How does the apicomplexan dynein complex mediate transport of micronemes in malaria parasite P. falciparum?

Abstract
Plasmodium falciparum is the apicomplexan parasite responsible for the most severe form of human malaria. Parasitic invasion of host cells requires precise positioning of two organelles: the rhoptries and the micronemes. Microneme positioning is thought to be driven by the motor protein dynein and the adaptor complex FHF. Neither complex is entirely well conserved and direct evidence for transport is lacking. This project aims to elucidate the mechanism of microneme transport by providing molecular detail of the P. falciparum dynein complex and the FHF adaptor. The first objective will be characterise the P. falciparum dynein-dynactin complex. The second objective will be to identify the components which make up the P. falciparum FHF complex and its microneme receptor. The final objective will be to obtain structural insight into how the FHF may engage its receptor via single particle cryo-EM. This project may provide key insight into how the malaria parasite prepares for invasion of the host cell but may also expand our understanding of eukaryotic motor proteins beyond the somewhat limited scope of metazoan model organisms. Potential divergence of transport machinery in apicomplexa may also allow for design of drugs and therapies targeting a range of diseases in humans and livestock.
UKRI-BBSRC Priorities
This project addresses the BBSRC objective of advancing the frontiers of bioscience discovery by understanding the rules of life. The potential evolutionary divergence of the dynein transport machinery in P. falciparum offers the opportunity to broaden our understanding of molecular motors beyond the somewhat limited scope of metazoans and yeast. It may also allow design of novel drugs for targeting P. falciparum and other apicomplexan parasites including livestock pathogens such as Eimeria tenella, thus adressing the BBSRC priority of animal health.