Newton001: Targeting the surface proteome of Trypanosoma cruzi

Newton001：针对克氏锥虫的表面蛋白质组

• 批准号: MR/M026248/1
• 负责人: Mark Field
• 金额: $ 2.7万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM026248%2F1
• 关键词: Newton001; Targeting; surface; proteome; Trypanosoma

The surface of protozoan parasites represent the interface with the host, with many roles in invasion, immune evasion, signalling, and environmental sensing. We recently identified a conserved ubiquitylation pathway in trypanosomes that controls the surface copy number of important trans-membrane domain proteins, and which provides a means for the first time to manipulate trans-membrane domain protein abundance in these parasites in a rational manor, and to assess their importance to host cell invasion and virulence. This application seeks to assess the significance of the surface protein ubiquitylation pathway in Trypanosoma cruzi for: 1. Parasite viability, host cell invasion and life cycle progression,2. Maintenance of the surface coat, specificallycopy number of trans-membrane domain proteins and their impact on the global surface proteome, 3. Possible value as a therapeutic target, by assessment of viability in vitro.The work will combine state of the art genome editing using CRISPR/Cas9 approaches, together with SILAC proteomics for unbiased analysis of the surface/cellular proteome.

原生动物寄生虫的表面是与宿主的界面，在入侵、免疫逃避、信号传递和环境感知等方面发挥着重要作用。我们最近在锥虫体内发现了一个保守的泛素化途径，它控制着重要的跨膜结构域蛋白的表面拷贝数，这为合理地控制这些寄生虫的跨膜结构域蛋白丰度提供了一种手段，并首次评估了它们对宿主细胞入侵和毒力的重要性。本应用旨在评估克氏锥虫表面蛋白泛素化途径的意义：1。2.寄主细胞侵染与寄主生命周期的关系。2 .表面涂层的维持，特别是跨膜结构域蛋白的拷贝数量及其对整体表面蛋白质组的影响。通过体外生存能力评估，作为治疗靶点的可能价值。这项工作将结合使用CRISPR/Cas9方法的最先进的基因组编辑技术，以及SILAC蛋白质组学对表面/细胞蛋白质组进行无偏分析。

项目成果

Conservation and divergence within the clathrin interactome of Trypanosoma cruzi.

克氏锥虫凝集素相互作用组的保存和分化。

• DOI: 10.1038/srep31212
• 发表时间: 2016-08-09
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Kalb LC;Frederico YC;Boehm C;Moreira CM;Soares MJ;Field MC
• 通讯作者: Field MC