Automated transcription profiling to monitor malaria parasite sexual differentiation

Author(s):  
Abel Cruz Camacho ◽  
Edo Kiper
Parasitology ◽  
2000 ◽  
Vol 121 (2) ◽  
pp. 127-133 ◽  
Author(s):  
T. G. SMITH ◽  
P. LOURENÇO ◽  
R. CARTER ◽  
D. WALLIKER ◽  
L. C. RANFORD-CARTWRIGHT

2019 ◽  
Author(s):  
Nanika Coetzee ◽  
Hilde von Grüning ◽  
Mariette van der Watt ◽  
Janette Reader ◽  
Lyn-Marié Birkholtz

AbstractThe epigenome of the malaria parasite, Plasmodium falciparum, is associated with control of various essential processes in the parasite including control of proliferation of asexual development as well as sexual differentiation. The unusual nature of the epigenome has prompted investigations of the potential to target epigenetic modulators with novel chemotypes. Here, we explored the diversity associated with a library of 95 compounds, active against various epigenetic modifiers within cancerous cells, for activity against multiple stages of P. falciparum development. We show that P. falciparum is differentially susceptible to epigenetic perturbation during asexual and sexual development, with early stage gametocytes particularly sensitive to epi-drugs targeting both histone and non-histone epigenetic modifiers. Moreover, 4 compounds targeting histone acetylation and methylation, show potent multistage activity against asexual parasites, early and late stage gametocytes, with transmission-blocking potential. Overall, these results warrant further examination of the potential antimalarial properties of these hit compounds.


2019 ◽  
Author(s):  
Riëtte van Biljon ◽  
Roelof van Wyk ◽  
Heather J. Painter ◽  
Lindsey Orchard ◽  
Janette Reader ◽  
...  

AbstractMalaria pathogenesis relies on sexual gametocyte forms of the malaria parasite to be transmitted between the infected human and the mosquito host but the molecular mechanisms controlling gametocytogenesis remains poorly understood. Here we provide a high-resolution transcriptome ofPlasmodium falciparumas it commits to and develops through gametocytogenesis. The gametocyte-associated transcriptome is significantly different from that of the asexual parasites, with dynamic gene expression shifts characterizing early, intermediate and late-stage gametocyte development and results in differential timing for sex-specific transcripts. The striking transcriptional dynamics suggest strict transcriptional control during gametocytogenesis inP. falciparum, which we propose is mediated by putative regulators including epigenetic mechanisms (driving active repression of proliferation-associated processes) and a cascade-like expression of ApiAP2 transcription factors. The gametocyte transcriptome serves as the blueprint for sexual differentiation and will be a rich resource for future functional studies on this critical stage ofPlasmodiumdevelopment, as the intraerythrocytic transcriptome has been for our understanding of the asexual cycle.


Author(s):  
Riëtte van Biljon ◽  
Roelof van Wyk ◽  
Heather J. Painter ◽  
Lindsey Orchard ◽  
Janette Reader ◽  
...  

Abstract Background Malaria pathogenesis relies on sexual gametocyte forms of the malaria parasite to be transmitted between the infected human and the mosquito host but the molecular mechanisms controlling gametocytogenesis remains poorly understood. Here we provide a high-resolution transcriptome of Plasmodium falciparum as it commits to and develops through gametocytogenesis. Results The gametocyte-associated transcriptome is significantly different from that of the asexual parasites, with dynamic gene expression shifts characterizing early, intermediate and late-stage gametocyte development and results in differential timing for sex-specific transcripts. The transcriptional dynamics suggest strict transcriptional control during gametocytogenesis in P. falciparum, which we propose is mediated by putative regulators including epigenetic mechanisms (driving active repression of proliferation-associated processes) and a cascade-like expression of ApiAP2 transcription factors. Conclusions The gametocyte transcriptome serves as the blueprint for sexual differentiation and will be a rich resource for future functional studies on this critical stage of Plasmodium development, as the intraerythrocytic transcriptome has been for our understanding of the asexual cycle.


BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Riëtte van Biljon ◽  
Roelof van Wyk ◽  
Heather J. Painter ◽  
Lindsey Orchard ◽  
Janette Reader ◽  
...  

Abstract Background Malaria pathogenesis relies on sexual gametocyte forms of the malaria parasite to be transmitted between the infected human and the mosquito host but the molecular mechanisms controlling gametocytogenesis remains poorly understood. Here we provide a high-resolution transcriptome of Plasmodium falciparum as it commits to and develops through gametocytogenesis. Results The gametocyte-associated transcriptome is significantly different from that of the asexual parasites, with dynamic gene expression shifts characterizing early, intermediate and late-stage gametocyte development and results in differential timing for sex-specific transcripts. The transcriptional dynamics suggest strict transcriptional control during gametocytogenesis in P. falciparum, which we propose is mediated by putative regulators including epigenetic mechanisms (driving active repression of proliferation-associated processes) and a cascade-like expression of ApiAP2 transcription factors. Conclusions The gametocyte transcriptome serves as the blueprint for sexual differentiation and will be a rich resource for future functional studies on this critical stage of Plasmodium development, as the intraerythrocytic transcriptome has been for our understanding of the asexual cycle.


2019 ◽  
Author(s):  
Riëtte van Biljon ◽  
Roelof van Wyk ◽  
Heather J. Painter ◽  
Lindsey Orchard ◽  
Janette Reader ◽  
...  

Abstract Background: Malaria pathogenesis relies on sexual gametocyte forms of the malaria parasite to be transmitted between the infected human and the mosquito host but the molecular mechanisms controlling gametocytogenesis remains poorly understood. Here we provide a high-resolution transcriptome of Plasmodium falciparum as it commits to and develops through gametocytogenesis. Results : The gametocyte-associated transcriptome is significantly different from that of the asexual parasites, with dynamic gene expression shifts characterizing early, intermediate and late-stage gametocyte development and results in differential timing for sex-specific transcripts. The transcriptional dynamics suggest strict transcriptional control during gametocytogenesis in P. falciparum, which we propose is mediated by putative regulators including epigenetic mechanisms (driving active repression of proliferation-associated processes) and a cascade-like expression of ApiAP2 transcription factors. Conclusions : The gametocyte transcriptome serves as the blueprint for sexual differentiation and will be a rich resource for future functional studies on this critical stage of Plasmodium development, as the intraerythrocytic transcriptome has been for our understanding of the asexual cycle.


2019 ◽  
Author(s):  
Riëtte van Biljon ◽  
Roelof van Wyk ◽  
Heather J. Painter ◽  
Lindsey Orchard ◽  
Janette Reader ◽  
...  

Abstract Background: Malaria pathogenesis relies on sexual gametocyte forms of the malaria parasite to be transmitted between the infected human and the mosquito host but the molecular mechanisms controlling gametocytogenesis remains poorly understood. Here we provide a high-resolution transcriptome of Plasmodium falciparum as it commits to and develops through gametocytogenesis. Results : The gametocyte-associated transcriptome is significantly different from that of the asexual parasites, with dynamic gene expression shifts characterizing early, intermediate and late-stage gametocyte development and results in differential timing for sex-specific transcripts. The transcriptional dynamics suggest strict transcriptional control during gametocytogenesis in P. falciparum, which we propose is mediated by putative regulators including epigenetic mechanisms (driving active repression of proliferation-associated processes) and a cascade-like expression of ApiAP2 transcription factors. Conclusions : The gametocyte transcriptome serves as the blueprint for sexual differentiation and will be a rich resource for future functional studies on this critical stage of Plasmodium development, as the intraerythrocytic transcriptome has been for our understanding of the asexual cycle.


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