Molekulare Grundlage der Biogenese der Parasitophoren Vakuole von Plasmodium falciparum

恶性疟原虫寄生物泡生物发生的分子基础

• 批准号: 5374142
• 负责人: Professor Dr. Matthias Leippe
• 金额: --
• 依托单位: Zoologisches Institut
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2004-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5374142?language=en
• 关键词: Molekulare; Grundlage; der; Biogenese; Parasitophoren

Apicomplexa are eukaryotic unicellular organisms and obligatory intracellular parasites, the medically most relevant of which is Plasmodium falciparum. Upon invasion into human erythrocytes, Plasmodium initiates the formation of a membrane which creates a unique compartment, the parasitophorous vacuole, in which the parasite resides inside the host cell. Proteins discharged from apical secretory organelles, e.g. the rhoptries, are presumably involved in the biogenesis and maintenance of the parasitophorous vacuole membrane (PVM). Despite the pivotal role of the PVM for the parasite´s intracellular life, most of the protein components of the PVM have not been molecularly and functionally characterized. The major issue of the proposed project is the analysis of the molecular repertoire of isolated PVM by a cell-map proteomic approach using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) combined with mass spectrometry. Data from peptide mass finger prints linked to the genome project of P. falciparum will allow to identify key components of the PVM mediating functions vital for the parasite such as transport of nutrients into the vacuole and export of host cell modulating components. Kinetic studies analyzing the proteins of the PVM between plasmodial invasion into and evasion from the red blood cell, recombinant expression of selected proteins for functional studies and their immunolocalization to the synthesizing organelles will help to elucidate the biological role of the vacuolar membrane.

顶复合体是真核单细胞生物和专性细胞内寄生虫，其中医学上最相关的是恶性疟原虫。在侵入人体红细胞后，疟原虫开始形成一层膜，形成一个独特的隔室，即寄生液泡，寄生虫在宿主细胞内居住。从顶端分泌细胞器（如腺状体）排出的蛋白质可能参与寄生物液泡膜（PVM）的生物发生和维持。尽管PVM在寄生虫的细胞内生活中起着关键作用，但PVM的大多数蛋白质成分尚未被分子和功能表征。该项目的主要问题是利用二维聚丙烯酰胺凝胶电泳（2-D PAGE）结合质谱法，通过细胞图蛋白质组学方法分析分离的PVM的分子库。与恶性疟原虫基因组计划相关的肽质量指纹数据将使我们能够识别PVM介导的关键功能，如将营养物质输送到液泡和输出宿主细胞调节成分。通过动力学研究分析PVM的蛋白在疟原虫入侵和逃离红细胞之间的关系，选择蛋白进行功能研究的重组表达及其对合成细胞器的免疫定位，将有助于阐明液泡膜的生物学作用。