A5008548030- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Carbohydrate Chemistry and Synthesis
- Parasitic Infections and Diagnostics
- Glycosylation and Glycoproteins Research
- Biochemical and Molecular Research
- Lysosomal Storage Disorders Research
- Mosquito-borne diseases and control
- Toxoplasma gondii Research Studies
- Malaria Research and Control
- Agricultural pest management studies
- Parasites and Host Interactions
- Insect and Pesticide Research
- Mycobacterium research and diagnosis
- Transgenic Plants and Applications
- Enzyme Production and Characterization
- Toxin Mechanisms and Immunotoxins
- HIV/AIDS drug development and treatment
- Legume Nitrogen Fixing Symbiosis
- Tuberculosis Research and Epidemiology
- Pancreatitis Pathology and Treatment
- RNA regulation and disease
- HIV Research and Treatment
- Click Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
The University of Melbourne
2007-2024
University of Dundee
1993-1994
Monash University
1989
Apicomplexa are parasitic protozoa that cause important human diseases including malaria, cryptosporidiosis and toxoplasmosis. The replication of these parasites within their target host cell is dependent on both salvage as well de novo synthesis fatty acids. In Toxoplasma gondii, acid via the apicoplast-localized FASII essential for pathogenesis, while role two other biosynthetic complexes remains unclear. Here, we demonstrate ER-localized elongation (ELO) parasite growth. Conditional...
Glycosylphosphatidylinositol (GPI) glycolipids are major cell surface constituents in the Leishmania parasites. Distinct classes of GPI present as membrane anchors for several glycoproteins and an abundant lipophosphoglycan well being (GIPLs) plasma membrane. In this study we have identified putative precursors protein delineated complete pathway GIPL biosynthesis mexicana promastigotes. Based on structural analyses these intermediates their kinetics labeling vivo cell-free systems, provide...
Pathogenic species of Mycobacteria and Corynebacteria, including Mycobacterium tuberculosis Corynebacterium diphtheriae, synthesize complex cell walls that are rich in very long-chain mycolic acids. These fatty acids synthesized on the inner leaflet membrane subsequently transported to periplasmic space as trehalose monomycolates (TMM), where they conjugated other wall components TMM form dimycolates (TDM). Mycobacterial TMM, equivalent glutamicum corynomycolates (TMCM), across by MmpL3, or...
The protozoan parasite Leishmania mexicana proliferates within macrophage phagolysosomes in the mammalian host. In this study we provide evidence that a novel class of intracellular β1-2 mannan oligosaccharides is important for survival host macrophages. Mannan (degree polymerization 4-40) expressed at low levels non-pathogenic promastigote stages but constitutes 80 and 90% cellular carbohydrate two developmental infect macrophages, non-dividing promastigotes, lesion-derived amastigotes,...
Parasitic protists belonging to the genus Leishmania synthesize non-canonical carbohydrate reserve, mannogen, which is composed of β-1,2-mannan oligosaccharides. Here, we identify a class dual-activity mannosyltransferase/phosphorylases (MTPs) that catalyze both sugar nucleotide-dependent biosynthesis and phosphorolytic turnover mannogen. Structural phylogenic analysis shows while MTPs are structurally related bacterial mannan phosphorylases, they constitute distinct family...
Glycophosphatidylinositol (GPI) anchors are the predominant glycoconjugate in Plasmodium parasites, enabling modified proteins to associate with biological membranes. GPI biosynthesis commences donation of a mannose residue held by dolichol-phosphate at endoplasmic reticulum membrane. In dolichols derived from isoprenoid precursors synthesised apicoplast, relict plastid organelle prokaryotic origin. We found that treatment parasites apicoplast inhibitors decreases synthesis and intermediates...
In this paper we have analyzed the effects of mannosamine on glycosylphosphatidylinositol anchor and variant surface glycoprotein biosynthesis in bloodstream form T. brucei.Trypanosomes were biosynthetically labeled with [SH]mannosamine, [3Hlglucosamine presence mannosamine, structures glycolipids which accumulated determined.The main glycolipid metabolite was shown to be ManN-Man-GlcN-PI.A trypanosome cell-free system preloaded compound significantly impaired its ability synthesize...
