HmC-like in Plasmodium
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ABSTRACT:
PROVIDER: PRJEB29536 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A new hydroxymethylcytocine-like DNA modification linked to gene expression is the predominant cytosine modification in malaria parasites
| PRJEB32602 | ENA
Project description:PfEMP1 is a variable antigen displayed on red blood cells (RBCs) infected with the malaria parasite Plasmodium falciparum. PfEMP1 mediates binding of the infected cell to the endothelium of blood vessels, a major cause of severe manifestations of malaria. Each parasite encodes ∼60 different PfEMP1 variants of which only one is expressed at a time and switching between variants underlies immune evasion in the host and variant-specific severity of disease. PfEMP1 expression heterogeneity between parasites complicates its study and hampers genetic modification approaches as in many cells the modified locus is not expressed. Here we used selection linked integration to generate parasites all expressing the same PfEMP1 variant and permitting genomic modification of the expressed locus. Using this system, we study PfEMP1 trafficking, generate cell lines binding to all major endothelial receptors, survey the protein environment from functional PfEMP1 in the host cell and identify new proteins needed for PfEMP1 mediated sequestration. Overall, these approaches facilitate the study of the molecular and cellular biology of the key virulence factor of malaria parasites.
2024-09-01 | GSE275671 | GEO
Project description:Variation of surface adhesins is a critical mediator of virulence and immune evasion in many medically important microbes. Phenotypic switching has been linked to transcriptional changes and the function of chromatin proteins, but the determinants of the rate of phenotypic switching remain poorly defined. We analyzed epigenetic switching of the Plasmodium falciparum erythrocyte invasion ligand PfRh4. By introducing a prokaryotic Dam methylase, we demonstrate that parasites selected for in vivo PfRh4 activation show a reversible increase in promoter accessibility while exhibiting perinuclear repositioning of the locus from a silent to a conserved activation domain. Forced activation of a proximal gene results in a similar level of repositioning of the PfRh4 locus into this domain and a concomitant increase in PfRh4 activation in a sub-population of parasites, with promoter accessibility occurring only at actively transcribed loci. Thus, we reveal two distinct epigenetic mechanisms regulating the expression of a malaria virulence gene. To examine the correlation between changes in gene expression induced by treatment with a high dose of trichostatin A (TSA) and the associated changes in chromatin accessibility. Plasmodium falciparum was treated (or not, control) with 100nm or 500nm TSA, and then the expression profiles were analyzed.
2012-10-13 | E-GEOD-41567 | biostudies-arrayexpress
Project description:Malaria parasites have evolved a well-adjusted developmental program to progress through the complex life cycle in the human and mosquito host. Here we identify cytosine methylation of tRNAAsp (GTC) as being critical to maintain stable protein synthesis under cellular stress. Using conditional knock out of a member of the DNA methyltransferases family called Pf-DNMT2, RNA bisulfite sequencing demonstrates the selective cytosine methylation of this enzyme of tRNAAsp (GTC) at position C38. Although no growth defect on parasite asexual proliferation was observed, Pf-DNMT2 KO parasites show a striking increase in their sexual commitment and an increased sensitivity to Dihydroartemisinin. In mutant parasites we observe a dramatic decrease of tRNAAsp (GTC) when compared to non-stressed parasites and mass spectrometry analysis shows the selective downregulation of proteins with GAC codon bias. Here we identify an epitranscriptomic mechanism that safeguards protein translation and homeostasis of sexual commitment during cellular stress in malaria parasites
2022-02-13 | PXD024769 | Pride
Project description:Variation of surface adhesins is a critical mediator of virulence and immune evasion in many medically important microbes. Phenotypic switching has been linked to transcriptional changes and the function of chromatin proteins, but the determinants of the rate of phenotypic switching remain poorly defined. We analyzed epigenetic switching of the Plasmodium falciparum erythrocyte invasion ligand PfRh4. By introducing a prokaryotic Dam methylase, we demonstrate that parasites selected for in vivo PfRh4 activation show a reversible increase in promoter accessibility while exhibiting perinuclear repositioning of the locus from a silent to a conserved activation domain. Forced activation of a proximal gene results in a similar level of repositioning of the PfRh4 locus into this domain and a concomitant increase in PfRh4 activation in a sub-population of parasites, with promoter accessibility occurring only at actively transcribed loci. Thus, we reveal two distinct epigenetic mechanisms regulating the expression of a malaria virulence gene. To examine the correlation between changes in gene expression induced by treatment with a high dose of trichostatin A (TSA) and the associated changes in chromatin accessibility.
