由按蚊传播的疟疾是全球公共卫生的重大威胁，每年近百万死亡病例主要由恶性疟原虫感染引起。疟原虫的生长繁殖、感染宿主、致病等过程皆依赖于精密而复杂的基因表达调控机制，其中最具代表性的是多拷贝变异基因家族的排他性表达模式，主要依赖于表观遗传学调控途径，但是迄今仍然未能完全解释疟原虫抗原变异的分子机制。在本课题中，我们拟从一个崭新的角度探索恶性疟原虫基因表达调控机制，即在高分辨率的疟原虫染色体构象捕获基础上，结合全基因组水平上的染色质修饰图谱和动态转录组深度测序，建立恶性疟原虫三维基因组和转录组，并从RNA聚合酶Pol III启动子相关的转录因子TFIIIC入手，分析染色体上的各类基因在细胞核内不同染色质环境中定位时的表达状态，从而在更高层面上诠释疟原虫基因表达调控机制。该研究不仅将为最终阐明恶性疟原虫免疫逃避和致病机制提供新的理论依据，也将为疟疾的防治提供新的靶点和思路。

The infectious disease malaria transmitted by mosquito remains a serious threaten to global public health, and one of the human-infected malaria pathogens, Plasmodium falciparum, accounts for approximately one million death annually in the world currently. Its development, invasion, infection establishment and pathogenesis in host relies on the precise and complex regulation mechanism of gene expression, e.g. the mutually exclusive expression manner of multi-copy variant gene families, which is mainly regulated by epigenetic pathways at transcriptional level. However, many mechanistic details are still to be investigated. In this study, we aim to reveal the regulation pathway by establishment of 3D genome and transcriptome through chromosome conformation capture with high resolution and genome-wide chromatin mapping and deep sequencing of dynamic transcriptome, by which we are able to further investigate various gene expression status in distinct local chromatin environment based on a putative chromosome-binding and nuclear periphery localization factor, TFIIIC. We believe that this study will contribute to the elucidation of the mechanisms controlling those critical processes of malaria parasite development, antigenic variation, immune evasion, and pathogenesis in human host, and also help to the development of new intervention tools against this disease by providing new targets and strategies.