Target Identification of anti-cryptosporidials compounds from High throughput screenings against Cryptosporidium parvum

通过针对小隐孢子虫的高通量筛选来鉴定抗隐孢子虫化合物

• 批准号: 2609156
• 金额: --
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2609156
• 关键词: Target; Identification; anti; cryptosporidials; compounds

Cryptosporidium parvum is one of the top causative agents of diarrheal disease and malnutrition in Africa with no vaccine available and the only FDA approved drug Nitazoxanide is ineffective in immunocompromised individuals, so the need for new drugs is sorely needed. This PhD project aims to identify and validate the mechanism of action and drug target of a compound that has been identified as a hit from high throughput screens in C. parvum. To achieve this, I will first determine the compounds host cell toxicity to validate that the hit is due to C. parvum death and use methods such as thermal proteomic profiling (TPP) to identify the compounds target respectively. Following this, genetic validation of the drugs target will be performed ensuring that the hypothetical target is essential for parasite survival. The success of this project would identify a new drug target that can be exploited with more optimised drugs.

隐孢子虫是非洲疟疾和营养不良的主要病原体之一，没有可用的疫苗，并且唯一FDA批准的药物Nitazoxanide对免疫功能低下的个体无效，因此迫切需要新药。该博士项目旨在确定和验证一种化合物的作用机制和药物靶点，该化合物已被确定为C中高通量筛选的热门化合物。小的为了实现这一点，我将首先确定化合物的宿主细胞毒性，以验证命中是由于C。并使用诸如热蛋白质组学分析（TPP）的方法来分别鉴定化合物靶标。在此之后，将对药物靶标进行遗传验证，以确保假设的靶标对寄生虫的生存至关重要。该项目的成功将确定一个新的药物靶点，可以利用更优化的药物。