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The PfRCR complex bridges malaria parasite and erythrocyte during invasion (2023)
Journal Article
Farrell, B., Alam, N., Hart, M. N., Jamwal, A., Ragotte, R. J., Walters-Morgan, H., …Higgins, M. K. (2023). The PfRCR complex bridges malaria parasite and erythrocyte during invasion. Nature, https://doi.org/10.1038/s41586-023-06856-1

The symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex1, containing PfRH5 (refs. 2,3), PfCyRPA, PfRIPR, PfCSS and PfPTRAMP, is essential for erythrocyte in... Read More about The PfRCR complex bridges malaria parasite and erythrocyte during invasion.

DNA-binding protein PfAP2-P regulates parasite pathogenesis during malaria parasite blood stages (2023)
Journal Article
Subudhi, A. K., Green, J. L., Satyam, R., Salunke, R. P., Lenz, T., Shuaib, M., …Pain, A. (2023). DNA-binding protein PfAP2-P regulates parasite pathogenesis during malaria parasite blood stages. Nature Microbiology, 8(11), 2154-2169. https://doi.org/10.1038/s41564-023-01497-6

Malaria-associated pathogenesis such as parasite invasion, egress, host cell remodelling and antigenic variation requires concerted action by many proteins, but the molecular regulation is poorly understood. Here we have characterized an essential Pl... Read More about DNA-binding protein PfAP2-P regulates parasite pathogenesis during malaria parasite blood stages.

Sequential roles for red blood cell binding proteins enable phased commitment to invasion for malaria parasites (2023)
Journal Article
Hart, M. N., Mohring, F., DonVito, S. M., Thomas, J. A., Muller-Sienerth, N., Wright, G. J., …Moon, R. W. (in press). Sequential roles for red blood cell binding proteins enable phased commitment to invasion for malaria parasites. Nature Communications, 14(1), 4619. https://doi.org/10.1038/s41467-023-40357-z

Invasion of red blood cells (RBCs) by Plasmodium merozoites is critical to their continued survival within the host. Two major protein families, the Duffy binding-like proteins (DBPs/EBAs) and the reticulocyte binding like proteins (RBLs/RHs) have be... Read More about Sequential roles for red blood cell binding proteins enable phased commitment to invasion for malaria parasites.

Characterisation of the bovine C-type lectin receptor Mincle and potential evidence for an endogenous ligand (2023)
Journal Article
Holder, A., Kolakowski, J., Rosentreter, C., Knuepfer, E., Jegouzo, S., Rosenwasser, O., …Werling, D. (2023). Characterisation of the bovine C-type lectin receptor Mincle and potential evidence for an endogenous ligand. Frontiers in Immunology, 14, https://doi.org/10.3389/fimmu.2023.1189587

Innate immune receptors that form complexes with secondary receptors, activating multiple signalling pathways, modulate cellular activation and play essential roles in regulating homeostasis and immunity. We have previously identified a variety of bo... Read More about Characterisation of the bovine C-type lectin receptor Mincle and potential evidence for an endogenous ligand.

Apicoplast ribosomal protein S10-V127M enhances artemisinin resistance of a Kelch13 transgenic Plasmodium falciparum (2022)
Journal Article
Kampoun, T., Srichairatanakool, S., Prommana, P., Shaw, P. J., Green, J. L., Knuepfer, E., …Uthaipibull, C. (in press). Apicoplast ribosomal protein S10-V127M enhances artemisinin resistance of a Kelch13 transgenic Plasmodium falciparum. Malaria Journal, 21(1), Article 302. https://doi.org/10.1186/s12936-022-04330-3

Background: The resistance of Plasmodium falciparum to artemisinin-based (ART) drugs, the front-line drug family used in artemisinin-based combination therapy (ACT) for treatment of malaria, is of great concern. Mutations in the kelch13 (k13) gene... Read More about Apicoplast ribosomal protein S10-V127M enhances artemisinin resistance of a Kelch13 transgenic Plasmodium falciparum.

