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

微小隐孢子虫是非洲腹泻和营养不良的主要病原体之一，目前还没有疫苗可用，FDA批准的唯一药物硝唑尼特对免疫功能低下的人无效，因此迫切需要新药。这个PHD项目旨在鉴定和验证一种化合物的作用机制和药物靶点，该化合物已被鉴定为在微小隐孢子虫的高通量筛选中的热门化合物。为了实现这一点，我将首先测定化合物的宿主细胞毒性，以验证HIT是由于微小弧菌的死亡所致，并使用热蛋白质组谱(TPP)等方法分别鉴定化合物的靶标。随后，将对药物靶点进行基因验证，以确保假设的靶点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，可以用更优化的药物来开发。

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.