A5013096500- Nuclear physics research studies
- Malaria Research and Control
- Nuclear Physics and Applications
- Quantum Chromodynamics and Particle Interactions
- Mosquito-borne diseases and control
- Advanced Chemical Physics Studies
- Advanced NMR Techniques and Applications
- RNA and protein synthesis mechanisms
- Particle physics theoretical and experimental studies
- RNA Research and Splicing
- Atomic and Subatomic Physics Research
- Parasitic Infections and Diagnostics
- Atomic and Molecular Physics
- Medical Imaging Techniques and Applications
- Invertebrate Immune Response Mechanisms
- Toxoplasma gondii Research Studies
- Neutrino Physics Research
- Microbial infections and disease research
- X-ray Spectroscopy and Fluorescence Analysis
- Trypanosoma species research and implications
- HIV/AIDS drug development and treatment
- High-Energy Particle Collisions Research
- Quantum, superfluid, helium dynamics
- Plant biochemistry and biosynthesis
- Advanced MRI Techniques and Applications
The University of Melbourne
2016-2025
London Health Sciences Centre
2023-2025
Western University
2025
Harvard University
2020
National Health and Medical Research Council
2020
Weatherford College
2012
Stanford University
1998-2004
Indiana University Bloomington
1990-2001
Ohio University
1985-1999
University of Victoria
1998
Glutathione S-transferases (GSTs) traditionally have been studied in plants and other organisms for their ability to detoxify chemically diverse herbicides toxic organic compounds. Anthocyanins are among the few endogenous substrates of plant GSTs that identified. The Bronze2 (Bz2) gene encodes a type III GST performs last genetically defined step maize anthocyanin pigment pathway. This is conjugation glutathione cyanidin 3-glucoside (C3G). Glutathionated C3G transported vacuole via...
Anthocyanin biosynthesis is one of the most thoroughly studied enzymatic pathways in biology, but little known about molecular mechanisms its final stage: transport anthocyanin pigment into vacuole. We have identified a multidrug resistance–associated protein (MRP), ZmMrp3, that required for this process maize (Zea mays). ZmMrp3 expression controlled by regulators and mirrors other structural genes. Localization ZmMRP3 vivo shows presence tonoplast, site at which occurs. Mutants generated...
Abstract AN9 is a glutathione S-transferase from petunia (Petunia hybrida) required for efficient anthocyanin export the site of synthesis in cytoplasm into permanent storage vacuole. For many xenobiotics it well established that covalent (GSH) tag mediates recognition molecules destined vacuolar sequestration by tonoplast-localized ATP-binding cassette pump. Here we inquired whether catalyzes formation GSH conjugates with flavonoid substrates. Using high-performance liquid chromatography...
Apicomplexa are important pathogens that include the causative agents of malaria, toxoplasmosis, and cryptosporidiosis. Apicomplexan parasites contain a relict chloroplast, apicoplast. The apicoplast is indispensable an attractive drug target. home to 1-deoxy-d-xylulose-5-phosphate (DOXP) pathway for synthesis isoprenoid precursors. This believed be most conserved function apicoplast, fosmidomycin, specific inhibitor pathway, effective antimalarial. Surprisingly, fosmidomycin has no effect...
Drug resistance compromises control of malaria. Here, we show that to a commonly used antimalarial medication, atovaquone, is apparently unable spread. Atovaquone pressure selects parasites with mutations in cytochrome b, respiratory protein low but essential activity the mammalian blood phase parasite life cycle. Resistance rescue from drug later prove lethal mosquito phase, where require full respiration. Unable respire efficiently, resistant fail complete development, arresting their...
Most current antimalarials for treatment of clinical Plasmodium falciparum malaria fall into two broad drug families and target the food vacuole trophozoite stage. No have been shown to brief extracellular merozoite form blood-stage malaria. We studied a panel 12 drugs, 10 which used extensively clinically, their invasion, schizont rupture, growth-inhibitory activity using high-throughput flow cytometry new approaches study invasion early intraerythrocytic development. Not surprisingly,...
Mitochondrial ATP synthase is driven by chemiosmotic oxidation of pyruvate derived from glycolysis. Blood-stage malaria parasites eschew chemiosmosis, instead relying almost solely on glycolysis for their generation, which begs the question whether mitochondrial necessary during blood stage parasite life cycle. We knocked out β subunit gene in rodent parasite, Plasmodium berghei, ablating protein that converts ADP to ATP. Disruption only marginally reduced asexual blood-stage growth but...
The clinical symptoms of malaria are caused by the asexual replication Plasmodium parasites in blood vertebrate host. To spread to new hosts, however, parasite must differentiate into sexual forms, termed gametocytes, which ingested a mosquito vector. Sexual differentiation produces either female or male and involves significant morphological biochemical changes. These transformations prepare gametocytes for rapid progression gamete formation fertilisation, occur within 20 min ingestion....
Histone deacetylase (HDAC) enzymes posttranslationally modify lysines on histone and nonhistone proteins play crucial roles in epigenetic regulation other important cellular processes. HDAC inhibitors (e.g., suberoylanilide hydroxamic acid [SAHA; also known as vorinostat]) are used clinically to treat some cancers under investigation for use against many diseases. Development of new noncancer indications has the potential be accelerated by piggybacking onto cancer studies, several have...
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...
Malaria invasion of red blood cells involves multiple parasite-specific targets that are easily accessible to inhibitory compounds, making it an attractive target for antimalarial development. However, no current agents act against host cell invasion. Here, we demonstrate the clinically used macrolide antibiotic azithromycin, which is known kill human malaria asexual blood-stage parasites by blocking protein synthesis in their apicoplast, also a rapid inhibitor (Plasmodium falciparum) and...
With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant M-833 and identify mutations in START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 into wildtype reproduces as well more potent analogues. binding analogues validated using organic solvent-based...
ABSTRACT Live cell imaging of human malaria parasites Plasmodium falciparum during gametocytogenesis revealed that the apicoplast does not grow, whereas mitochondrion undergoes remarkable morphological development. A close connection two organelles is consistently maintained. The and are components male gametes, suggesting maternal inheritance.
Therapies to prevent transmission of malaria parasites the mosquito vector are a vital part global elimination agenda. Primaquine is currently only drug with such activity; however, its use limited by side effects. The development transmission-blocking strategies requires an understanding sexual stage parasite (gametocyte) biology and identification new leads. Lysine acetylation important posttranslational modification involved in regulating eukaryotic gene expression other essential...
Malaria parasites contain a relict plastid, the apicoplast, which is considered an excellent drug target due to its bacterial-like ancestry. Numerous parasiticidals have been proposed but few had their actual targets substantiated. Isopentenyl pyrophosphate (IPP) production sole required function of apicoplast in blood stage parasite life cycle, and IPP supplementation rescues from apicoplast-perturbing drugs. Hence, any that kills when supplied culture must nonapicoplast target. Here, we...
Abstract Plasmodium falciparum causes most malaria deaths. Its developmental transitions and environmental adaptation are partially regulated by epigenetic mechanisms. GCN5 (PfGCN5) is an regulator that acetylates lysines can also bind to acetylated lysine residues on histones via its bromodomain (BRD). Here, we showed PfGCN5 was essential for parasite transmission survival in human blood mosquitoes. genes important metabolism development BRD required at euchromatic gene promoters their...