PFNF54-Pfs16-GFP-LUC gametocyte time course from commitment to maturity
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ABSTRACT:
ORGANISM(S): Plasmodium falciparum
PROVIDER: GSE104889 | GEO | 2018/04/30
REPOSITORIES: GEO
Similar Datasets
Project description:PFNF54-Pfs16-GFP-LUC gametocyte time course from commitment to maturity
| PRJNA414097 | ENA
Project description:The Plasmodium sexual gametocyte stages are the only transmissible form of the malaria parasite and are thus responsible for the continued transmission of the disease. Gametocytes undergo extensive functional and morphological changes from commitment to maturity, directed by an equally extensive control program. Several interconnected mechanisms governing sexual commitment have been described. However, the processes that drive the subsequent differentiation and development of the gametocyte remain largely unexplored. Using chromatin immunoprecipitation followed by high-throughput sequencing we map the genome-wide occupancy of H3K36me2 and H3K36me3 during early gametocyte development and describe an association between these histone modifications and the global changes in the transcriptional program driving gametocyte development post-commitment.
2021-04-20 | GSE163432 | GEO
Project description:Malaria is spread by the transmission of sexual stage parasites, called gametocytes. However, with Plasmodium falciparum, gametocytes can only be detected in peripheral blood when they are mature and transmissible to a mosquito, which complicates control efforts. Here, we identify the set of genes overexpressed in patient blood samples with high levels of gametocyte-committed ring stage parasites. Expression of all 18 genes was regulated by transcription factor AP2-G, which is required for gametocytogenesis. We selected three genes, not expressed in mature gametocytes, to develop as biomarkers. All three biomarkers were validated in vitro using 6 different parasite lines and an algorithm developed that predicted gametocyte production in ex vivo samples and volunteer infection studies. The biomarkers were also sensitive enough to monitor gametocyte production in asymptomatic P. falciparum carriers allowing early detection and treatment of infectious reservoirs, as well as the in vivo analysis of factors that modulate sexual conversion.
2020-09-25 | GSE152536 | GEO
Project description:We described the biological role of a putative zinc finger protein (Plasmodb id: PF3D7_1008600), which plays an important role during the initiation and subsequent progression of gametocytogenesis in P. falciparum. Hence we termed the protein P. falciparum Zinc Finger Protein for Gametocytogenesis (PfZnFP-G). During the asexual intraerythrocyic developmental cycle (IDC), PfZnFP-G levels peak during the schizont stage during which it is localized in the nucleus. During the IDC, PfZnFP-G appears to be stochastically expressed in ~3% parasite population. Deactivation of PfZnFP-G appears to suppress, but not fully inhibit, production of gametocytes and vice versa overproduction of PfZnFP-G stimulates gametocytogenesis. In addition, PfZnFP-G is capable of associating with DNA binding preferentially to intergenic, promoter regions of the genome, and this binding correlates positively with transcription, particularly of other gametocyte specific genes. PfZnFP-G is also expressed in the mid-to-late gametocytes where it is present in the cytoplasm. Overall, these results suggest a dual function of PfZnFP-G in gametocytogenesis including: (i) commitment as a transcription factor and (ii) gametocyte maturation as a putative RNA binding protein. Transgenic 3D7 wild type parasite lines were generated with PfZnFP-G tagged, over-expressed and knocked-out. Transcriptional profiles across the parasite life cycle were generated. Genome occupancy of PfZnFP-G were also investigated and compared to the corresponding transcriptional profiles.
