Molecular mechanism of organellar replication in Plasmodium falciparum

疟原虫含有一种重要的非光合作用的质体，称为质外体。就像线粒体一样，质外体也有自己的基因组，准确复制质外体DNA对疟原虫的生存至关重要。顶体复制是由一种专门的复制机制(复制体)执行的，它既不同于真核细胞的复制，也不同于细菌的复制。目前，我们还不知道质外体复制体的功能。在这个跨学科的项目中，我们将使用单粒子低温电子显微镜(Cryo-EM)以及酶动力学和单分子生物物理学来开发第一张关于质外体基因组复制如何发生的全面图片。这项工作将对我们对复制的理解产生重大影响，复制是一个基本的细胞过程，也将为下游的研究提供信息，这些研究旨在开发抗疟疾药物来对抗耐多药疟原虫感染。

Plasmodium harbours an essential non-photosynthetic plastid called the apicoplast. Just like mitochondria, apicoplast has its own genome and accurate duplication of the apicoplast DNA is essential for Plasmodium survival. Apicoplast replication is performed by a dedicated replication machinery (replisome), which is divergent from both the eukaryotic and bacterial replisomes. At present we do not know how the apicoplast replisome functions. In this inter-disciplinary project we will use single particle cryo-electron microscopy (cryo-EM) along with enzyme kinetics and single molecule biophysics to develop the first comprehensive picture of how apicoplast genome duplication occurs. This work will have a major impact on our understanding of replication, a fundamental cellular process, and will also inform downstream research geared towards antimalarial drug development for combating multi-drug resistant Plasmodium infection