ORCID Profile
0000-0001-7419-0810
Current Organisation
Swiss Tropical and Public Health Institute
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Publisher: American Association for the Advancement of Science (AAAS)
Date: 16-03-2018
Abstract: Malaria-causing parasites ( Plasmodium ) have complex life histories in the tissues of humans. For the most part, the parasites focus their efforts on replication within the human host cells. However, occasionally, some replicating cells release gametes into the bloodstream, which are picked up by biting mosquitoes. Filarsky et al. discovered that the Plasmodium parasite keeps the production of gametes under tight epigenetic control using heterochromatin protein 1 (HP1). Plasmodium gametocytogenesis is initiated when HP1 is evicted from upstream of gamete-specific genes by gametocyte development 1 (GDV1) protein. GDV1 is in turn regulated by its antisense RNA. What triggers GDV1 expression remains unclear. Elucidating this pathway could provide a target for interrupting malaria transmission. Science , this issue p. 1259
Publisher: Springer Science and Business Media LLC
Date: 10-08-2021
DOI: 10.1038/S41467-021-24954-4
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 h ered 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.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Cold Spring Harbor Laboratory
Date: 06-11-2020
DOI: 10.1101/2020.11.06.370338
Abstract: Malaria parasites undergo a highly complex life cycle in the human host and the mosquito vector. The ApiAP2 family of sequence-specific DNA-binding proteins plays a dominant role in parasite development and life cycle progression. Of the ApiAP2 factors studied to date, most act as transcription factors regulating stage-specific gene expression. Here, we characterised a new ApiAP2 factor in Plasmodium falciparum (PF3D7_1456000) that we termed PfAP2-HC. Via detailed investigation of several single or double genetically engineered parasite lines, we demonstrate that PfAP2-HC specifically binds to heterochromatin throughout the genome. Intriguingly, PfAP2-HC does not bind DNA in vivo and recruitment of PfAP2-HC to heterochromatin is independent of its DNA-binding domain but strictly dependent on heterochromatin protein 1. Furthermore, our results suggest that PfAP2-HC functions neither in the regulation of gene expression nor in heterochromatin formation or maintenance. In summary, our findings reveal that PfAP2-HC constitutes a core component of heterochromatin in malaria parasites. They furthermore identify unexpected properties of ApiAP2 factors and suggest substantial functional ergence among the members of this important family of regulatory proteins.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Eilidh Carrington.