Malaria 7: Ganter

Research interest

Cells usually multiply by duplicating their genome and divide themselves into two daughter cells. Yet, in some organisms cellular multiplication follows distinct, somewhat bizarre routes. One of these rather unusual ways can be seen in Plasmodium parasites, the causative agents of malaria, which remains a major scourge of humanity.

The genus name reflects the parasite’s unique way of multiplication. In 1885 Italian physicians Celli and Marchiafava proposed the genus name Plasmodium for malaria parasites, as the parasites reminded them of a plasmodium,a form within the life cycle of some simple organisms such as slime moulds, typically consisting of a mass of protoplasm containing many nuclei’ (Oxford Dictionary). Indeed, inside erythrocytes the parasites form a multinucleated cell before daughter cell are assembled.

An unusual feature of Plasmodium replication inside erythrocytes, known as schizogony, is the number of nuclei and, hence, daughter cells they produce during one round of intracellular replication (Fig. 1). Parasites with 20 nuclei can be readily found. Divergence from a geometric expansion, which would lead to 2, 4, 8,16, or 32 daughter cells, is accompanied by asynchronous replication. This suggests that nuclei control their own replication until a global mechanism takes over and co-ordinates the final round of nuclear division with daughter cell formation. This is in striking contrast with nuclear division in other multinucleated cells, such as the early Drosophila embryo, where nuclei follow a geometric expansion, as their division is relatively synchronous.

To gain insight into the regulators of Plasmodium falciparum schizogony, we conducted a forward genetic screen for the conditional protein expression of all protein kinases expressed during schizogony and identified a kinase as essential for proliferation (Fig. 2). This kinase is Plasmodium-specific and a crucial regulator of the continuous rounds of DNA replication, histone modification, and regulation of gene expression. We also found that this kinase is required for transmission to the mosquito. This work serves as a starting point to gain a better understanding of Plasmodium replication biology.

We are currently using the rodent-malaria model Plasmodium berghei to investigate parasite replication in Anopheles mosquitos and the subsequent parasite replication in the liver-stage of infection. In the human pathogen Plasmodium falciparum, we are using genetic tools to uncover the signalling cascade that orchestrate parasite multiplication in the blood stage of infection. Furthermore our previous work suggests that a set of unknown genes is involved in parasite replication. We are using classical reverse genetic tools and inducible gene-depletion approaches to characterise the function of these unknown genes.

Our overall aim is to elucidate the regulatory mechanisms that govern Plasmodium replication and, in turn, understand a cell cycle that seemingly cannot be explained by current models of cell cycle regulation.





Centre for Infectious Diseases, Parasitology

Heidelberg University Hospital 

Im Neuenheimer Feld 324 (office & labs in INF 345)

69120 Heidelberg


Phone:+49 (0)6221 567438



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