Investigation of conserved proteins that regulate transmission of the malaria parasite and Toxoplasma gondii.

研究调节疟疾寄生虫和弓形虫传播的保守蛋白。

• 批准号: 2885569
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2885569
• 关键词: Investigation; conserved; proteins; regulate; transmission

The malaria parasite, Plasmodium, and Toxoplasma gondii are related protozoal parasites that infect ~1/2 of the global population and cause a massive burden of death and disease. Although they have evolved very different mechanisms to undergo transmission between their hosts, there may be conserved features in the molecular mechanism that regulate the development of the T. gondii cysts, that survive ingestion and passage through the gastro-intestinal tract, and the development of malaria parasite oocysts in the mosquito midgut. This project will investigate the role of conserved proteins that are essential for the development of these transmission forms, with the aim of identifying new targets of therapeutics that disrupt the parasite lifecycles. We have previously identified a family of large surface proteins, the Cysteine Repeat Modular Proteins (CRMPs), that are essential for Plasmodium sporozoite development and egress from the oocyst. This project will investigate the role of CRMPs in the experimentally-amenable T .gondii model during cyst development in vitro and during chronic infection in vivo. In parallel, high-throughput CRISPR genetic screens will be carried out in T. gondii cysts cultured in vitro to identify novel proteins which are essential for cyst development and parasite differentiation and egress. Candidate genes will be disrupted in Plasmodium and Toxoplasma and differentiation and cyst formation will be assessed using high-resolution microscopy, biochemical approaches and infection assays.

疟疾寄生虫、疟原虫和刚地弓形虫是相关的原生动物寄生虫，感染了全球约1/2的人口，造成了巨大的死亡和疾病负担。虽然它们在宿主之间的传播机制进化得非常不同，但在调节弓形虫囊发育的分子机制中可能存在一些保守的特征，弓形虫囊在摄入并通过胃肠道后存活，以及疟原虫卵囊在蚊子中肠中的发育。该项目将研究保守蛋白的作用，这些蛋白对这些传播形式的发展至关重要，目的是确定破坏寄生虫生命周期的治疗新靶点。我们之前已经确定了一个大的表面蛋白家族，半胱氨酸重复模块蛋白（CRMPs），这是疟原虫孢子发育和从卵囊出口所必需的。本项目将研究crmp在实验可接受的T。弓形虫模型在体外囊肿发育和体内慢性感染过程中的作用。与此同时，高通量CRISPR基因筛选将在体外培养的弓形虫囊中进行，以鉴定对囊发育和寄生虫分化和出口至关重要的新蛋白。候选基因将在疟原虫和弓形虫中被破坏，分化和囊肿形成将使用高分辨率显微镜、生化方法和感染分析进行评估。