Research
Our current quest is to understand how malaria parasites reproduce asexually within red blood cells. The parasite undergoes an extraordinary form of cell division called schizogony, where the parasite’s nucleus divides multiple times before the entire cell splits all at once, producing up to 24 daughter parasites. Many features of this process remain a mystery. How does the parasite know when to start dividing? How does it time each step in this process? And how does it know when to stop after making a certain number of daughter parasites? We want to understand how these crucial decisions are made and identify the molecules and mechanisms involved. We hope that this will lead to new insights into how the parasite proliferates in the blood - the primary cause of clinical symptoms - and eventually to developing new drugs to combat this devastating disease.
To survive and multiply within red blood cells, the malaria parasite relies on nearly half of its ~5000 protein-coding genes. However, we still do not know what many of these important genes do. Studying these essential genes is difficult because of the parasite’s haploid nature. We use the inducible Dimerisable Cre (DiCre)-lox system to precisely knock out target genes at desired stages of the replication cycle in the most lethal human malaria parasite, Plasmodium falciparum. This enables us to analyse the resulting phenotypes in a population of mutant parasites in a controlled manner through multi-omics strategies, live-cell time-lapse imaging, and detailed biochemical and molecular analyses. Recently, we developed a scalable refinement of this system called frameshift-based trackable inducible knockout (SHIFTiKO) that now allows us to conduct targeted inducible knockout screens of groups of essential genes, thereby speeding up gene function discovery.
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