The non-alpha-helical N-terminal domain of intermediate filament proteins plays a key role in assembly. Previous studies have identified nonapeptide motif, SSYRRIFGG, the vimentin that is required for This motif also found desmin, peripherin and type IV proteins. GFAP only III protein which this not readily identified. study has two motifs mouse play important roles One located at very N terminus consensus sequence, MERRRITS-ARRSY. It some characteristics common with including its location...
The variant-specific surface proteins (VSPs) of the ancient protist Giardia duodenalis(syn.: intestinalis, lamblia) are cysteine- and threonine-rich polypeptides that can vary considerably in sequence size. In present study, we have purified a VSP (VSP4A1, formerly called CRISP-90) from cloned Giardiaisolate, derived sheep, by Triton X-114 phase partitioning anion-exchange chromatography. Analysis VSP4A1 showed this protein is post-translationally modified with both glycans lipid. were...
Glucuronosyl diacylglycerides (GlcAGroAc2) are functionally important glycolipids and membrane anchors for cell wall lipoglycans in the Corynebacteria. Here we describe complete synthesis of distinct acyl-isoforms GlcAGroAc2 bearing both acylation patterns (R)-tuberculostearic acid (C19:0) palmitic (C16:0) their mass spectral characterization. Collision-induced fragmentation spectrometry identified characteristic fragment ions that were used to develop "rules" allowing assignment pattern as...
Free glycosylphosphatidylinositols (GPIs) are an important class of membrane lipids in many pathogenic protozoa. In this study, we have investigated the subcellular distribution and intracellular trafficking abundant free GPIs [termed glycosylinositolphospholipids (GIPLs)] Leishmania mexicana promastigotes. The transport GIPLs major GPI-anchored glycoprotein gp63 was measured by following incorporation these molecules into sphingolipid-rich, detergent-resistant membranes (DRMs) plasma...
Infective stages of the protozoan parasite Leishmania spp. accumulate a class beta-1,2-mannan oligosaccharides as their major carbohydrate reserve material. Here, we describe biosynthesis mannan. Mannan precursors were identified by metabolic labeling mexicana promastigotes with [(3)H]mannose. Label was initially incorporated into phosphomannose primer and short phosphorylated oligomers that two to five residues long. Analysis mannan Fourier transform ion-cyclotron resonance MS various...
Leishmania spp. are human pathogens that utilize a novel beta-1,2-mannan as their major carbohydrate reserve material. We describe new approach combines traditional substrate-modification methods and "click chemistry" to assemble library of modified substrates were used qualitatively define the substrate tolerance beta-1,2-mannosyltransferases responsible for biosynthesis. The was assembled by using highly selective copper(I)-catalysed cycloaddition reaction azides alkynes couple an...
Leishmania are protozoan parasites that proliferate within the phagolysome of mammalian macrophages. While a number anti-oxidant systems in these have been shown to protect against endogenous as well host-generated reactive oxygen species, potential role enzymes involved repair oxidatively damaged proteins remains uncharacterized. The spp genomes encode single putative methionine sulfoxide reductase (MsrA) could reducing oxidized free and proteinogenic residues. A GFP-fusion L. major MsrA...
Parasitic protozoa, such as Leishmania species, are thought to express a number of surface and secreted nucleoside triphosphate diphosphohydrolases (NTPDases) which hydrolyze broad range tri- diphosphates. However, the functional significance NTPDases in parasite virulence is poorly defined. The major genome was found contain two putative NTPDases, termed LmNTPDase1 2, with predicted NTPDase catalytic domains either an N-terminal signal sequence and/or transmembrane domain, respectively....
Free glycosylphosphatidylinositols (GPIs) are an important class of membrane lipids in many pathogenic protozoa. In this study, we have investigated the subcellular distribution and intracellular trafficking abundant free GPIs [termed glycosylinositolphospholipids (GIPLs)] Leishmania mexicana promastigotes. The transport GIPLs major GPI-anchored glycoprotein gp63 was measured by following incorporation these molecules into sphingolipid-rich, detergent-resistant membranes (DRMs) plasma...
Leishmania spp. are a medically important group of protozoan parasites that synthesize novel intracellular carbohydrate reserve polymer termed mannogen. Mannogen is soluble homopolymer β-1,2-linked mannose residues accumulates in the major pathogenic stages sandfly vector and mammalian host. While several steps mannogen biosynthesis have been defined, none enzymes isolated or characterized. We report development simple assay for GDP-mannose–dependent β-1,2-mannosyltransferases involved...