A comparative proteomic approach to identify and validate African trypanosome proteins at the host-parasite interface

一种比较蛋白质组学方法来识别和验证宿主-寄生虫界面的非洲锥虫蛋白

• 批准号: G0900255/1
• 负责人: Mark Field
• 金额: $ 41.28万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0900255%2F1
• 关键词: comparative; proteomic; approach; identify; validate

Parasitic diseases afflict many of the world?s population, and the majority of people on our planet at at risk from one or several such agents. The diseases these parasites cause range from malaria to gut, skin and organ infections. In Africa, the trypanosome parasite is responsible for much death and morbidity - infection is brought about when an infected tsetse fly takes a blood meal. Without treatment the infected person will progress through general ill health symptoms to multiple organ malfunction, coma and death. Related trypanosomes also cause disease in Asia, South America, the Middle East and Southern Europe.Due to a remarkable system where the African trypanosome changes its coat at regular intervals, the host immune system is unable to control the parasite, which results in efficient infection and invariably death if untreated. Vaccines are unlikely due to the varying coat, and the drugs in use at over 50 years old, frequently toxic and failing due to emergence of resistance. Urgent new research is needed to identify potential new therapeutic options and diagnostics. One aspect of the parasite that is unique is a region of the surface where all molecules that form the coat emerge when they are made, called the flagellar pocket. As the surface is the boundary between host and parasite, understanding how this is maintained is of major scientific interest as well as of practical utility in uncovering new ways in which the trypanosome may be vulnerable to drug treatments. We wish to find out what proteins are present in the flagellar pocket, with the expectation that an understanding of the molecules that are present will provide insights into how the pocket performs its job. There has so far been limited success with defining the flagellar pocket, and we propose a method that requires considerable computer power and wide-raging analysis as a solution to the problem. Most importantly, following on from the identification of candidate flagellar pocket proteins, we will look to see which expected proteins have been identified, and also, in combination with computer predictions, will localize a range of unknown proteins using the jellyfish green fluorescent protein, or GFP. This will allow us to assess how many of the proteins really are parts of the flagellar pocket, and hence begin to understand how this organelle contributes to the ability of the trypanosome to cause disease.

寄生虫病困扰着世界上许多国家？的人口，以及我们这个星球上的大多数人都面临着一个或几个这样的代理人的风险。这些寄生虫引起的疾病范围从疟疾到肠道，皮肤和器官感染。在非洲，锥虫寄生虫是造成许多死亡和发病的原因-感染是当受感染的采采蝇吸食血液时引起的。如果不进行治疗，受感染者将从一般的健康不良症状发展到多器官功能障碍、昏迷和死亡。相关的锥虫也会在亚洲、南美洲、中东和南欧引起疾病。由于非洲锥虫有一个显着的系统，即每隔一段时间就改变其外壳，宿主的免疫系统无法控制寄生虫，这导致有效的感染，如果不治疗，总是会死亡。疫苗是不太可能的，由于不同的外套，并在使用的药物在50岁以上，经常有毒和失败，由于出现耐药性。迫切需要进行新的研究，以确定潜在的新的治疗选择和诊断。这种寄生虫的一个独特之处是表面的一个区域，当它们形成时，形成外壳的所有分子都会出现，称为鞭毛口袋。由于表面是宿主和寄生虫之间的边界，了解这是如何维持的是主要的科学兴趣，以及在发现锥虫可能易受药物治疗的新方式方面的实际效用。我们希望找出鞭毛口袋中存在哪些蛋白质，期望对存在的分子的理解将提供口袋如何执行其工作的见解。到目前为止，定义鞭毛口袋的成功是有限的，我们提出了一种方法，需要相当大的计算机能力和广泛的愤怒的分析作为解决问题的方法。最重要的是，从候选鞭毛口袋蛋白的识别，我们将期待看到哪些预期的蛋白质已被确定，并结合计算机预测，将本地化一系列未知的蛋白质使用水母绿色荧光蛋白，或GFP。这将使我们能够评估有多少蛋白质真正是鞭毛口袋的一部分，从而开始了解这种细胞器如何有助于锥虫致病的能力。