Molecular mechanism of organellar replication initiation in Plasmodium falciparum

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 electron cryomicroscopy (cryoEM) along with single molecule fluorescence resonance energy transfer (smFRET) to develop a comprehensive picture of how apicoplast genome duplication occurs, focusing specifically on the initial steps of replication.

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.