Molecular mechanism of organellar replication in Plasmodium falciparum

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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