Russell, A. J. C. et al. (2023) Regulators of male and female sexual development are critical for the transmission of a malaria parasite. Cell Host and Microbe, 31(2), 305-319.e10. (doi: 10.1016/j.chom.2022.12.011) (PMID:36634679)
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Abstract
Malaria transmission to mosquitoes requires a developmental switch in asexually dividing blood-stage parasites to sexual reproduction. In Plasmodium berghei, the transcription factor AP2-G is required and sufficient for this switch, but how a particular sex is determined in a haploid parasite remains unknown. Using a global screen of barcoded mutants, we here identify genes essential for the formation of either male or female sexual forms and validate their importance for transmission. High-resolution single-cell transcriptomics of ten mutant parasites portrays the developmental bifurcation and reveals a regulatory cascade of putative gene functions in the determination and subsequent differentiation of each sex. A male-determining gene with a LOTUS/OST-HTH domain as well as the protein interactors of a female-determining zinc-finger protein indicate that germ-granule-like ribonucleoprotein complexes complement transcriptional processes in the regulation of both male and female development of a malaria parasite.
| Item Type: | Articles |
|---|---|
| Additional Information: | Funding: the work at the Wellcome Sanger Institute was funded by Wellcome core grant 206194/Z/17/Z awarded to O.B., M.K.N.L. and A.J.C.R. Work at Umeå University received funding from the Knut and Alice Wallenberg Foundation and the European Research Council (grant agreement no. 788516). Work at the University of Glasgow (A.P.W., A.B.R., and R.S.K.) was funded by the Wellcome Trust (refs: 083811, 104111, and 107046 to A.P.W.) and the BBSRC (ref BB/J013854/1 to R.S.K.). R.S.K. is supported by BBSRC (ref BB/J013854/1). K.K.M. is supported by the Wellcome Trust and Royal Society (202600/Z/16/Z). M.H. is supported by SNSF (P2SKP3_187635), HFSP (LT000131/2020-L), and a Marie Sklodowska-Curie Action fellowship (no. 895744). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Roberts, Dr Brett and Martin, Dr Julie and Waters, Professor Andy and Modrzynska, Dr Katarzyna |
| Authors: | Russell, A. J. C., Sanderson, T., Bushell, E., Talman, A. M., Anar, B., Girling, G., Hunziker, M., Kent, R. S., Martin, J. S., Metcalf, T., Montandon, R., Pandey, V., Pardo, M., Roberts, A. B., Sayers, C., Schwach, F., Choudhary, J. S., Rayner, J. C., Voet, T., Modrzynska, K. K., Waters, A. P., Lawniczak, M. K. N., and Billker, O. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Cell Host and Microbe |
| Publisher: | Elsevier (Cell Press) |
| ISSN: | 1931-3128 |
| ISSN (Online): | 1934-6069 |
| Published Online: | 11 January 2023 |
| Copyright Holders: | Copyright © 2023 The Authors |
| First Published: | First published in Cell Host and Microbe 31(2): 305-319.e10 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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