由疟原虫导致的疟疾是当前人类三大传染病之一，也是人类疾病防治领域的一大难题。恶性疟原虫可以成功地在人体内实现免疫逃逸，其关键机制是疟原虫表面抗原var基因家族内60个基因成员之间的相互排斥性表达策略。目前，调节var基因家族转录的关键性转录因子及其作用机制尚不清楚。在申请人前期研究中，已首次鉴定到一个var基因家族广谱转录因子PfAP2-V，为探索其参与调节var基因相互排斥性表达的分子机制，本项目拟开展如下研究：1）鉴定PfAP2-V调节不同var基因转录的作用方式及分子机制，筛选可同时、高效表达全部var基因产物PfEMP1的双基因编辑恶性疟原虫克隆；2）鉴定与PfAP2-V共调控var基因转录的其他关键调控因子的生化活性，及其作用的分子机制。本研究对揭示恶性疟原虫规避人体免疫反应的调控机制具有重要意义，也将为疟疾疫苗研制提供实验依据。

Malaria caused by Plasmodium parasites is count for one of the three major human infectious diseases in the world, and becomes also a major problem in the field of human disease prevention and control. Plasmodium falciparum can successfully escape the attack of human immune system, the key mechanism is the mutually exclusive expression strategy of the var gene family, in which each of 60 members encode a surface antigen called PfEMP1. At present, the key transcription factors and the regulation mechanism of var gene family is not clear. In our unpublished study, a transcription factor PfAP2-V that can control expression of all var genes was identified for the first time. To explore its molecular mechanism in var gene regulation, the following studies will be carried out: 1). Identify the mechanism of PfAP2-V in regulating the transcription of var genes, and to isolate the transgenic parasite clones containing PfSET2 knockout and PfAP2-V overexpression, which can simultaneously and highly express all the var gene product PfEMP1. 2).Identify the biochemical activity of the key transcription factor and its molecular mechanism, related to PfAP2-V. This study will improve the understanding of immune evasion in Plasmodium faciparum, and will also benefit the development of malaria vaccines.