Life Sciences & Biotechnology
Title : | Deciphering the structural and functional attributes of the putative nucleoplasmin from Plasmodium falciparum |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Dileep Vasudevan, Rajiv Gandhi Centre For Biotechnology (RGCB), Kerala |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | dileepvasudevan@gmail.com |
Details
Executive Summary : | Malaria, a major global public health concern, is caused by the parasite Plasmodium falciparum, transmitted to humans through an infected mosquito. Current treatments include quinone drugs that inhibit nucleic acid synthesis, protein synthesis, and glycolysis, interfering with hemoglobin digestion in the schizont stage. However, parasitic defense and adaptation have made these drugs less effective, necessitating the discovery of new targets. The parasite's high mutation rate and tightly regulated gene expression provide a selective advantage to its survival. Investigating chromatin dynamics associated with the parasite's developmental stages would significantly advance our knowledge of chromatin dynamics and its association with gene expression regulation in P. falciparum. P. falciparum has an uncharacterized protein, a putative nucleoplasmin (PfNPM), that could be a functional histone chaperone for the parasite, aiding its chromatin assembly and dynamics. PfNPM exhibits differential expression patterns in different blood stages of the parasite, corroborating previous nucleosomal occupancy and chromatin accessibility studies. This study aims to explore the oligomeric nature, stability, and in vitro histone binding and chaperoning properties of PfNPM. The structural characterization of PfNPM and its complexes with histone oligomers will be investigated using XRD, Cryo-EM, and sAXs, while the chromatin association and role of PfNPM in transcription regulation will be explored using ChIP-seq followed by RT-PCR. The knock-out studies of PfNPM will reveal the molecular mechanisms of histone interaction, storage, and deposition onto the DNA, governing chromatin accessibility in the parasite. |
Co-PI: | Dr. Viswanathan Arun Nagaraj, Institute Of Life sciences (ILs), Bhubaneswar, Odisha-751021, Dr. Rajesh Chandramohanadas, Rajiv Gandhi Centre For Biotechnology (RGCB), Kerala-695014 |
Total Budget (INR): | 51,53,328 |
Organizations involved