Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-24954-4
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Funding
- Swiss National Science Foundation [BSCGI0_157729, 31003A_169347]
- Fondation Pasteur Suisse
- Jurgen Manchot Foundation
- European Union's Horizon 2020 research and innovation programme [733273]
- Netherlands Organisation for Scientific Research [NWO-VIDI 864.13.009]
- Swiss National Science Foundation (SNF) [BSCGI0_157729, 31003A_169347] Funding Source: Swiss National Science Foundation (SNF)
- H2020 Societal Challenges Programme [733273] Funding Source: H2020 Societal Challenges Programme
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Researchers have successfully engineered P. falciparum parasites using genome editing tools to achieve higher sexual commitment rates, providing a new approach for studying gametocyte biology. By introducing inducible gametocyte producer lines, they have successfully achieved large-scale, synchronized gametocyte production, providing valuable resources for research on the transmission stage of malaria parasites.
During each replication cycle of P. falciparum in the human bloodstream, a small proportion of parasites commits to sexual development and differentiates into transmission-relevant gametocytes. Applying CRISPR-based genome editing, Boltryk et al. engineer P. falciparum lines with sexual commitment rates of 75% to promote future studies on gametocyte biology. 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.
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