Seminar by a new researcher: Dr Flore NARDELLA

Dr Flore NARDELLA

Laboratoire de chimie de coordination

Using epidrugs to understand the role of epigenetics in artemisinin-induced quiescence in P. falciparum

Malaria is still responsible for 262 million cases and 610,000 fatalities in 2024 according to the World Health Organization (WHO), with 95% of deaths occurring in the African region (WHO). Resistance of Plasmodium falciparum to artemisinin has recently been observed in Africa and threatens the efficacy of the artemisinin-based combination therapies, the reference treatment. Artemisinin-resistance is singular, because only a fraction of the parasite population is able to enter quiescence, while the whole population carries a mutation in the molecular marker of resistance kelch13. This suggests that epigenetic regulation may be involved in the preparedness of the parasite to enter quiescence. Using a small library of epidrugs, we’ve shown that inhibitors of histone methylation (BIX-01294 and TM2-115) and histone acetylation (Apicidin, JV1821) are active against quiescent parasites. These inhibitors will help us to decrypt the epigenetic marks and their gene targets that are associated with quiescence, in order to develop new drugs targeting these pathways.