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  1. Article ; Online: Plasmodium falciparum goes bananas for sex.

    Dixon, Matthew W A / Tilley, Leann

    Molecular and biochemical parasitology

    2021  Volume 244, Page(s) 111385

    Abstract: The sexual blood stages of the human malaria parasite Plasmodium falciparum undergo a remarkable transformation from a roughly spherical shape to an elongated crescent or "falciform" morphology from which the species gets its name. In this review, the ... ...

    Abstract The sexual blood stages of the human malaria parasite Plasmodium falciparum undergo a remarkable transformation from a roughly spherical shape to an elongated crescent or "falciform" morphology from which the species gets its name. In this review, the molecular events that drive this spectacular shape change are discussed and some questions that remain regarding the mechanistic underpinnings are posed. We speculate on the role of the shape changes in promoting sequestration and release of the developing gametocyte, thereby facilitating parasite survival in the host and underpinning transmission to the mosquito vector.
    MeSH term(s) Animals ; Biomechanical Phenomena ; Culicidae/parasitology ; Erythrocytes/parasitology ; Female ; Gametogenesis ; Hepatocytes/parasitology ; Host-Parasite Interactions/genetics ; Humans ; Insect Vectors/parasitology ; Life Cycle Stages/genetics ; Malaria, Falciparum/parasitology ; Malaria, Falciparum/transmission ; Male ; Microtubules/parasitology ; Microtubules/ultrastructure ; Plasmodium falciparum/cytology ; Plasmodium falciparum/genetics ; Plasmodium falciparum/growth & development ; Plasmodium falciparum/metabolism ; Reproduction, Asexual
    Language English
    Publishing date 2021-05-29
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 756166-0
    ISSN 1872-9428 ; 0166-6851
    ISSN (online) 1872-9428
    ISSN 0166-6851
    DOI 10.1016/j.molbiopara.2021.111385
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  2. Article ; Online: Targeting Aminoacyl tRNA Synthetases for Antimalarial Drug Development.

    Xie, Stanley C / Griffin, Michael D W / Winzeler, Elizabeth A / Ribas de Pouplana, Lluis / Tilley, Leann

    Annual review of microbiology

    2023  Volume 77, Page(s) 111–129

    Abstract: Infections caused by malaria parasites place an enormous burden on the world's poorest communities. Breakthrough drugs with novel mechanisms of action are urgently needed. As an organism that undergoes rapid growth and division, the malaria ... ...

    Abstract Infections caused by malaria parasites place an enormous burden on the world's poorest communities. Breakthrough drugs with novel mechanisms of action are urgently needed. As an organism that undergoes rapid growth and division, the malaria parasite
    MeSH term(s) Humans ; Antimalarials/pharmacology ; Antimalarials/therapeutic use ; Amino Acyl-tRNA Synthetases/chemistry ; Amino Acyl-tRNA Synthetases/genetics ; Amino Acyl-tRNA Synthetases/metabolism ; Plasmodium falciparum/genetics ; Malaria/drug therapy ; RNA, Transfer/genetics ; RNA, Transfer/metabolism ; RNA, Transfer/therapeutic use
    Chemical Substances Antimalarials ; Amino Acyl-tRNA Synthetases (EC 6.1.1.-) ; RNA, Transfer (9014-25-9)
    Language English
    Publishing date 2023-04-05
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 207931-8
    ISSN 1545-3251 ; 0066-4227
    ISSN (online) 1545-3251
    ISSN 0066-4227
    DOI 10.1146/annurev-micro-032421-121210
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  3. Article ; Online: Malaria parasites fine-tune mutations to resist drugs.

    Tilley, Leann / Rosenthal, Philip J

    Nature

    2019  Volume 576, Issue 7786, Page(s) 217–219

    MeSH term(s) Animals ; Antimalarials ; Drug Resistance/drug effects ; Malaria/parasitology ; Mutation/drug effects ; Parasites/drug effects ; Plasmodium falciparum/drug effects
    Chemical Substances Antimalarials
    Language English
    Publishing date 2019-12-10
    Publishing country England
    Document type News ; Comment
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-019-03587-0
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  4. Article ; Online: K13, the Cytostome, and Artemisinin Resistance.

    Xie, Stanley C / Ralph, Stuart A / Tilley, Leann

    Trends in parasitology

    2020  Volume 36, Issue 6, Page(s) 533–544

    Abstract: Artemisinins - the frontline antimalarial drug class - are compromised by emerging resistance, putting at risk the lives of hundreds of thousands of people each year. Resistance is associated with mutations in a malaria parasite protein, called Kelch 13 ( ...

