PFNF54-Pfs16-GFP-LUC gametocytes treated at early stage or late stage development with compound MMV666810 or MMV674850
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ABSTRACT:
PROVIDER: PRJNA702816 | ENA |
REPOSITORIES: ENA
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Project description:Plasmodium falciparum gametocytes can often show differential drug responses depending on their stage of development. Here, the transcriptomic response of early stage (Stage II-III) and late stage (Stage IV-V) gametocytes was evaluated following treatment with chemical compounds that show differential killing activity between early and late-stage gametocytes.
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2018-04-30 | GSE104889 | GEO
Project description:PFNF54-Pfs16-GFP-LUC gametocyte time course from commitment to maturity
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Project description:Plasmodium falciparum parasites alternate between two different obligate hosts during their life cycle: humans and Anopheles mosquitoes. During the blood stage in the human host they proliferate asexually inside erythrocytes. A small proportion of parasites develops into male and female gametocytes, which enter the sexual part of the life cycle once taken up by a mosquito. The production of male and female gametocytes is therefore critical for malaria transmission. It has been shown that epigenetic processes play a role in this differentiation processes, however, the exact mechanisms remain unknown. To gain insight into these processes, we separated male and female gametocytes, based on the female specific expression of an endogenously GFP-tagged ABCG2 gene, using flow cytometry (male parasites as GFP low, female parasites as GFP high population). We subsequently performed ChIP-Seq for several histone variants and modifications (H2A.Z, H2A.Zac, H2B.Z, H3K4me3, H3R17me2, H3K27ac, H3K9me3) on day 6 of gametocytogenesis. Our study reveals a global remodelling of the chromatin landscape in gametocytes compared to asexual parasites, as well as sex specific differences.
2022-05-07 | GSE202214 | GEO
Project description:The ability of Plasmodium falciparum gametocytes to remain quiescent within the vertebrate host but poised for rapid onward development in the mosquito is an adaptation essential to maximise the onward spread of malaria. In this dormant state, mature infectious stage V gametocytes are largely unaffected by most antimalarial drugs and our limited understanding of how gametocytes prepare for mosquito transmission has hindered the identification of new molecular targets for transmission-blocking therapeutics. In this study, we move beyond the total proteome of gametocytes and define the translatome of mature stage V gametocytes using L-azidohomoalanine incorporation into nascent proteins, click chemistry purification and proteomic analysis. We identify the proteins and pathways that gametocytes sustain in preparation for transmission during this dormant period and through genetic disruption, we validate this approach by demonstrating the importance of parasite pyridoxal 5’-phosphate biosynthesis for mosquito transmission.
2026-03-25 | PXD075878 | Pride
Project description:The sexual stages are vital phases in malaria parasite transmission and are the targets of various interventions such as transmission blocking vaccines. The molecular mechanisms underlying sexual development, however, remain poorly understood. We report mappping of a determinant previously linked to a male gametocyte development defect in the P. falciparum Dd2 parasite to an 82 kb region on chromosome 12. In order to find a critical gene in this region, we compared gene expression pattern in sexual stage of the parasite between Dd2 and its normal gametocyte-producing ancestor W2 clones. The region contains a sexual stage specific gene (pfmdv 1) that is expressed substantially at a lower level in the Dd2 than in W2 parasite. Disruption of pfmdv 1 results in a dramatic reduction in mature gametocytes, especially male gametocytes, with the majority of sexually committed parasites arrested at stage-I. The pfmdv-1 knockout parasites show an enlarged nucleus, often with separation of the inner and outer nuclear membranes and presence of multi-membrane vesicles in red blood cell cytoplasm. Mosquito infectivity of the knockout parasites is also greatly reduced, but not completely lost, suggesting presence of compensatory mechanisms in the sexual development pathways. Data include Day 8 gametocytes of male defective Dd2 and parental W2 clones of Plasmodium falciparum. The series includes three biological repeats. Keywords: repeat sample
2010-06-10 | E-GEOD-2265 | biostudies-arrayexpress
Project description:In the human host, Plasmodium falciparum parasites propagate asexually in erythrocytes causing the symptoms of malaria. However, in every asexual cycle, a small proportion of the parasites commits to sexual differentiation, which is critical for transmission. During a period of about 10 days, the sexually committed parasites either develop into male or female gametocytes. In this study, gametocytes carrying an endogenously GFP tagged version of the female specifically expressed ABCG2 gene were FACS sorted to separate male (GFP low) and female (GFP high) gametocyte populations at different days of development. RNA was subsequently extracted from these populations as well as from asexual parasites as controls and subjected to directional RNAseq. These data reveal the transcriptional differences between asexual parasite stages and developing gametocytes, but also between male and female gametocytes as well as for each sex during the course of differentiation. In particular, male gametocytes undergo distinct transcriptional transitions when comparing the transcriptome between day 4, 6 and 10 of gametocytogenesis. In contrast, female gametocyte transcriptomes are more static during the course of gametocytogenesis and only show minimal variation. This is the first study to longitudinally monitor gene expression in developing male and female gametocytes
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Project description:Plasmodium berghei transcriptome for female gametocytes, male gametocytes, and asexual erythrocytic stages
2017-08-21 | GSE102167 | GEO
Project description:Investigation of whole genome gene expression level in Plasmodium falciparum male and female mature gametocytes, and detection of any transcriptional differences between male and female gametocytes. The Plasmodium falciparum parasite with green fluorescent protein (GFP) expression under the control of alpha tubulin II promoter facilitated the separation of male and female gametocyte. This engineered parasite strain in this study are further described in Miao J, Fan Q, Parker D, Li X, Li J, et al. (2013) Puf Mediates Translation Repression of Transmission-Blocking Vaccine Candidates in Malaria Parasites. PLoS Pathog 9(4): e1003268. doi: 10.1371/journal.ppat.1003268
2016-01-28 | GSE77316 | GEO
Project description:The sexual stages are vital phases in malaria parasite transmission and are the targets of various interventions such as transmission blocking vaccines. The molecular mechanisms underlying sexual development, however, remain poorly understood. We report mappping of a determinant previously linked to a male gametocyte development defect in the P. falciparum Dd2 parasite to an 82 kb region on chromosome 12. In order to find a critical gene in this region, we compared gene expression pattern in sexual stage of the parasite between Dd2 and its normal gametocyte-producing ancestor W2 clones. The region contains a sexual stage specific gene (pfmdv 1) that is expressed substantially at a lower level in the Dd2 than in W2 parasite. Disruption of pfmdv 1 results in a dramatic reduction in mature gametocytes, especially male gametocytes, with the majority of sexually committed parasites arrested at stage-I. The pfmdv-1 knockout parasites show an enlarged nucleus, often with separation of the inner and outer nuclear membranes and presence of multi-membrane vesicles in red blood cell cytoplasm. Mosquito infectivity of the knockout parasites is also greatly reduced, but not completely lost, suggesting presence of compensatory mechanisms in the sexual development pathways. Data include Day 8 gametocytes of male defective Dd2 and parental W2 clones of Plasmodium falciparum. The series includes three biological repeats. Keywords: repeat sample
2005-05-01 | GSE2265 | GEO