2012-10-13 | GSE41567 | GEO
Project description:The ability to sense, respond and adapt to changes in nutrient availability is a survival requisite. This might be particularly important for malaria parasites, which encounter major alterations in nutrients levels throughout infection. How these parasites deal with nutrient fluctuations and maintain infection without killing their hosts before transmission remains unknown. Here, we show that blood-stage malaria parasites respond to dietary-restriction through a rearrangement of their transcriptome accompanied by a significant reduction in their multiplication rate. A kinome analysis combined with chemical and genetic approaches identified KIN, a putative AMP-activated kinase homologue, as a master regulator that senses host nutrients both in vitro and in vivo, and mediates the transcriptional response to the host nutritional status. Diet-responsive genes include the plant-like ApiAP2 transcription regulators, which appear to act as downstream effectors of KIN. Overall, these findings reveal key components of a parasite nutrient-sensing mechanism that is critical to modulate replication and virulence in malaria parasites.
2017-07-14 | GSE69627 | GEO
Project description:The dry season is a major challenge for Plasmodium falciparum parasites in many malaria endemic regions, where water availability limits mosquitoes to only part of the year. How P. falciparum bridges two transmission seasons months apart, without being cleared by the host or compromising host survival is poorly understood. Here we show that low levels of P. falciparum parasites persist in the blood of asymptomatic Malian individuals during the 5- to 6-month dry season, rarely causing symptoms and minimally affecting the host immune response. Parasites isolated during the dry season are transcriptionally distinct from those of subjects with febrile malaria in the transmission season, reflecting longer circulation within each replicative cycle, of parasitized erythrocytes without adhering to the vascular endothelium. Low parasite levels during the dry season are not due to impaired replication, but rather increased efficiency of splenic clearance of longer-circulating infected erythrocytes. We propose that P. falciparum virulence in areas of seasonal malaria transmission is regulated so that the parasite decreases its endothelial binding capacity, allowing increased splenic clearance and enabling several months of subclinical parasite persistence.
2020-08-20 | GSE148125 | GEO
Project description:During the malaria infection, Plasmodium parasites invade the host’s red blood cells where they can differentiate into two different life forms. The majority will replicate asexually and infect new erythrocytes. A small percentage, however, will transform into gametocytes – a specialized sexual stage able to survive and develop when taken up by Anopheles mosquito. As the gametocytes ensure the parasite’s transmission to a new host, their generation is an attractive target for new antimalarial interventions. The molecular mechanisms controlling gametocytogenesis, however, remain largely unknown due to the technical challenges: the early gametocytes are morphologically indistinguishable from asexual parasites and present in very low numbers during the infection. Recently, AP2-G - a transcription factor from an apicomplexa-specific apiAP2 family – was described as indispensable for gametocyte commitment in both human malaria parasite Plasmodium falciparum and rodent malaria model Plasmodium berghei. Therefore, we have decided to test whether the overexpression of this factor alone could increase gametocyte production and enable the investigation of uncharacterised, earliest stages of gametocyte development. To this end, we have engineered PBGAMi - a Plasmodium berghei line, in which all parasites were ap2-g deficient by default but able to overexpress it when induced with rapamycin. While the control parasites (PBGAMi R-), as expected, differentiated into asexual forms (schizonts) only, almost all rapamycin-treated parasites (PBGAMi R+) transformed into gametocytes. We used the generated line to perform RNA-seq analysis of the R- and R+ populations at different time points of their development and identify the changes arising between them, mapping the sequence of events leading to the formation of gametocytes.
2018-06-30 | GSE110201 | GEO
Project description:During the malaria infection, Plasmodium parasites invade the host’s red blood cells where they can differentiate into two different life forms. The majority will replicate asexually and infect new erythrocytes. A small percentage, however, will transform into gametocytes – a specialized sexual stage able to survive and develop when taken up by Anopheles mosquito. As the gametocytes ensure the parasite’s transmission to a new host, their generation is an attractive target for new antimalarial interventions. The molecular mechanisms controlling gametocytogenesis, however, remain largely unknown due to the technical challenges: the early gametocytes are morphologically indistinguishable from asexual parasites and present in very low numbers during the infection. Recently, AP2-G - a transcription factor from an apicomplexa-specific apiAP2 family – was described as indispensable for gametocyte commitment in both human malaria parasite Plasmodium falciparum and rodent malaria model Plasmodium berghei. Therefore, we have decided to test whether the overexpression of this factor alone could increase gametocyte production and enable the investigation of uncharacterised, earliest stages of gametocyte development. To this end, we have engineered PBGAMi - a Plasmodium berghei line, in which all parasites were ap2-g deficient by default but able to overexpress it when induced with rapamycin. While the control parasites (PBGAMi R-), as expected, differentiated into asexual forms (schizonts) only, almost all rapamycin-treated parasites (PBGAMi R+) transformed into gametocytes. We used the generated line to perform RNA-seq analysis of the R- and R+ populations at different time points of their development and identify the changes arising between them, mapping the sequence of events leading to the formation of gametocytes. At the same time we have generated purified transcriptomes of male and female gametocytes for the reference
2021-03-13 | GSE168817 | GEO
Project description:The purpose of this research is to identify and evaluate the global gene expression of the rodent malaria parasites Plasmodium yoelii, Plasmodium berghei and Plasmodium chabaudi blood-stage parasites and specifically compare the blood stage gene expression profiles of samples derived from previous studies on Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi
2016-04-08 | GSE80015 | GEO