CRISPR/Cas9-engineered inducible gametocyte producer lines as a valuable tool for Plasmodium falciparum malaria transmission research.
Sylwia D. Boltryk,Sylwia D. Boltryk,Armin Passecker,Armin Passecker,Arne Alder,Arne Alder,Eilidh Carrington,Eilidh Carrington,Marga van de Vegte-Bolmer,Geert-Jan van Gemert,Alex van der Starre,Hans-Peter Beck,Hans-Peter Beck,Robert W. Sauerwein,Taco W. A. Kooij,Nicolas M. B. Brancucci,Nicolas M. B. Brancucci,Nicholas I Proellochs,Tim-Wolf Gilberger,Tim-Wolf Gilberger,Till S. Voss,Till S. Voss +21 more
TLDR
In this paper, P. falciparum NF54 inducible gametocyte producer (iGP) lines for the routine mass production of synchronous gametocytes via conditional overexpression of the sexual commitment factor GDV1.Abstract:
The malaria parasite Plasmodium falciparum replicates inside erythrocytes in the blood of infected humans. During each replication cycle, a small proportion of parasites commits to sexual development and differentiates into gametocytes, which are essential for parasite transmission via the mosquito vector. Detailed molecular investigation of gametocyte biology and transmission has been hampered by difficulties in generating large numbers of these highly specialised cells. Here, we engineer P. falciparum NF54 inducible gametocyte producer (iGP) lines for the routine mass production of synchronous gametocytes via conditional overexpression of the sexual commitment factor GDV1. NF54/iGP lines consistently achieve sexual commitment rates of 75% and produce viable gametocytes that are transmissible by mosquitoes. We also demonstrate that further genetic engineering of NF54/iGP parasites is a valuable tool for the targeted exploration of gametocyte biology. In summary, we believe the iGP approach developed here will greatly expedite basic and applied malaria transmission stage research.read more
Citations
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Expansion microscopy of Plasmodium gametocytes reveals the molecular architecture of a bipartite microtubule organisation centre coordinating mitosis with axoneme assembly
Ravish Rashpa,Meyliyev Sobir, Xamidullayeva Muxlisa, Samandarova Madina, Abdullayeva Durdona +1 more
TL;DR: In this article , the authors combined ultrastructure expansion microscopy (U-ExM) with bulk proteome labeling to reconstruct the subpellicular microtubule network which confers cell rigidity to Plasmodium falciparum gametocytes.
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Transmission-blocking drugs for malaria elimination.
TL;DR: In this article , the authors provide an updated roadmap to the discovery and development of new antimalarials with transmission-blocking activity to guide drug discovery for malaria elimination, which can reduce the risk of reinfection and also curb the spread of drug resistance.
Journal ArticleDOI
Repurposing the mitotic machinery to drive cellular elongation and chromatin reorganisation in Plasmodium falciparum gametocytes
TL;DR: In this article , a non-mitotic microtubule organizing center (MTOC) embedded in the parasite's nuclear membrane, orients the endoplasmic reticulum and the nascent IMC and seeds cytoplasmic microtubules.
Journal ArticleDOI
Revisiting the Effect of Pharmaceuticals on Transmission Stage Formation in the Malaria Parasite Plasmodium falciparum
TL;DR: In this paper , a P. falciparum reporter line was used to quantify sexual commitment rates after exposure to antimalarials and other pharmaceuticals commonly prescribed in malaria-endemic regions.
Posted ContentDOI
Revisiting the effect of pharmaceuticals on transmission stage formation in the malaria parasite Plasmodium falciparum
TL;DR: In this paper, a P. falciparum reporter line was used to quantify sexual commitment rates after exposure to antimalarials and other pharmaceuticals commonly prescribed in malaria-endemic regions.
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