B1: Molecular mechanisms linking metabolism and chromatin remodelling in the human malaria parasite Plasmodium falciparum

B1: Molecular mechanisms linking metabolism and chromatin remodelling in the human malaria parasite Plasmodium falciparum

The protozoan parasite Plasmodium (P.) falciparum causes malaria by invading and manipulating human erythrocytes. For optimal transmission through its mosquito vector, the parasite needs to balance virulence and replication rate with the rate of differentiation into transmission stages. These decisions are governed by chromatin modifications and occur in response to environmental stimuli. However, it is unclear how the parasite senses environmental changes and how chromatin remodelling is achieved as a consequence. In this project we will test the hypothesis that microenvironment-induced metabolic reprogramming of P. falciparum parasites results in epigenetic changes that direct transcriptional differentiation programs. We will investigate how different conditions which P. falciparum encounters in the human host (hypoxia, acidosis, hemolysis, temperature, nutrient depletion) influence parasite acetyl-CoA metabolism and how this is reflected in the transcriptomic and epigenomic footprint by applying RNAseq and ChIPseq analyses. Further, we will use transgenic approaches to identify parasite proteins that are critical for chromatin remodelling processes in the malaria parasite.

Petter schema

 

Supervisor