A5013131908- Malaria Research and Control
- Mosquito-borne diseases and control
- Invertebrate Immune Response Mechanisms
- Complement system in diseases
- Drug Transport and Resistance Mechanisms
- Trypanosoma species research and implications
- Herpesvirus Infections and Treatments
- Animal Disease Management and Epidemiology
- Research on Leishmaniasis Studies
- Vector-borne infectious diseases
- HIV Research and Treatment
- Aquaculture disease management and microbiota
- Toxoplasma gondii Research Studies
- Computational Drug Discovery Methods
- Immunotherapy and Immune Responses
- Viral Infections and Immunology Research
- Immune Cell Function and Interaction
- Parasites and Host Interactions
- Cytomegalovirus and herpesvirus research
- Animal Virus Infections Studies
- vaccines and immunoinformatics approaches
- Viral-associated cancers and disorders
- HIV/AIDS drug development and treatment
- COVID-19 epidemiological studies
- Influenza Virus Research Studies
The University of Melbourne
2015-2024
Burnet Institute
2015-2024
Monash University
2014-2024
Deakin University
2023
Papua New Guinea University of Natural Resources and Environment
2020-2021
Peter Doherty Institute
2014-2021
Parks Victoria
2019
Australian Regenerative Medicine Institute
2017-2018
Discovery Institute
2016
The Royal Melbourne Hospital
2001-2015
The human malaria parasite Plasmodium vivax is responsible for 25–40% of the ∼515 million annual cases worldwide. Although seldom fatal, elicits severe and incapacitating clinical symptoms often causes relapses months after a primary infection has cleared. Despite its importance as major pathogen, P. little studied because it cannot be propagated continuously in laboratory except non-human primates. We sequenced genome to shed light on distinctive biological features, means drive development...
A major part of virulence for Plasmodium falciparum malaria infection, the most lethal parasitic disease humans, results from increased rigidity and adhesiveness infected host red cells. These changes are caused by parasite proteins exported to erythrocyte using novel trafficking machinery assembled in cell. To understand these unique modifications, we used a large-scale gene knockout strategy combined with functional screens identify into parasite-infected erythrocytes involved remodeling...
During blood stage Plasmodium falciparum infection, merozoites invade uninfected erythrocytes via a complex, multistep process involving series of distinct receptor-ligand binding events. Understanding each element in this increases the potential to block parasite's life cycle drugs or vaccines. To investigate specific interactions, they were systematically blocked using combination genetic deletion, enzymatic receptor cleavage and inhibition antibodies, peptides small molecules, resulting...
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....
Genetic studies of the protozoan parasite Plasmodium falciparum have been severely limited by inability to introduce or modify genes. In this paper we describe a system stable transfection P. using Toxoplasma gondii dihydrofolate reductase-thymidylate synthase gene, modified confer resistance pyrimethamine, as selectable marker. This gene was placed under transcriptional control calmodulin flanking sequences. Transfected parasites generally maintained plasmids episomally while selection;...
Antibodies that bind to antigens expressed on the merozoite form of malaria parasite can inhibit growth by preventing invasion red blood cells. Inhibitory antibodies are found in sera malaria-immune individuals, however, specificity those important this process is not known. In paper, we have used allelic replacement construct a Plasmodium falciparum line expresses complete COOH-terminal fragment surface protein (MSP)-119 from divergent rodent P. chabaudi. By comparing transfected with...
Most proteins that coat the surface of extracellular forms human malaria parasite Plasmodium falciparum are attached to plasma membrane via glycosylphosphatidylinositol (GPI) anchors. These exposed neutralizing antibodies, and several advanced vaccine candidates. To identify GPI-anchored proteome P. we used a combination proteomic computational approaches. Focusing on clinically relevant blood stage life cycle, analysis labeled with radioactive glucosamine identified GPI anchoring 11...
Glycosylphosphatidylinositol (GPI)-anchored proteins coat the surface of extracellular Plasmodium falciparum merozoites, which several are highly validated candidates for inclusion in a blood-stage malaria vaccine. Here we determined proteome gradient-purified detergent-resistant membranes mature parasites and found that these greatly enriched GPI-anchored their putative interacting partners. Also prominent apical organelle (rhoptry), multimembrane-spanning, destined export into host...
Techniques for targeted genetic disruption in Plasmodium, the causative agent of malaria, are currently intractable those genes that essential blood stage development. The ability to use RNA interference (RNAi) silence gene expression would provide a powerful means gain valuable insight into pathogenic stages but its functionality Plasmodium remains controversial. Here we have used various RNA-based silencing approaches test utility RNAi malaria parasites and undertaken an extensive...
Erythrocyte invasion by Plasmodium requires molecules present both on the merozoite surface and within specialized organelles of apical complex. The erythrocyte binding protein family includes falciparum sialic acid-binding protein, EBA-175 (erythrocyte antigen-175), which binds acid glycophorin A human erythrocytes. We address role conserved 3′-cysteine rich region, transmembrane, cytoplasmic domains through targeted gene disruption. Truncation had no measurable effect either level...
Although CD8 + T cells do not contribute to protection against the blood stage of Plasmodium infection, there is mounting evidence that they are principal mediators murine experimental cerebral malaria (ECM). At present, no direct mediating ECM parasite-specific or, for matter, whether generated in response blood-stage infection. To resolve this and define cellular requirements such priming, we transgenic P. berghei parasites expressing model cell epitopes. This approach was necessary as MHC...
Methods to transiently and stably transfect blood stages of the human malaria parasite Plasmodium falciparum have been developed adapted for gene-knockout, allelic replacement, transgene expression in this organism. These methods are detailed chapter, as approaches used monitor transfectants during selection process. The different plasmid vectors that currently gene targeting (including green fluorescent protein expression) also described.
Cerebral malaria is a severe complication of malaria. Sequestration parasitized RBCs in brain microvasculature associated with disease pathogenesis, but our understanding this process incomplete. In study, we examined parasite tissue sequestration an experimental model cerebral (ECM). We show that rapid increase biomass strongly the induction ECM, mediated by IFN-gamma and lymphotoxin alpha, whereas TNF IL-10 limit process. Crucially, discovered host CD4(+) CD8(+) T cells promote...
Malaria parasites modify their host cell, the mature human erythrocyte. We are interested in molecules mediating these processes, and have recently described a family of parasite-encoded heat shock proteins (PfHsp40s) that targeted to implicated cell modification. Hsp40s generally function as co-chaperones members Hsp70 family, until now it was thought acts PfHsp40 interaction partner within cell. Here we revise this hypothesis, identify characterize an exported Hsp70, referred PfHsp70-x....