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., Design of a basigin-mimicking inhibitor targeting the malaria invasion protein RH5, Proteins: Structure, Function, and Bioinformatics, ISSN:0887-3585
et al., Plasmodium myosin a drives parasite invasion by an atypical force generating mechanism, Nature Communications, ISSN:2041-1723
et al., Stable knockout and complementation of receptor expression using in vitro cell line derived reticulocytes for dissection of host malaria invasion requirements, Nature Communications, ISSN:2041-1723
et al., 2019, The antimalarial screening landscape-looking beyond the asexual blood stage, Current Opinion in Chemical Biology, Vol:50, ISSN:1367-5931, Pages:1-9
et al., 2019, Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites., Plos Pathog, Vol:15