Last Updated: 18/06/2024
Targeting the unique circular RNA biology in malaria parasites
Objectives
The current project builds upon previous findings and aims at scrutinizing circular ribonucleic acid (circRNA) and similar class of molecules for their biogenesis, host-adaptive potential and to explore whether novel ways to target these molecules are of in vivo relevance.
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. This team were the first to identify circular RNA (circRNA) in the parasite and have thereafter generated data that makes the researchers hypothesize that they are highly important gene regulatory molecules of potential therapeutic interest. This work will be performed by a doctoral student and a postdoctoral fellow, in synergy with the rest of the Ribacke lab. Initially, the team will follow up on preliminary data that suggest RNA modifications to be involved in the highly unique biogenesis of parasite circRNA. In addition, the team will target enzymes predicted to be involved in these modifications by advanced reverse genetics approaches. The researchers 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, the researchers plan to explore the therapeutic potential by targeting circRNA in rodent malaria parasites using a novel delivery system for specific antisense oligonucleotides.
Jan 2023 — Dec 2026
$459,857
