Research Projects

Malaria, a severe disease caused by the Plasmodium species, has a global prevalence of 229 million cases, with 409,000 deaths in 2019. Chemotherapy is crucial for controlling and managing malaria, but drug-resistant strains have impeded its effectiveness. Combination therapy is currently the best approach, but the regulation of enzymes within the parasite is crucial. Ribonucleotide reductase (RNR) is an excellent anti-malaria target due to its structural differences and importance during DNA synthesis and cell division. This proposal focuses on the chaperone-cochaperone complex in P. falciparum, which regulates the cellular abundance and activity of this enzyme. The study aims to understand whether the Hsp90-Hsp70 chaperone system, particularly Hsp70 cochaperone Pf14_0359, is involved in providing stability to PfRNR. Inhibiting the interaction between Pf14_0359 and PfHsp70 or PfHsp90/PfHsp70 function could destabilize PfRNR and increase the efficacy of existing drugs targeting PfRNR. The hypothesis is that PfHsp70-PfHsp90 chaperone machinery regulates PfRNR activity and plays a crucial role in arresting parasite replication. The study hypothesizes that simultaneous use of two different inhibitors targeting either chaperone-cochaperone interaction/chaperone activity along with targeting PfRNR catalytic activity can be employed to arrest parasite growth more efficiently.