• KRISHANPAL KARMODIYA

      Articles written in Journal of Biosciences

    • Role of PfGCN5 in nutrient sensing and transcriptional regulation in Plasmodium falciparum

      MUKUL RAWAT RASHIM MALHOTRA SHARVANI SHINTRE SAMARENDRA PANI KRISHANPAL KARMODIYA

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      Malaria is a deadly, infectious disease caused by the parasite Plasmodium, leading to millions of deathsworldwide. Plasmodium requires a coordinated pattern of sequential gene expression for surviving in bothinvertebrate and vertebrate host environments. As parasites largely depend on host resources, they also developefficient mechanisms to sense and adapt to variable nutrient conditions in the environment and modulate theirvirulence. Earlier we have shown that PfGCN5, a histone acetyltransferase, binds to the stress-responsive andvirulence-related genes in a poised state and regulates their expression under temperature and artemisinintreatment conditions in P. falciparum. In this study, we show upregulation of PfGCN5 upon nutrient stresscondition. With the help of chromatin immunoprecipitation coupled high-throughput sequencing (ChIP-seq)and transcriptomic (RNA-sequencing) analyses, we show that PfGCN5 is associated with the genes that areimportant for the maintenance of parasite cellular homeostasis upon nutrient stress condition. Furthermore, weidentified various metabolic enzymes as interacting partners of PfGCN5 by immunoprecipitation coupled withmass spectroscopy, possibly acting as a sensor of nutrient conditions in the environment. We also demonstratedthat PfGCN5 interacts and acetylates PfGAPDH in vitro. Collectively, our data provides important insights intotranscriptional deregulation upon nutrient stress condition and elucidate the role of PfGCN5 during nutrientstress condition.

    • Origin of RNA Polymerase II pause in eumetazoans: Insights from Hydra

      PULI CHANDRAMOULI REDDY SAURABH J PRADHAN KRISHANPAL KARMODIYA SANJEEV GALANDE

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      Multicellular organisms have evolved sophisticated mechanisms for responding to various developmental,environmental and physical stimuli by regulating transcription. The correlation of distribution of RNAPolymerase II (RNA Pol II) with transcription is well established in higher metazoans, however genome-wideinformation about its distribution in early metazoans, such as Hydra, is virtually absent. To gain insights intoRNA Pol II-mediated transcription and chromatin organization in Hydra, we performed chromatin immunoprecipitation(ChIP)-coupled high-throughput sequencing (ChIP-seq) for RNA Pol II and Histone H3. Strikingly,we found that Hydra RNA Pol II is uniformly distributed across the entire gene body, as opposed to itscounterparts in bilaterians such as human and mouse. Furthermore, correlation with transcriptome datarevealed that the levels of RNA Pol II correlate with the magnitude of gene expression. Strikingly, thecharacteristic peak of RNA Pol II pause typically observed in bilaterians at the transcription start sites (TSSs)was not observed in Hydra. The RNA Pol II traversing ratio in Hydra was found to be intermediate to yeastand bilaterians. The search for factors involved in RNA Pol II pause revealed that RNA Pol II pausingmachinery was most likely acquired first in Cnidaria. However, only a small subset of genes exhibited thepromoter proximal RNP Pol II pause. Interestingly, the nucleosome occupancy is highest over the subset ofpaused genes as compared to total Hydra genes, which is another indication of paused RNA Pol II at thesegenes. Thus, this study provides evidence for the molecular basis of RNA Pol II pause early during theevolution of multicellular organisms.

    • Analysis of drug resistance marker genes of Plasmodium falciparum after implementation of artemisinin-based combination therapy in Pune district, India

      AARTI OZARKAR ABHISHEK KANYAL SWATI DASS PRAKASH DESHPANDE DEEPTI DEOBAGKAR KRISHANPAL KARMODIYA

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      The global emergence and spread of malaria parasites resistant to antimalarial drugs is a major problem inmalaria control and elimination. In this study, samples from Pune district were characterized to determineprevalence of molecular markers of resistance to chloroquine (pfcrt codons C72S, M74I, N75E, K76T andpfmdr-1 N86Y, Y184F), pyrimethamine (pfdhfr C50R, N51I, C59R, S108N), sulfadoxine (pfdhps, S436A,A437G, K540E, A581G), and artemisinin (pfkelch13, C580Y, R539T). The pfcrt K76T mutation was found in78% samples as CVMNT, SVMNT and CVIET haplotype. The pfmdr-1 N86Y and Y184F mutations werefound in 54% of samples. The pfdhfr double mutation C59R + S108N was present in 67% of samples, whilethe pfdhfr triple mutation (N51I + C59R + S108N) was not detected. The pfdhps mutations A437G andK540E were found in 67% of samples. Single mutants of pfdhps were rare, with K540E detected in only 6patient samples. Similarly, pfdhps A581G was found in 13 of the isolates. The molecular markers associatedwith artemisinin resistance (mutations in pfkelch13 C580Y, R539T) were not detected in any of the isolates.These results suggest an emerging problem with multidrug-resistant P. falciparum. Though the genotypeconventionally associated with artemisinin resistance was not observed, chloroquine-resistant genotype hasreached complete fixation in the population. Moreover, the prevalence of mutations in both pfdhfr and pfdhps,with the presence of the quadruple mutant, indicates that continued monitoring is required to assess whethersulfadoxine-pyrimethamine can be used efficiently as a partner drug for artemisinin for the treatment of P.falciparum.

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