DAAD project: Comparative mapping of the DNA-methylation status of the malaria parasite

 

Duration: 3 years

Application period: since 2019

Scholar: Jean-Pierre Musabyimana

Summary:

The vector-borne malaria tropica is still a major health burden worldwide. The disease is caused by the unicellular parasite Plasmodium falciparum, which in humans replicates in the red blood cells, leading to anaemia, fever and organ failure. P. falciparum depends on the well-coordinated regulation of gene expression for development and propagation both in its human host and the mosquito vector. The molecular mechanisms of transcriptional control, however, are to date not well understood. Increasing evidence indicates that epigenetic regulation largely contributes to transcriptional control of gene expression. While recent studies dealt with histone modifications during the erythrocytic replication phase of P. falciparum, to date there is hardly any data on gene regulation via DNA methylation. The project therefore aims to compare the DNA methylation status of the P. falciparum asexual blood stages and of gametocytes, sexual precursor cells crucial for human-to-mosquito transmission, using a novel sequencing method based on nanopores, which allows reading DNA methylation without the need of chemical treatments. Furthermore, the function of the plasmodial DNA methyltransferase PfDNMT during these DNA methylation changes will be evaluated, using a novel mRNA-destabilizing gene-knock down technique. Data gained by this study will provide novel insights into DNA methylation-mediated gene regulation by P. falciparum.