Shedding a super-resolution light on mitochondrial fission during schizogony in human malaria parasites
Malaria parasites multiply through an unusual and tightly orchestrated process termed schizogony, which leads to the simultaneous formation of up to 32 parasites in a single infected red blood cell and even thousands of daughter cells during mosquito- or liver-stage development. During schizogony, organelles like the mitochondrion and apicoplast are almost instantly divided and distributed over the daughter parasites. However, the mechanism behind mitochondrial fission and the key proteins involved remain unknown.
The aim of this project is to unravel the mechanism underlying mitochondrial fission in the human malaria parasite Plasmodium falciparum during schizogony. Therefore, we will develop and apply advanced microscopic techniques. We will use a number of readily available mutant lines and apply CRISPR/Cas9 to generate others, including mutants harbouring gene deletions, conditional knockdowns, tagged proteins, and strongly fluorescent organelle markers. We will study these parasites using a combination of live imaging and super-resolution microscopy, including STORM and SR-CLEM. Using different methods we will attempt to identify interacting proteins. This will shed light on the mechanisms underlying mitochondrial fission in P. falciparum and serve as a base for further investigation into this process as a potential antimalarial drug target.
(The picture shows the mitochondrion of a live P. berghei asexual blood stage trophozoite labelled with the organelle targeted red fluorescent protein mCherry. Image recorded by Joachim Matz.)
Taco Kooij 