Chromatin Dynamics in Plasmodium falciparum

Plasmodium falciparum, a unicellular eukaryotic parasite, causes the most severe and deadly form of the human disease malaria. In 2019, 229 million cases of malaria infection with about 409,000 deaths were reported, mainly affecting children under the age of five. Effective therapeutics to treat Malaria are still missing.

The highly complex life cycle of the human malaria parasite, Plasmodium falciparum, is based on an orchestrated and tightly regulated gene expression program. In general, eukaryotic transcription regulation is determined by a combination of sequence-specific transcription factors binding to regulatory DNA elements and the packaging of DNA into chromatin as an additional layer. The accessibility of regulatory DNA elements is controlled by the nucleosome occupancy and changes of their positions by an active process called nucleosome remodeling. These epigenetic mechanisms are poorly explored in P. falciparum. The parasite genome is characterized by an extraordinarily high AT-content and its distinct architecture of functional elements. Furthermore, its chromatin-related proteins also exhibit high sequence divergence compared to other eukaryotes. Combined with the specific biochemical properties of plasmodium nucleosomes, these features suggest substantial differences in chromatin-dependent regulation.

The Laengst Group studies these chromatin differences, investigating whether epigenetics is the weak spot to treat this deadly disease.

We just identified PfSnf2L as a drug target and developed a small molecule drug that can serve as a basis for novel, transmission blocking therapeutics. See our recent publication: Watzlowik et al., Nature 2025.