普遍保守的，高尔基体的形态变化很大，在整个真核生物系统发育树。在这个研究项目中，我们将探索疟原虫的高尔基体。这种对人类具有毁灭性影响的细胞内病原体开发了一种独特的运输系统来征服其生态位：人类肝细胞和红细胞。我们将利用寄生虫的“简单”高尔基体形态及其蛋白质转运的特殊机制来解决有关细胞器生物学和蛋白质转运的一些基本问题。为此，我们将重点分析GRASP的功能-一种蛋白质，它涉及高尔基体的结构和蛋白质运输。我们不仅将深入探讨细胞生物学的一些基本问题，而且还将启动翻译应用，以利用蛋白质运输作为治疗靶点。