2015-11-24 | E-GEOD-75295 | biostudies-arrayexpress
Project description:A genome-wide expression analysis was undertaken to identify novel genes specifically activated from early stages of gametocytogenesis in Plasmodium falciparum. A comparative analysis was conducted on sexually induced cultures of reference parasite clone 3D7 and its gametocyteless derivative clone F12. Competitive hybridisations on long-oligomer microarrays representing 4488 P. falciparum genes identified a remarkably small number of transcripts differentially produced in the two clones. Upregulation of the mRNAs for the early gametocyte markers Pfs16 and Pfg27 was however readily detected in 3D7, and such genes were used as reference transcripts in a comparative time course analysis of 3D7 and F12 parasites between 30 and 40 h post-invasion in cultures induced to enter gametocytogenesis. One hundred and seventeen genes had expression profiles which correlated to those of pfs16 and pfg27, and Northern blot analysis and published proteomic data identified those whose expression was gametocyte-specific. Immunofluorescence analysis with antibodies against two of these gene products identified two novel parasite membrane associated, sexual stage-specific proteins. One was produced from stage I gametocytes and the second showed peak production in stage II gametocytes. The two proteins were named Pfpeg-3 and Pfpeg-4, for P. falciparum proteins of early gametocytes.
2007-09-26 | E-MEXP-1250 | biostudies-arrayexpress
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:The P.falciparum gametocyte proteomes of wild type gametocytes and two clones of Pfg377 depleted gametocytes were obtained for a label free comparative analysis to identify osmiophilic body proteins. Gametocyte samples were analyzed by LC-MS/MS and processed by MaxQuant for identification and LFQ quantification.
2016-07-21 | PXD004124 | Pride
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
2021-07-31 | GSE180985 | GEO
Project description:We described the biological role of a putative zinc finger protein (Plasmodb id: PF3D7_1008600), which plays an important role during the initiation and subsequent progression of gametocytogenesis in P. falciparum. Hence we termed the protein P. falciparum Zinc Finger Protein for Gametocytogenesis (PfZnFP-G). During the asexual intraerythrocyic developmental cycle (IDC), PfZnFP-G levels peak during the schizont stage during which it is localized in the nucleus. During the IDC, PfZnFP-G appears to be stochastically expressed in ~3% parasite population. Deactivation of PfZnFP-G appears to suppress, but not fully inhibit, production of gametocytes and vice versa overproduction of PfZnFP-G stimulates gametocytogenesis. In addition, PfZnFP-G is capable of associating with DNA binding preferentially to intergenic, promoter regions of the genome, and this binding correlates positively with transcription, particularly of other gametocyte specific genes. PfZnFP-G is also expressed in the mid-to-late gametocytes where it is present in the cytoplasm. Overall, these results suggest a dual function of PfZnFP-G in gametocytogenesis including: (i) commitment as a transcription factor and (ii) gametocyte maturation as a putative RNA binding protein.
2015-11-24 | GSE75295 | GEO
Project description:Differentiation from asexual blood stages to sexual gametocytes is required for transmission of malaria parasites from the human host to mosquitos, where sexual fertilization occurs to complete the lifecycle. Although preventing gametocyte development would block parasite transmission, the molecular mechanisms underlying sexual commitment and gametocyte maturation are still relatively unknown. Previous studies identified an ApiAP2 protein, AP2-G2, which plays a critical role in gametocyte maturation in rodent malaria parasite Plasmodium berghei by acting as the repressor of asexual stage genes in gametocytes. In this work we characterize the P. falciparum orthologue (PF3D7_1408200) of PbAP2-G2 and report that it plays a critical role in maturation of gametocytes. Disruption of pfap2-g2 did not obstruct commitment to sexual development but the majority of parasites were unable to develop normally beyond stage III gametocytes. In asexual stages PfAP2-G2 binds to the promoters of wide variety of genes expressed in diverse range of parasite’s life cycle stages including gametocytes, mosquito lifecycle stages early ring stage genes and genes encoding for proteins involved in egress and invasion. Surprisingly, we also identify binding of PfAP2-G2 in the gene body of almost 3000 genes. We could also show that PfAP2-G2 interacts with chromatin remodeling proteins and another ApiAP2 protein (PF3D7_1139300) whose motif is also overrepresented in the ChIP-seq data. Overall this work suggests that PfAP2-G2 is a transcriptional regulator that regulates genes possibly by recruiting additional transcription factors and chromatin remodeling machinery and plays a critical role in the development of malaria parasites as they transition from the asexual stage to gametocytes.
2021-02-16 | GSE157753 | GEO