Regulators of sexual commitment in Plasmodium falciparum
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA666191 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12734245_1.fastq.gz | Fastqsanger.gz | |||
| SRR12734245_2.fastq.gz | Fastqsanger.gz | |||
| SRR12734246_1.fastq.gz | Fastqsanger.gz | |||
| SRR12734246_2.fastq.gz | Fastqsanger.gz | |||
| SRR12734247_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:The aim of this study was to identify transcriptonal responses during sexual commitment of P. falciparum mutants unable to form gametocytes.
2020-09-29 | GSE158689 | GEO
Project description:For malaria transmission, the parasite must undergo sexual differentiation into mature gametocytes. However, the molecular basis for this critical transition in the parasites life cycle is unknown. Six previously uncharacterized genes, Pfg14.744, Pfg14.745, Pfg14.748, Pfg14.763, Pfg14.752 and Pfg6.6 that are members of a 36 gene Plasmodium falciparum-specific subtelomeric superfamily were found to be expressed in parasites that are committed to sexual development as suggested by co-expression of Pfs16 and Pfg27. Northern blots demonstrated that Pfg14.744 and Pfg14.748 were first expressed before the parasites differentiated into morphologically distinct gametocytes, transcription continued to increase until stage II gametocytes were formed and then rapidly decreased. Immunofluorescence assays indicated that both proteins were only produced in the subpopulation of ring stage parasites that are committed to gametocytogenesis and both localized to the parasitophorous vacuole (PV)b of the early ring stage parasites. As the parasites continued to develop Pfg14.748 remained within the parasitophorous vacuole, while Pfg14.744 was detected in the erythrocyte. The 5' flanking region of either gene alone was sufficient to drive early gametocyte specific expression of green fluorescent protein (GFP). In parasites transfected with a plasmid containing the Pfg14.748 5' flanking region immediately upstream of GFP, fluorescence was observed in a small number of schizonts the cycle before stage I gametocytes were observed. This expression pattern is consistent with commitment to sexual differentiation prior to merozoite release and erythrocyte invasion. Further investigation into the role of these genes in the transition from asexual to sexual differentiation could provide new strategies to block malaria transmission. Microarray analysis was used to compare two clones derived from Plasmodium falciparum strain 3D7 parasites that differ in their ability to undergo gametocytogenesis. Clone G+ produces gametocytes and clone G- produces very few if any gametocytes. RNA was harvested from the cultures when the asexual parasitemia was 0.9-1.48% (day 4) (n=4) after setting up the gametocyte cultures and 5.2-5.58% (day 6) (n=4) prior to the appearance of morphologically distinct gametocytes and used to generate cDNA that was labeled with Cy3 or Cy5 and hybridized to the Plasmodium falciparum 70 mer oligonucleotide microarray developed by DeRisi and co-workers.
2014-10-16 | E-GEOD-62364 | biostudies-arrayexpress
Project description:During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes – sexual stage precursor cells – likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the blood stream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood. We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and ~30 hours post invasion and mature gametocytes after around 7 days post invasion.
2015-01-13 | GSE64887 | GEO
Project description:During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes M-bM-^@M-^S sexual stage precursor cells M-bM-^@M-^S likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the blood stream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood. We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and ~30 hours post invasion and mature gametocytes after around 7 days post invasion. We used 164/TdTom, a transgenic parasite line expressing a red fluorescent protein reporter under a gametocyte-specific promoter to generate schizont samples. Schizonts were subsequently isolated from both the fluorescent and non-fluorescent population by FACS and prepared for microarray analysis. Two biological replicates were produced for both the fluorescent and the non-fluorescent samples.
2015-01-13 | E-GEOD-64887 | 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:Investigation of whole genome gene expression level changes in Plasmodium falciparum 3D7 delta-PfPuf2 mutant, compared to the wild-type strain 3D7. The mutation engineered into this strain render tanslational control. The mutants analyzed in this study are further described in Miao J, Li J, Fan Q, Li X, Li X, Cui L.2010. The Puf-family RNA-binding protein PfPuf2 regulates sexual development and sex differentiation in the malaria parasite Plasmodium falciparum. J Cell Sci. 123(7):1039-49 (PMID 20197405). A 12 chip study using total RNA recovered from six separate wild-type cultures of Plasmodium falciparum 3D7 at gametocyte stage III (three cultures) and stage V (three cultures) and six separate cultures of dalta PfPuf2 mutant at gametocyte stage III (three cultures) and stage V (three cultures). Each chip measures the expression level of 5,367 genes from Plasmodium falciparum 3D7 with 45-60 mer probes with two replicates on final array of 71618 probes.
2012-07-05 | E-GEOD-39124 | biostudies-arrayexpress
Project description:Investigation of whole genome gene expression level changes in Plasmodium falciparum 3D7 delta-PfPuf2 mutant, compared to the wild-type strain 3D7. The mutation engineered into this strain render tanslational control. The mutants analyzed in this study are further described in Miao J, Li J, Fan Q, Li X, Li X, Cui L.2010. The Puf-family RNA-binding protein PfPuf2 regulates sexual development and sex differentiation in the malaria parasite Plasmodium falciparum. J Cell Sci. 123(7):1039-49 (PMID 20197405).
2012-07-06 | GSE39124 | GEO
Project description:Purpose: The goal of this study was to identify genes associated with increased sexual differentiation in P. falciparum. Method: RNAseq analysis of two different P. falciparum strains (NF54 and Pf2004/164tdTom) cultured under sexual differentiation-inducing (-SerM) and non-inducing (-SerM/LysoPC and -SerM/Serum) conditions Results: We found a total of 342 genes significantly induced in response to LysoPC depletion, thereby determining changes associated with sexual differentiation and limiting Kenndedy pathway substrates.
2017-11-16 | GSE104114 | GEO
Project description:The project examined the function of the putative transcription factor PfAP2-O from Plasmodium falciparum. This factor besides an essential function in sexual stages also influences variant, virulence associated genes. In a pull down analysis, HA-tagged PfAP2-O was immunoprecipitated and proteins assoaciated were analysed and three differentially appearing protein bands were analysed.
2021-06-28 | PXD026237 | Pride
Project description:In the malaria parasite Plasmodium falciparum, changes in the distribution of heterochromatin at specific loci regulate the expression of clonally variant genes (CVGs), which play fundamental roles in host-parasite interactions. In addition to differences in heterochromatin between individual parasites associated with variant expression of CVGs, changes in heterochromatin distribution associated with different developmental stages have been described. However, while stage II/III gametocytes (sexual precursors) have an altered distribution of heterochromatin compared with asexual blood stages, it is unclear if heterochromatin changes already occur at the very early stages of sexual development. Here we used a transgenic parasite line in which sexual conversion can be conditionally induced to characterise the changes in heterochromatin distribution associated with the earliest stages of sexual development. We found that there were essentially no changes in sexual rings or stage I gametocytes compared with asexual blood stages, and remodelling of heterochromatin started at stage II or III of gametocyte development, with changes similar to those previously described in parasites of a different genetic background. Therefore, global redistribution of heterochromatin does not appear to play a role in the initial steps of sexual development. We also found that, for several genes, changes in expression associated with sexual development precede changes in the heterochromatin at their locus.
2024-10-09 | GSE252334 | GEO