恶性疟原虫是当今严重危害人类健康的疟疾病原体，其感染人体后在红细胞期可采用让以var基因为代表的各类表面抗原基因家族“相互排斥性表达”的策略，实现免疫逃避；同时，由于不同表面抗原分子与宿主细胞表面不同受体的相互黏附可在临床上导致不同的疾病表现和后果。因此，变异抗原家族的相互排斥性表达模式是其在宿主体内实现免疫逃避和致病的基础，但是其具体的调控机制尚未阐明。本研究中，我们将利用可表达全部var基因的基因敲除虫株模型，探索不同组蛋白修饰介导的染色质互作规律、反义lncRNA相关功能复合体的鉴定和转录调控机制、以及转录广谱调节因子的鉴定和作用模式，揭示var基因相互排斥性表达的调控机制；同时将通过系统生物学的方法建立var、rif和stevor等不同表面抗原基因家族表达调控的分子协作网络，并分析其互作机制，以期阐明恶性疟原虫抗原变异与致病的新机制，为恶性疟疾的防治提供新的靶点和策略。

Plasmodium falciparum is the deadliest form of human malaria, a parasitic infectious disease causing devastating consequence. After infection of human host, this parasite is able to control the antigenic variation by adopting a mutually exclusive expression strategy for those variant gene families such as var, rif and stevor, then evade human immune responses and establish a chronic infection. Thus, this gene expression mode is the basis of immune evasion and pathogenesis of this parasite, however, it still remains unclear how malaria parasites achieves this strategy in host. In this study, based upon gene knockout parasite, eg. PfSETvs, in which all the var genes were expressed, we aim to explore the regulation of chromatin interactions directed by histone modifications, the functional complex of the var gene-derived antisense lncRNAs and their related factors, and the interaction pattern of different transcriptional factors that broadly regulate expression of var genes. Meanwhile, we will establish and elucidate the molecular regulation network controlling mutually exclusive expression of the var, rif and stevor gene families using systems biology research tools. We believe these findings will contribute to understanding the mechanisms of antigenic variation and pathogenesis, and to the development of effective malaria vaccines and novel anti-malarial drugs by providing new targets for malaria prevention and treatment.