Interrogating host-parasite interactomes with multiscale proteomics

用多尺度蛋白质组学研究宿主-寄生虫相互作用组

• 批准号: MR/Y010078/1
• 负责人: Oliver Crook
• 金额: $ 173.71万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY010078%2F1
• 关键词: Interrogating; host; parasite; interactomes; multiscale

Malaria is an acute disease caused by the parasite Plasmodium Falciparum, which is directly responsible for hundreds of thousands of deaths per year. Plasmodium Falciparum enters the human bloodstream when an infected mosquito penetrates the skin. The parasite then penetrates red blood cells and makes its home inside them. Here, it can hide from the human immune system whilst creating a place for it to survive. This process is often referred to as remodeling. The parasite's remarkable ability to evade the human immune system is what makes it so challenging to eradicate or design new therapeutics against it.Despite its clear importance the details of how Plasmodium Falciparum remodels the red blood cell is still unclear how it does this. We already know that the parasite uses some of the red blood cells' own proteins to carry out the necessary functions but do not have a precise understanding of which ones. It is important to understand which proteins the parasite is using so we can design drugs to stop it in its tracks.Firstly, this research will generate a "map" of interactions between the parasite and the host human cells whilst the parasite is remodeling the red blood cells for its purposes. Secondly, key interactions need to be understood in more detail and we will use other methods to see how human proteins change shape when they are used by the parasite. This will give us key insights into how they function. Finally, we will develop a new method that will allow us to examine how these interactions are changing inside the red blood cells. Together these data will provide us a new understanding of the remodeling process. In particular, it will inform medicinal chemists how to design new drugs against the malaria parasite.

疟疾是由恶性疟原虫疟原虫引起的急性疾病，该疟原虫每年直接导致数十万人死亡。当感染的蚊子穿透皮肤时，恶性疟原虫进入人体血液。然后，寄生虫穿透了红细胞，并将其家放在其中。在这里，它可以隐藏人类的免疫系统，同时为其生存而创造一个地方。这个过程通常称为重塑。寄生虫逃避人类免疫系统的非凡能力使根除或设计新的治疗剂具有挑战性的原因。尽管很重要的是，其重要性的细节是恶性疟原虫如何重塑红色血细胞仍然不清楚这是如何做到的。我们已经知道，寄生虫使用一些红细胞自己的蛋白质来执行必要的功能，但对哪些蛋白质没有精确的了解。重要的是要了解寄生虫使用哪种蛋白质，因此我们可以设计药物以在其轨道上停止它。首先，这项研究将产生寄生虫与宿主人类细胞之间相互作用的“地图”，而寄生虫则将寄生虫重塑为重塑血液细胞的目的。其次，需要更详细地了解关键相互作用，我们将使用其他方法来查看人类蛋白质在寄生虫使用时如何改变形状。这将使我们对它们的运作方式有关键的见解。最后，我们将开发一种新方法，该方法将使我们能够研究这些相互作用在红细胞内部如何变化。这些数据将共同为我们提供对重塑过程的新理解。特别是，它将告知药物化学家如何针对疟疾寄生虫设计新药。