Genetic disruption of Plasmodium falciparum Merozoite surface antigen 180 (PfMSA180) suggests an essential role during parasite egress from erythrocytes (2021)
Journal Article
Bahl, V., Chaddha, K., Mian, S., Holder, A., Knuepfer, E., & Gaur, D. (2021). Genetic disruption of Plasmodium falciparum Merozoite surface antigen 180 (PfMSA180) suggests an essential role during parasite egress from erythrocytes. Scientific Reports, 11(1), https://doi.org/10.1038/s41598-021-98707-0

Plasmodium falciparum, the parasite responsible for severe malaria, develops within erythrocytes. Merozoite invasion and subsequent egress of intraerythrocytic parasites are essential for this erythrocytic cycle, parasite survival and pathogenesis. I... Read More about Genetic disruption of Plasmodium falciparum Merozoite surface antigen 180 (PfMSA180) suggests an essential role during parasite egress from erythrocytes.

Autocatalytic activation of a malarial egress protease is druggable and requires a protein cofactor (2021)
Journal Article
Tan, M., Koussis, K., Withers-Martinez, C., Howell, S., Thomas, J., Hackett, F., …Blackman, M. (2021). Autocatalytic activation of a malarial egress protease is druggable and requires a protein cofactor. EMBO Journal, 40(11), https://doi.org/10.15252/embj.2020107226

Malaria parasite egress from host erythrocytes (RBCs) is regulated by discharge of a parasite serine protease called SUB1 into the parasitophorous vacuole (PV). There, SUB1 activates a PV-resident cysteine protease called SERA6, enabling host RBC rup... Read More about Autocatalytic activation of a malarial egress protease is druggable and requires a protein cofactor.

Inhibition of protein N-myristoylation blocks Plasmodium falciparum intraerythrocytic development, egress and invasion (2021)
Journal Article
Schlott, A., Knuepfer, E., Green, J., Hobson, P., Borg, A., Morales-Sanfrutos, J., …Holder, A. (2021). Inhibition of protein N-myristoylation blocks Plasmodium falciparum intraerythrocytic development, egress and invasion. PLoS Biology, 19(10), https://doi.org/10.1371/journal.pbio.3001408

We have combined chemical biology and genetic modification approaches to investigate the importance of protein myristoylation in the human malaria parasite, Plasmodium falciparum. Parasite treatment during schizogony in the last 10 to 15 hours of the... Read More about Inhibition of protein N-myristoylation blocks Plasmodium falciparum intraerythrocytic development, egress and invasion.

Deletion of Plasmodium falciparum ubc13 increases parasite sensitivity to the mutagen, methyl methanesulfonate and dihydroartemisinin (2021)
Journal Article
Maneekesorn, S., Knuepfer, E., Green, J. L., Prommana, P., Uthaipibull, C., Srichairatanakool, S., & Holder, A. A. (in press). Deletion of Plasmodium falciparum ubc13 increases parasite sensitivity to the mutagen, methyl methanesulfonate and dihydroartemisinin. Scientific Reports, 11(1), Article 21791. https://doi.org/10.1038/s41598-021-01267-6

The inducible Di-Cre system was used to delete the putative ubiquitin-conjugating enzyme 13 gene (ubc13) of Plasmodium falciparum to study its role in ubiquitylation and the functional consequence during the parasite asexual blood stage. Deletion res... Read More about Deletion of Plasmodium falciparum ubc13 increases parasite sensitivity to the mutagen, methyl methanesulfonate and dihydroartemisinin.

Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites (2019)
Journal Article
Knuepfer, E., Wright, K. E., Prajapati, S. K., Rawlinson, T. A., Mohring, F., Koch, M., …Holder, A. A. (2019). Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites. PLoS Pathogens, 15(6), e1007809. https://doi.org/10.1371/journal.ppat.1007809

Malaria is caused by Plasmodium parasites, which invade and replicate in erythrocytes. For Plasmodium falciparum, the major cause of severe malaria in humans, a heterotrimeric complex comprised of the secreted parasite proteins, PfCyRPA, PfRIPR and P... Read More about Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites.