Molecular mechanism of organellar replication in Plasmodium falciparum

疟原虫体内有一个基本的非光合作用质体，称为顶质体。就像线粒体一样，顶质体有自己的基因组，顶质体DNA的准确复制对疟原虫的生存至关重要。顶质体复制是由一个专门的复制机制（复制体），这是从真核生物和细菌复制体不同。目前我们还不知道顶质体复制体的功能。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）沿着酶动力学和单分子生物物理学来开发顶质体基因组复制如何发生的第一个全面的图片。这项工作将对我们理解复制这一基本细胞过程产生重大影响，并将为下游研究提供信息，这些研究旨在开发抗疟疾药物，以对抗多药耐药疟原虫感染

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