    Abstract Artemisinins - the frontline antimalarial drug class - are compromised by emerging resistance, putting at risk the lives of hundreds of thousands of people each year. Resistance is associated with mutations in a malaria parasite protein, called Kelch 13 (K13). Recent work suggests that K13 is located at the cytostome (cell mouth) that the parasite uses to take up hemoglobin. Here we explore the proposal that K13 mutations confer artemisinin resistance by dampening hemoglobin endocytosis. This model suggests that the resultant decrease in hemoglobin-derived heme reduces artemisinin activation, which is sufficient to enable parasite survival in the early ring stage of infection. A fuller understanding of the resistance mechanism will underpin efforts to develop alternative antimalarial strategies.
    MeSH term(s) Antimalarials/pharmacology ; Artemisinins/pharmacology ; Drug Resistance/genetics ; Heme/metabolism ; Humans ; Mutation ; Plasmodium/drug effects ; Plasmodium/genetics ; Plasmodium/metabolism ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism
    Chemical Substances Antimalarials ; Artemisinins ; Protozoan Proteins ; Heme (42VZT0U6YR)
    Language English
    Publishing date 2020-04-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2036227-4
    ISSN 1471-5007 ; 1471-4922
    ISSN (online) 1471-5007
    ISSN 1471-4922
    DOI 10.1016/j.pt.2020.03.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Plasmodium falciparum goes bananas for sex

    Dixon, Matthew W.A / Tilley, Leann

    Molecular and biochemical parasitology. 2021 July, v. 244

    2021  

    Abstract: The sexual blood stages of the human malaria parasite Plasmodium falciparum undergo a remarkable transformation from a roughly spherical shape to an elongated crescent or “falciform” morphology from which the species gets its name. In this review, the ... ...

    Abstract The sexual blood stages of the human malaria parasite Plasmodium falciparum undergo a remarkable transformation from a roughly spherical shape to an elongated crescent or “falciform” morphology from which the species gets its name. In this review, the molecular events that drive this spectacular shape change are discussed and some questions that remain regarding the mechanistic underpinnings are posed. We speculate on the role of the shape changes in promoting sequestration and release of the developing gametocyte, thereby facilitating parasite survival in the host and underpinning transmission to the mosquito vector.
    Keywords Plasmodium falciparum ; blood ; humans ; malaria ; mosquito vectors ; parasites ; parasitology
    Language English
    Dates of publication 2021-07
    Publishing place Elsevier B.V.
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 756166-0
    ISSN 1872-9428 ; 0166-6851
    ISSN (online) 1872-9428
    ISSN 0166-6851
    DOI 10.1016/j.molbiopara.2021.111385
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Deletion of the Plasmodium falciparum exported protein PTP7 leads to Maurer's clefts vesiculation, host cell remodeling defects, and loss of surface presentation of EMP1.

    Carmo, Olivia M S / Shami, Gerald J / Cox, Dezerae / Liu, Boyin / Blanch, Adam J / Tiash, Snigdha / Tilley, Leann / Dixon, Matthew W A

    PLoS pathogens

    2022  Volume 18, Issue 8, Page(s) e1009882

    Abstract: Presentation of the variant antigen, Plasmodium falciparum erythrocyte membrane protein 1 (EMP1), at knob-like protrusions on the surface of infected red blood cells, underpins the parasite's pathogenicity. Here we describe a protein PF3D7_0301700 (PTP7), ...

    Abstract Presentation of the variant antigen, Plasmodium falciparum erythrocyte membrane protein 1 (EMP1), at knob-like protrusions on the surface of infected red blood cells, underpins the parasite's pathogenicity. Here we describe a protein PF3D7_0301700 (PTP7), that functions at the nexus between the intermediate trafficking organelle, the Maurer's cleft, and the infected red blood cell surface. Genetic disruption of PTP7 leads to accumulation of vesicles at the Maurer's clefts, grossly aberrant knob morphology, and failure to deliver EMP1 to the red blood cell surface. We show that an expanded low complexity sequence in the C-terminal region of PTP7, identified only in the Laverania clade of Plasmodium, is critical for efficient virulence protein trafficking.
    MeSH term(s) Erythrocyte Membrane/metabolism ; Erythrocytes/metabolism ; Organelles/metabolism ; Plasmodium falciparum/metabolism ; Protein Transport ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism
    Chemical Substances Protozoan Proteins
    Language English
    Publishing date 2022-08-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1009882
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  7. Article ; Online: Repurposing the mitotic machinery to drive cellular elongation and chromatin reorganisation in Plasmodium falciparum gametocytes.

    Li, Jiahong / Shami, Gerald J / Cho, Ellie / Liu, Boyin / Hanssen, Eric / Dixon, Matthew W A / Tilley, Leann

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 5054

    Abstract: The sexual stage gametocytes of the malaria parasite, Plasmodium falciparum, adopt a falciform (crescent) shape driven by the assembly of a network of microtubules anchored to a cisternal inner membrane complex (IMC). Using 3D electron microscopy, we ... ...

