A5040552653- Malaria Research and Control
- Mosquito-borne diseases and control
- Complement system in diseases
- Invertebrate Immune Response Mechanisms
- Trypanosoma species research and implications
- Drug Transport and Resistance Mechanisms
- Research on Leishmaniasis Studies
- Signaling Pathways in Disease
- Vector-borne infectious diseases
- Parasites and Host Interactions
- HIV Research and Treatment
- Computational Drug Discovery Methods
- Aquaculture disease management and microbiota
- vaccines and immunoinformatics approaches
- Biotechnology and Related Fields
- Toxin Mechanisms and Immunotoxins
- Hepatitis B Virus Studies
- Insect Resistance and Genetics
- Protein Structure and Dynamics
- Helminth infection and control
- Climate Change Communication and Perception
- Parasite Biology and Host Interactions
- Hemoglobinopathies and Related Disorders
- T-cell and B-cell Immunology
- Engineering and Material Science Research
The University of Melbourne
2006-2022
Walter and Eliza Hall Institute of Medical Research
2012-2022
Heidelberg Repatriation Hospital
2005
La Trobe University
2004
The Royal Melbourne Hospital
2000
University of Edinburgh
1997-1999
Imperial Valley College
1991
Apicomplexan parasites constitute one of the most significant groups pathogens infecting humans and animals. The liver stage sporozoites Plasmodium spp. tachyzoites Toxoplasma gondii, causative agents malaria toxoplasmosis, respectively, use a unique mode locomotion termed gliding motility to invade host cells cross cell substrates. This amoeboid-like movement uses parasite adhesin from thrombospondin-related anonymous protein (TRAP) family set proteins linking extracellular adhesin, via an...
Abstract The development of effective malaria vaccines and immune biomarkers is a high priority for control elimination. Ags expressed by merozoites Plasmodium falciparum are likely to be important targets human immunity promising vaccine candidates, but very few have been studied. We developed an approach assess Ab responses comprehensive repertoire merozoite proteins investigate whether they protective Abs. 91 recombinant proteins, located on the surface or within invasion organelles,...
Apical membrane antigen 1 (AMA1) is an asexual blood‐stage protein expressed in the invasive merozoite form of Plasmodia species, which are causative agent malaria. We have complemented function Plasmodium falciparum AMA1 (PfAMA1) with a divergent transgene from chabaudi ( PcAMA1 ). It was not possible to disrupt PfAMA1 gene using ‘knock‐out’ plasmids, although we demonstrate that can be targeted by homologous recombination. These experiments suggest critical, perhaps essential, for growth....
Summary Apical membrane antigen‐1 (AMA‐1) is a target of antibodies that inhibit invasion Plasmodium falciparum into human erythrocytes and candidate for inclusion in malaria vaccine. We have identified line P. (W2mef) less susceptible to anti‐AMA1 raised the protein from heterologous parasite (3D7). constructed transgenic expressing AMA‐1 alleles. In vitro assays show these parasites differ parental lines susceptibility inhibitory antibodies, providing direct evidence sequence polymorphisms...
ABSTRACT Plasmodium falciparum causes the most severe form of malaria in humans and invades erythrocytes using multiple ligand-receptor interactions. Two important protein families involved erythrocyte binding are binding-like (EBL) reticulocyte (RBL or P. Rh [PfRh]) proteins. We constructed lines lacking expression EBL proteins by creating single double knockouts corresponding genes for eba-175 , eba-181 eba-140 show that PfRh function cooperatively, consistent with them playing a similar...
Artemisin combination therapy (ACT) is the main treatment option for malaria, which caused by intracellular parasite Plasmodium. However, increased resistance to ACT highlights importance of finding new drugs. Recently, aspartic proteases Plasmepsin IX and X (PMIX PMX) were identified as promising drug targets. In this study, we describe dual inhibitors PMIX PMX, including WM382, that block multiple stages Plasmodium life cycle. We demonstrate PMX a master modulator merozoite invasion direct...
Abstract The most severe form of malaria is caused by Plasmodium falciparum . These parasites invade human erythrocytes, and an essential step in this process involves the ligand PfRh5, which forms a complex with cysteine-rich protective antigen (CyRPA) PfRh5-interacting protein (PfRipr) (RCR complex) binds basigin on host cell. We identified heteromeric disulfide-linked consisting P. thrombospondin-related apical merozoite (PfPTRAMP) small secreted (PfCSS) have shown that it RCR to...
