Targeting the unique circular RNA biology in malaria parasites

Plasmodium falciparum malaria persists as one of the most important infectious diseases in the world despite major eradication efforts.

One central obstacle to these efforts is the parasite’s incredibly rapid, but mechanistically highly elusive, phenotypic plasticity.

We were the first to identify circular RNA (circRNA) in the parasite and have thereafter generated data that makes us hypothesize that they are highly important gene regulatory molecules of potential therapeutic interest.

The current proposal builds upon these findings and aims at scrutinizing this class of molecules for their biogenesis, host-adaptive potential and to explore whether novel ways to target these molecules are of in vivo relevance.

This work will be performed by a doctoral student and a postdoctoral fellow, in synergy with the rest of the Ribacke lab.

Initially, we will follow up on preliminary data that suggest RNA modifications to be involved in the highly unique biogenesis of parasite circRNA.

In addition, we will target enzymes predicted to be involved in these modifications by advanced reverse genetics approaches.

We will thereafter perform small RNA sequencing of clinical isolates from children with malaria and correlate the findings to known plasma metabolomes, proteomes and parasite clearance rates of the patients.

Lastly, we plan to explore the therapeutic potential by targeting circRNA in rodent malaria parasites using a novel delivery system for specific antisense oligonucleotides.