Regulators of male and female sexual development are critical for the transmission of a malaria parasite

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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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).
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 (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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
143385Conditional translational repression: a core regulatory mechanism of gene expression during development of the malaria parasite.Andrew WatersWellcome Trust (WELLCOTR)083811/Z/07/ZIII - Parasitology
170547The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/ZIII - Parasitology
172459Gene expression in Plasmodium parasites: the molecular mechanics of gametocytogenesis (and variant transcription of genes)Andrew WatersWellcome Trust (WELLCOTR)107046/Z/15/ZIII - Parasitology
190659BBSRC Doctoral Training Partnership 2012Jeremy MottramBiotechnology and Biological Sciences Research Council (BBSRC)BB/J013854/1MVLS - Graduate School