Life Sciences & Biotechnology
Title : | Molecular chaperone mediated cellular homeostasis of Ribonucleotide Reductase: implications on Plasmodium falciparum replication |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. sunanda Bhattacharyya, University Of Hyderabad, Telangana |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | sbtsl@uohyd.ernet.in |
Equipments : | Pipettes
Refrigerated High speed Micro Centrifuge
Dry Bath Incubator |
Details
Executive Summary : | 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. |
Total Budget (INR): | 50,48,999 |
Organizations involved