Functional analysis of molecular components of the habitat of Leishmania spp. - the protozoan parasites causing human leishmaniases

利什曼原虫栖息地分子成分的功能分析。

• 批准号: 198126033
• 负责人: Dr. Anton Aebischer
• 金额: --
• 依托单位: Fachgebiet 16: Erreger von Pilz- und Parasiteninfektionen und Mykobakteriosen
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/198126033?language=en
• 关键词: Functional; analysis; molecular; components; habitat

Leishmania spp. are medically important intracellular proteozoan parasites. Using a proteomics approach we have previously comprehensively analysed parasite adaptation to its intracellular habitat in macrophages. Here we propose to extend and complement this approach by analysing the host cell-derived membrane and soluble proteins that contribute to this habitat. Specifically we propose to perform a comparative in silico analysis of host phagosomal multiprotein complexes between Leishmania- and latex bead-containing phagosomes to define functionally relevant differences. . Furthermore, we will pursue the relevance of one already identified difference and test the hypothesis that i) Cholesterol/lipid accumulation in Leishmania-PVs, ii) up-regulation of host cell cholesterol synthesis pathways, iii) inhibition of membrane raft dependent signalling cascades and iv) up-regulation of fatty acid catabolism in parasites are mechanistically linked and interdependent. Finally, we simultaneously want to establish experimental platforms based on ES cell- and transgenic mouse-derived primary phagocytic cells that will allow to harness the power of reverse genetics or RNAi to analyse phagosomal protein function in different cell contexts.

利什曼是医学上重要的细胞内蛋白虫寄生虫。使用蛋白质组学方法，我们以前全面分析了寄生虫适应其细胞内栖息地的巨噬细胞。在这里，我们建议通过分析宿主细胞衍生的膜和可溶性蛋白，有助于这个栖息地扩展和补充这种方法。具体来说，我们建议进行比较在电脑分析宿主吞噬体多蛋白复合物之间的利什曼原虫和乳胶珠含吞噬体，以定义功能相关的差异。.此外，我们将继续研究一个已经确定的差异的相关性，并检验以下假设：i）利什曼原虫-PV中的胆固醇/脂质蓄积，ii）宿主细胞胆固醇合成途径的上调，iii）膜筏依赖性信号级联的抑制和iv）寄生虫中脂肪酸催化剂的上调是机械联系和相互依赖的。最后，我们同时希望建立基于ES细胞和转基因小鼠衍生的原代吞噬细胞的实验平台，这将允许利用反向遗传学或RNAi的力量来分析不同细胞环境中的吞噬体蛋白功能。