Organisation of the invasion machinery in the Plasmodium parasite
Year of award: 2022
Dr Clinton Lau
University of Oxford, United Kingdom
The malaria-causing Plasmodium parasite relies on its invasive organelles to enter host cells. These organelles, the rhoptries and micronemes, must cluster at the apical end of the parasite and discharge their contents at specific times during invasion. The shape and localisation of these organelles are determined by filamentous assemblies. Helical filaments in the rhoptry and microneme lumens template their shape, but the protein which forms these filaments remains unidentified. The parasite?s microtubule array is implicated in the transport of micronemes to their functional location. However, how microtubule-binding proteins organise this array is not understood and the proteins that transport micronemes have yet to be established. Here I propose to investigate how the Plasmodium invasive organelles are organised using a combination of cryogenic electron microscopy, mass spectrometry, CRISPR/Cas9 and biochemical assays. I will identify the luminal helices and dissect their shape-determining mechanism. I will solve the structure of the microtubule array and characterise the links to other structures in the cell. Finally I will identify the proteins responsible for microneme transport. My research will uncover principles of organelle organisation and transport relevant across eukaryotes, and will reveal unique aspects in Plasmodium that could be targeted by novel therapeutics.