Apical membrane antigen 1 of Plasmodium falciparum (PfAMA1) contains an N-terminal propeptide that is removed prior to the translocation mature protein onto merozoite surface. We localized unprocessed PfAMA1 microneme organelles intraerythrocytic schizont. The results have suggested processed form translocates from compartment independently another protein, EBA175, which also involved in invasion human erythrocytes.
Immunization with live-attenuated Plasmodium sporozoites completely protects against malaria infection. Genetic engineering offers a versatile platform to create sporozoite vaccine candidates. We previously generated genetically attenuated parasite (GAP) by deleting the P52 and P36 genes in NF54 wild-type (WT) strain of falciparum (Pf p52−/p36− GAP). Preclinical assessment GAP humanized mouse model indicated an early severe liver stage growth defect. However, human exposure >200 Pf...
The study of antigenic targets naturally-acquired immunity is essential to identify and prioritize antigens for further functional characterization. We measured total IgG antibodies 38 P. vivax antigens, investigating their relationship with prospective risk malaria in a cohort 1–3 years old Papua New Guinean children. Using simulated annealing algorithms, the potential protective efficacy multiple antigen-combinations, antibody thresholds associated protection were investigated first time....
Plasmodium falciparum causes the most severe form of malaria in humans and is responsible for over 700,000 deaths annually. It an obligate intracellular parasite invades erythrocytes where it grows a relatively protected niche. Invasion essential survival this involves interplay multiple protein–protein interactions. One important interactions binding invasion ligand families EBLs PfRhs to host receptors on surface erythrocytes. PfRh5 only within PfRh family vaccine candidate. binds receptor...
Abstract Host membrane remodeling is indispensable for viruses, bacteria, and parasites, to subvert the barrier obtain entry into cells. The malaria parasite Plasmodium spp . induces biophysical molecular changes erythrocyte through ordered secretion of its apical organelles. To understand this process address debate regarding how parasitophorous vacuole (PVM) formed, we developed an approach using lattice light-sheet microscopy, which enables interaction with host cell be tracked...
Antibodies to the sexual-stage surface antigens of Plasmodium falciparum, Pfs230 and Pfs48/45, can abolish infectivity gametes mosquitoes; these have been proposed as candidates for inclusion in a malaria transmission-blocking vaccine. One possible mechanism antibody-mediated transmission blocking is complement-mediated gamete lysis. We used panel human sera from geographically distinct regions where endemic investigate whether this may be naturally acquired immunity P. falciparum. By...
ABSTRACT Determining the diversity of PfEMP1 sequences expressed by Plasmodium falciparum -infected erythrocytes isolated from placentas is important for attempts to develop a pregnancy-specific malaria vaccine. The DBLγ and var2csa DBL3x domains molecules are believed mediate placental sequestration infected erythrocytes, so encoding these were amplified cDNAs parasites using degenerate oligonucleotides. levels specific var then determined quantitative reverse transcription-PCR. Homologues...
Summary Osmiophilic bodies are membrane‐bound vesicles, found predominantly in Plasmodium female gametocytes, that become progressively more abundant as the gametocyte reaches full maturity. These vesicles lie beneath subpellicular membrane of gametocyte, and release their contents into parasitophorous vacuole has been postulated to aid escape gametocytes from erythrocyte after ingestion by mosquito. Currently, only protein known be associated with osmiophilic falciparum is Pfg377, a...
One of the solutions for reducing global mortality and morbidity due to malaria is multivalent vaccines comprising antigens several life cycle stages malarial parasite. Hence, there a need supplementing current set vaccine candidate antigens. Here, we aimed characterize glycosylphosphatidylinositol (GPI)-anchored micronemal antigen (GAMA) encoded by PF08_0008 gene in Plasmodium falciparum. Antibodies were raised against recombinant GAMA synthesized using wheat germ cell-free system....
Plasmodium falciparum causes malaria in humans with over 450,000 deaths annually. The asexual blood stage involves invasion of erythrocytes by merozoites, which they grow and divide to release daughter turn invade new perpetuating the cycle responsible for malaria. A key step merozoite is essential binding PfRh5/CyRPA/PfRipr complex basigin, a linked formation pore between merozoites erythrocytes. We show CyRPA interacts directly PfRh5. An inhibitory monoclonal antibody blocks PfRh5 thus...