Glycosome biogenesis in African trypanosomes

项目摘要/摘要 糖体是在动质体内发现的重要的、寄生虫特有的细胞器，是 影响全球7000多万人的疾病。目前，在这方面存在一个根本性的差距 了解调节糖体生物学的机制。长期目标是确定 动质体内糖体的维持、生物发生和重塑的机制 布氏锥虫。中心假说是糖体通过形成前糖体形成从头开始形成。 通过蛋白质输入的一系列过程成熟的糖体小泡，并预测糖体 蛋白质含量在成熟过程中会发生变化，并对环境条件做出反应。这个 这项提议的短期目标是描述影响糖体成熟的分子机制。 和改建。这个项目的基本原理是了解调节糖体的机制 生物学将揭示诱人的新药靶点。为实现这些目标，我们将开展以下具体工作 目的：1)确定糖体蛋白TbPEX11在不同糖体中的翻译后修饰 群体，2)确定调节糖体重塑的途径，以响应 环境条件3)确定糖体蛋白表达的葡萄糖依赖变化和 转录组对胞外葡萄糖的反应。这项工作意义重大，将对该领域产生积极影响，因为 它将解析糖体生物发生的机制，并阐明可利用的过程 治疗性设计。

PROJECT SUMMARY/ABSTRACT Glycosomes are essential, parasite-specific organelles found in kinetoplastids, the causative agents of diseases affecting more than 70 million people globally. Currently, there is a fundamental gap in the knowledge of the mechanisms that regulate glycosome biology. The long-term goal is to identify the mechanisms involved in the maintenance, biogenesis and remodeling of glycosomes in the kinetoplastid Trypanosoma brucei. The central hypothesis is that glycosomes form de novo through the formation of pre- glycosomal vesicles that mature through a sequential process of protein import and predict that glycosome protein content changes during the maturation process and in response to environmental conditions. The short-term goal of this proposal is to characterize the molecular mechanisms that affect glycosome maturation and remodeling. The rationale for this project is that understanding the mechanisms that regulate glycosome biology will reveal attractive new drug targets. In pursuit of these goals, we will carry out the following specific aims: 1) Identify the post-translational modifications of the glycosome protein, TbPEX11, in different glycosome populations, 2) Identify the pathways that regulate glycosome remodeling in response to changes in environmental conditions 3) Identify glucose-dependent changes in glycosome protein expression and transcriptome response to extracellular glucose. This work is significant and will positively impact the field, as it will resolve mechanisms of glycosome biogenesis and elucidate processes that can be exploited for therapeutic design.