A5055274313- Malaria Research and Control
- Mosquito-borne diseases and control
- Cellular Mechanics and Interactions
- Complement system in diseases
- Enzyme Structure and Function
- Proteins in Food Systems
- Drug Transport and Resistance Mechanisms
- Reproductive System and Pregnancy
- Protein Hydrolysis and Bioactive Peptides
- Vector-borne infectious diseases
- Erythrocyte Function and Pathophysiology
- Microtubule and mitosis dynamics
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Invertebrate Immune Response Mechanisms
- Hemoglobinopathies and Related Disorders
- Endoplasmic Reticulum Stress and Disease
- Caveolin-1 and cellular processes
- Milk Quality and Mastitis in Dairy Cows
- Bacterial Genetics and Biotechnology
- Ubiquitin and proteasome pathways
- Lipid Membrane Structure and Behavior
- Endometriosis Research and Treatment
- Innovative Microfluidic and Catalytic Techniques Innovation
- Food composition and properties
- Enzyme Catalysis and Immobilization
Walter and Eliza Hall Institute of Medical Research
2011-2024
The University of Melbourne
2011-2024
CSIRO Manufacturing
2017-2024
Commonwealth Scientific and Industrial Research Organisation
2018-2024
Plant Industry
2024
Health Sciences and Nutrition
2023
Centro Nacional de Biotecnología
2020
Institute of Cell Biology
2006
University of Massachusetts Chan Medical School
2000-2005
La Trobe University
1997-2002
Plasma membranes are organized into functional domains both by liquid-ordered packing "lipid rafts," structures that resist Triton extraction, and attachments to underlying cytoskeletal proteins in assemblies called "membrane skeletons." Although the actin cytoskeleton is implicated many lipid raft-mediated signaling processes, little known about biochemical basis for involvement. We show here a subset of plasma membrane skeleton from bovine neutrophils co-isolates with cholesterol-rich,...
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...
Plasmodium falciparum exports several hundred effector proteins that remodel the host erythrocyte and enable parasites to acquire nutrients, sequester in circulation evade immune responses. The majority of exported contain export element (PEXEL; RxLxE/Q/D) their N-terminus, which is proteolytically cleaved parasite endoplasmic reticulum by Plasmepsin V, necessary for export. Several lack a PEXEL or noncanonical motifs. Here, we assessed whether V could process N-termini diverse protein...
Apicomplexan parasites are obligate intracellular that infect a variety of hosts, causing significant diseases in livestock and humans. The invasive forms the invade their host cells by gliding motility, an active process driven parasite adhesion proteins molecular motors. A crucial point during cell invasion is formation ring-shaped area intimate contact between known as tight junction. As zoite propels itself into host-cell, junction moves down length parasite. This must be tightly...
Abstract Neutrophil extracellular traps (NETs) and the cell death associated with it (NETosis) have been implicated in numerous diseases. Mechanistic studies of NETosis typically relied on nonphysiological stimuli, such as PMA. The human disease gout is caused by monosodium urate (MSU) crystals. We observed that DNA consistent NETs present fluid from acutely inflamed joints patients. also coat crystals found uninflamed tophi chronic developed a quantitative, live imaging assay, which...
Mature red blood cells (RBCs) lack internal organelles and canonical defense mechanisms, making them both a fascinating host cell, in general, an intriguing choice for the deadly malaria parasite Plasmodium falciparum (Pf), particular. Pf, while growing inside its natural host, human RBC, secretes multipurpose extracellular vesicles (EVs), yet their influence on this essential cell remains unknown. Here we demonstrate that Pf parasites, cultured fresh donor blood, secrete within such EVs...
Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential micronemal release gliding motility, yet target activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma cell invasion. Stimulation live tachyzoites with Ca2+-mobilizing drugs leads numerous parasite proteins, as shown by differential 2-DE display 32[P]-labeled protein...
Plasmodium parasites remodel their vertebrate host cells by translocating hundreds of proteins across an encasing membrane into the cell cytosol via a putative export machinery termed PTEX. Previously PTEX150, HSP101 and EXP2 have been shown to be bona fide members Here we validate that PTEX88 TRX2 are also genuine PTEX provide evidence expression components expressed in early gametocytes, mosquito liver stages, consistent with observations protein is not restricted asexual stages. Although...
The Plasmodium translocon for exported proteins (PTEX) has been established as the machinery responsible translocation of all classes beyond parasitophorous vacuolar membrane intraerythrocytic malaria parasite. Protein export, particularly in asexual blood stage, is crucial parasite survival are involved remodelling host cell, an essential process nutrient uptake, waste removal and immune evasion. Here, we have truncated conserved C-terminus one PTEX components, PTEX150, falciparum attempt...
Abstract Plasmodium falciparum exports proteins into erythrocytes using the export element (PEXEL) motif, which is cleaved in endoplasmic reticulum (ER) by plasmepsin V (PMV). A recent study reported that phosphatidylinositol-3-phosphate (PI(3)P) concentrated ER binds to PEXEL motifs and required for independent of PMV, are functionally interchangeable with RxLR oomycete effectors. Here we show does not bind PI(3)P, this lipid ER. We find cannot mediate P. . Parasites expressing a mutated...
The most lethal form of malaria in humans is caused by Plasmodium falciparum. These parasites invade erythrocytes, a complex process involving multiple ligand-receptor interactions. parasite makes initial contact with the erythrocyte followed dramatic deformations linked to function Erythrocyte binding antigen family and P. falciparum reticulocyte binding-like families. We show EBA-175 mediates substantial changes deformability erythrocytes glycophorin A activating phosphorylation cascade...
Abstract Megakaryocytes (MK) generate platelets. Recently, we and others, have reported MK also regulate hematopoietic stem cells (HSC). Here show high ploidy large cytoplasmic megakaryocytes (LCM) are critical negative regulators of HSC for platelet formation. Using a mouse knockout model ( Pf4-Srsf3 Δ/Δ ) with normal numbers, but essentially devoid LCM, demonstrate pronounced increase in BM concurrent endogenous mobilization extramedullary hematopoiesis. Severe thrombocytopenia is observed...
Malaria is caused by five different Plasmodium spp. in humans each of which modifies the host erythrocyte to survive and replicate. The two main causes malaria, P. falciparum vivax, differ their ability cause severe disease, mainly due differences cytoadhesion infected erythrocytes (IE) microvasculature. Cytoadhesion brain leads a large number deaths year consequence exported parasite proteins, some modify cytoskeleton while others such as PfEMP1 project onto surface where they bind...
How is endometrial epithelial receptivity, particularly adhesiveness, regulated at the luminal surface for embryo implantation in human?Podocalyxin (PCX), a transmembrane protein, was identified as key negative regulator of receptivity; specific downregulation PCX epithelium mid-secretory phase, likely mediated by progesterone, may act critical step converting from non-receptive to an implantation-permitting state.The human endometrium must undergo major molecular and cellular changes...
ABSTRACT We measured folate- and cAMP-induced changes in cytoplasmic free calcium concentration ([Ca2+]i) using recombinant aequorin reconstituted living Dictyostelium cells with coelenterazine-h. The resulting semi-synthetic protein displayed increased sensitivity to Ca2+ allowing accurate measurement of chemoattractant-induced transients at low resting levels. Both responses were developmentally regulated, exhibited remarkably similar kinetics dependent on the relative rather than absolute...