    Abstract The sexual stage gametocytes of the malaria parasite, Plasmodium falciparum, adopt a falciform (crescent) shape driven by the assembly of a network of microtubules anchored to a cisternal inner membrane complex (IMC). Using 3D electron microscopy, we show that a non-mitotic microtubule organizing center (MTOC), embedded in the parasite's nuclear membrane, orients the endoplasmic reticulum and the nascent IMC and seeds cytoplasmic microtubules. A bundle of microtubules extends into the nuclear lumen, elongating the nuclear envelope and capturing the chromatin. Classical mitotic machinery components, including centriolar plaque proteins, Pfcentrin-1 and -4, microtubule-associated protein, End-binding protein-1, kinetochore protein, PfNDC80 and centromere-associated protein, PfCENH3, are involved in the nuclear microtubule assembly/disassembly process. Depolymerisation of the microtubules using trifluralin prevents elongation and disrupts the chromatin, centromere and kinetochore organisation. We show that the unusual non-mitotic hemispindle plays a central role in chromatin organisation, IMC positioning and subpellicular microtubule formation in gametocytes.
    MeSH term(s) Centromere ; Chromatin ; Kinetochores ; Microtubules ; Plasmodium falciparum
    Chemical Substances Chromatin
    Language English
    Publishing date 2022-08-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-32579-4
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  8. Article ; Online: Repurposing the mitotic machinery to drive cellular elongation and chromatin reorganisation in Plasmodium falciparum gametocytes

    Jiahong Li / Gerald J. Shami / Ellie Cho / Boyin Liu / Eric Hanssen / Matthew W. A. Dixon / Leann Tilley

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 15

    Abstract: The sexual blood stages of Plasmodium falciparum develop through five morphologically distinct stages culminating in mature crescent-shaped gametocytes that can be transmitted from the mammalian host to the mosquito vector. Here, Li et al. apply ... ...

    Abstract The sexual blood stages of Plasmodium falciparum develop through five morphologically distinct stages culminating in mature crescent-shaped gametocytes that can be transmitted from the mammalian host to the mosquito vector. Here, Li et al. apply different microscopy and tomography approaches to characterize how the microtubule organizing center and cytoplasmic and nuclear microtubules are organized and oriented during these different stages in the absence of genome replication and mitosis.
    Keywords Science ; Q
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Plasmodium falciparum formins are essential for invasion and sexual stage development.

    Collier, Sophie / Pietsch, Emma / Dans, Madeline / Ling, Dawson / Tavella, Tatyana A / Lopaticki, Sash / Marapana, Danushka S / Shibu, Mohini A / Andrew, Dean / Tiash, Snigdha / McMillan, Paul J / Gilson, Paul / Tilley, Leann / Dixon, Matthew W A

    Communications biology

    2023  Volume 6, Issue 1, Page(s) 861

    Abstract: The malaria parasite uses actin-based mechanisms throughout its lifecycle to control a range of biological processes including intracellular trafficking, gene regulation, parasite motility and invasion. In this work we assign functions to the Plasmodium ... ...

    Abstract The malaria parasite uses actin-based mechanisms throughout its lifecycle to control a range of biological processes including intracellular trafficking, gene regulation, parasite motility and invasion. In this work we assign functions to the Plasmodium falciparum formins 1 and 2 (FRM1 and FRM2) proteins in asexual and sexual blood stage development. We show that FRM1 is essential for merozoite invasion and FRM2 is required for efficient cell division. We also observed divergent functions for FRM1 and FRM2 in gametocyte development. Conditional deletion of FRM1 leads to a delay in gametocyte stage progression. We show that FRM2 controls the actin and microtubule cytoskeletons in developing gametocytes, with premature removal of the protein resulting in a loss of transmissible stage V gametocytes. Lastly, we show that targeting formin proteins with the small molecule inhibitor of formin homology domain 2 (SMIFH2) leads to a multistage block in asexual and sexual stage parasite development.
    MeSH term(s) Actins/genetics ; Formins ; Plasmodium falciparum/genetics ; Cell Division ; Cytoskeleton
    Chemical Substances Actins ; Formins
    Language English
    Publishing date 2023-08-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-023-05233-y
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  10. Article ; Online: The proteasome as a target for protozoan parasites.

    Xie, Stanley C / Dick, Lawrence R / Gould, Alexandra / Brand, Stephen / Tilley, Leann

    Expert opinion on therapeutic targets

    2019  Volume 23, Issue 11, Page(s) 903–914

    Abstract: ... ...

    Abstract Introduction
    MeSH term(s) Animals ; Antiprotozoal Agents/pharmacology ; Drug Development ; Humans ; Parasites/isolation & purification ; Proteasome Endopeptidase Complex/drug effects ; Proteasome Endopeptidase Complex/metabolism ; Proteasome Inhibitors/pharmacology ; Protozoan Infections/drug therapy ; Protozoan Infections/parasitology
    Chemical Substances Antiprotozoal Agents ; Proteasome Inhibitors ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2019-11-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2055208-7
    ISSN 1744-7631 ; 1472-8222
    ISSN (online) 1744-7631
    ISSN 1472-8222
    DOI 10.1080/14728222.2019.1685981
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