The role of non-coding RNAs and ribosomal RNAs in regulating gametocyte development in malaria parasites

• Applicant: Dr. Janne Grünebast
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 549182383

Malaria is a mosquito-borne tropical disease caused by parasites of the genus Plasmodium. Malaria remains one of the biggest threats to global health, with around 250 million people suffering from malaria in 2022 and 600,000 deaths. In particular, the pathogen Plasmodium falciparum is responsible for 80% of malaria deaths, mostly in children under the age of 5 in Africa. Plasmodium parasites have a complex life cycle that exposes them to various environmental conditions. In humans, parasites injected by a mosquito bite develop in the liver before entering the bloodstream, where they multiply asexually in red blood cells, causing the clinical symptoms of malaria. Some blood-stage parasites can enter the sexual phase and develop into gametocytes. The gametocytes are quiescent forms waiting to be picked up by an Anopheles mosquito and eventually develop into sporozoites, which are transmitted again. In gametocytes stage V and sporozoites, both quiescent parasite stages awaiting transmission, the translation of proteins required from development in the next host is inhibited, but only a limited number of mechanisms have described how translational repression is regulated.First, this project aims to investigate the role of non-coding RNAs in regulating gametocyte development. Second, I will analyze the regulation of translational repression in quiescent parasite stages and, more specifically, the role of ribosomal RNA and non-coding RNAs in this process. I will use Oxford Nanopore technologies to directly sequence RNA without a reverse transcription step, allowing me to robustly identify non-coding RNAs for all blood stages in a stage-specific and genome-wide manner. Bioinformatic analyses and the application of duplex RNA sequencing for identifying binding partners of the non-coding RNAs will enable me to characterize the functions of these non-coding RNAs and reveal their importance for the regulation of translational repression, as well as for the control of transcription. Using the long reads of ONT sequencing, I will also analyze the synthesis, degradation, and switch between different rRNA types during gametocyte development and demonstrate the significance of these molecules in the repression of translation.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. David Serre