DNA damage regulation and its role in drug-related phenotypes in the malaria parasites.
Ontology highlight
ABSTRACT:
ORGANISM(S): Plasmodium falciparum
SUBMITTER: Devendra Gupta
PROVIDER: E-GEOD-72580 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Drug resistance in Plasmodium falciparum remains a challenge for the malaria eradication programs around the world. With the emergence of artemisinin resistance, the efficacy of the partner drugs in the artemisinin combination therapies (ACT) that include quinoline based drugs is becoming critical. So far only few resistance markers have been identified and verified from which only two ABC transmembrane transporters namely PfMDR1 and PfCRT have been experimentally verified. Another P. falciparum ABC transporter, the multidrug resistance-associated protein (PfMRP2) represents an additional possible factor of drug resistance in P. falciparum. In this study, we identify a parasite clone that is derived from the 3D7 P. falciparum strain and which shows increased resistance to chloroquine and mefloquine through the trophozoite and schizont stages. We demonstrate that the resistance phenotype is caused by a 4.1 kb deletion in the 5M-bM-^@M-^Y upstream region of the pfmrp2 gene that leads to an alteration in the pfmrp2 transcription that result in increased levels of PfMRP2 protein. These results also suggest the importance of putative promoter elements in regulation of gene expression during the P. falciparum intra-erythrocytic developmental cycle and the potential of such genetic polymorphisms to underlie drug resistance phenotypes. Presented here are the data from microarray-based genome-wide transcriptomic and genomic studies of the drug-sensitive and drug-resistant 3D7 clones 11C/wt and 6A/mut. 2 P. falciparum lab clones derived from 3D7 strain were harvested during the intra-erythrocytic cycle at 8hr intervals over 48 hours to obtain a total of 6 time point samples per clone. RNA from a total of 12 samples were extracted. Synthesis of target DNA was carried out as described in Bozdech, Z., S. Mok & A. P. Gupta, (2013) DNA microarray-based genome-wide analyses of Plasmodium parasites. Methods in molecular biology 923: 189-211 and used in replicate microarray hybridizations against a common RNA reference pool of 3D7 strain.
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-02-07 | E-GEOD-44129 | biostudies-arrayexpress
Project description:The goal of our study is to characterize the global transcriptional resposne of P.falciparum to DNA damageing agents. Alongside, we stidied the epigenetic regulation of DNA damage resposne in parasite. Further, we studied the mecanism which underlined the ARMD (mutator) phenotype of P. falciparum. In order to elucidate the transcriptiona resposne to DNA damage, P. falciparum 3D7 parasites were treated with 4 perturbating agents for 6 hours. We mapped the global nucleosome occupancy for 3 most responsive histone modifications to DNA damage by chromatin immunoprecipitation coupled with DNA microarray (ChIP-on-chip). In order to identify the transcriptional similarities between artemesinin and MMS, we carried out 6 hours of artemesinin treatment in triplicates and compared with triplicate dataset of MMS.
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Project description:The goal of our study is to characterize the global transcriptional resposne of P.falciparum to DNA damageing agents. Alongside, we stidied the epigenetic regulation of DNA damage resposne in parasite. Further, we studied the mecanism which underlined the ARMD (mutator) phenotype of P. falciparum. In order to elucidate the transcriptiona resposne to DNA damage, P. falciparum 3D7 parasites were treated with 4 perturbating agents for 6 hours. We mapped the global nucleosome occupancy for 3 most responsive histone modifications to DNA damage by chromatin immunoprecipitation coupled with DNA microarray (ChIP-on-chip). In order to identify the transcriptional similarities between artemesinin and MMS, we carried out 6 hours of artemesinin treatment in triplicates and compared with triplicate dataset of MMS.
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Project description:The objective of our study is to characterize gene expression signatures associated with in vivo artemisinin-resistance phenotype in this large-scale genome-wide association study. To achieve this goal, we employed microarray technology to establish the global gene expression profiles of isolates sampled from 1043 patients, of whom after treatment with ACTs (artemisinin combination therapy) displayed differential rates of parasite clearance. P. falciparum isolates were sampled from the whole blood of 1043 malaria-infected patients prior to ACT treatment. Sampling was done across 14 field sites spanning across South East Asia (Pailin, Pursat, Preah Vihear, Rattanakiri in Cambodia; Mae Sot, Srisakhet, Khun Han, Ranong in Thailand; Shwe Kyin in Myanmar; Binh Phuoc in Vietnam; Attapeu in Laos), to Bangladesh and African DR Congo from 2010 to 2012. RNA were extracted and synthesis and amplification of target DNA was carried out as described in Bozdech, Z., S. Mok & A. P. Gupta, (2013) DNA microarray-based genome-wide analyses of Plasmodium parasites. Methods in molecular biology 923: 189-211 (PMID 22990779), to generate sufficient material for hybridizations against a common RNA reference pool of 3D7 strain using a microarray platform.
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Project description:Drug resistance in Plasmodium falciparum remains a challenge for the malaria eradication programs around the world. With the emergence of artemisinin resistance, the efficacy of the partner drugs in the artemisinin combination therapies (ACT) that include quinoline based drugs is becoming critical. So far only few resistance markers have been identified and verified from which only two ABC transmembrane transporters namely PfMDR1 and PfCRT have been experimentally verified. Another P. falciparum ABC transporter, the multidrug resistance-associated protein (PfMRP2) represents an additional possible factor of drug resistance in P. falciparum. In this study, we identify a parasite clone that is derived from the 3D7 P. falciparum strain and which shows increased resistance to chloroquine and mefloquine through the trophozoite and schizont stages. We demonstrate that the resistance phenotype is caused by a 4.1 kb deletion in the 5M-bM-^@M-^Y upstream region of the pfmrp2 gene that leads to an alteration in the pfmrp2 transcription that result in increased levels of PfMRP2 protein. These results also suggest the importance of putative promoter elements in regulation of gene expression during the P. falciparum intra-erythrocytic developmental cycle and the potential of such genetic polymorphisms to underlie drug resistance phenotypes. Presented here are the data from microarray-based genome-wide transcriptomic and genomic studies of the drug-sensitive and drug-resistant 3D7 clones 11C/wt and 6A/mut. 2 P. falciparum lab clones derived from 3D7 strain were harvested during the intra-erythrocytic cycle for genomic DNA. gDNA were extracted by phenol chloroform. Synthesis of labelled target DNA was carried out as previously described: Bozdech, Z., M. Llinas, B. L. Pulliam, E. D. Wong, J. Zhu & J. L. DeRisi, (2003) The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biol 1: E5, and used in comparative genomic microarray hybridizations (CGH).
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