Throughout its complex lifecycle the malaria parasites, from the genus Plasmodium, must traverse tissues and invade a diversity of host cells to ensure successful propagation of their lifecycle. Each lifecycle stage is exquisitely designed for cell movement, tissue targeting and host cell invasion, yet we still do not understand the basic mechanics of how the parasite motor produces force and translates this into powerful movement or cell penetration. Unlike all other eukaryotic cells, the malaria parasites rely on an internal actin-myosin motor, linked through to the outside world through secreted surface adhesins across which it literally glides.
Our lab is focused on reconstructing Plasmodium gliding motor function in vitro, its regulation and in a cellular context exploring how the core factors that control motility are distributed. Our work covers the spectrum of scales from single molecule through to whole cell, biochemistry through structural biology and cell biology and, since moving to Imperial, the mysterious world of biophysics.
Ultimately our goal is to break apart Plasmodium motility at every level to generate fundamental understanding into parasite biology and identify potential targets to stop the parasite dead in its tracks!
et al., 2020, Peptide probes for Plasmodium falciparum MyoA tail interacting protein (MTIP): exploring the druggability of the malaria parasite motor complex, Acs Chemical Biology, Vol:15, ISSN:1554-8929, Pages:1313-1320
Ashdown G, Gaboriau D, Baum J, A machine learning approach to define antimalarial drug action from heterogeneous cell-based screens, Science Advances, ISSN:2375-2548
et al., 2020, Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum, Science Advances, Vol:6, ISSN:2375-2548
et al., 2020, A biosynthetic platform for antimalarial drug discovery, Antimicrobial Agents and Chemotherapy, Vol:64, ISSN:0066-4804, Pages:1-9
et al., 2020, Structure-activity relationship studies of a novel class of transmission blocking antimalarials targeting male gametes., Journal of Medicinal Chemistry, Vol:63, ISSN:0022-2623, Pages:2240-2262