A5019459840- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Botulinum Toxin and Related Neurological Disorders
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Marine Toxins and Detection Methods
- Venomous Animal Envenomation and Studies
- Nicotinic Acetylcholine Receptors Study
- Neurological disorders and treatments
- Nerve injury and regeneration
- Erythrocyte Function and Pathophysiology
- Advanced Fluorescence Microscopy Techniques
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- Genetic Neurodegenerative Diseases
- Marine Invertebrate Physiology and Ecology
- Photoreceptor and optogenetics research
- Alzheimer's disease research and treatments
- SARS-CoV-2 and COVID-19 Research
- Biochemical and Structural Characterization
- Healthcare and Venom Research
- Retinal Development and Disorders
- Autophagy in Disease and Therapy
- Pain Mechanisms and Treatments
- Calcium signaling and nucleotide metabolism
Park Centre for Mental Health
2015-2024
The University of Queensland
2015-2024
Queensland Eye Institute
2009-2023
Australian e-Health Research Centre
2022-2023
Nanyang Technological University
2023
Joensuu Science Park
2023
Children's Medical Research Institute
2023
The University of Sydney
2023
Johns Hopkins University
2023
Allen Institute for Brain Science
2008-2022
The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome 2 (SARS-CoV-2). For many viruses, tissue tropism determined by availability virus receptors and entry cofactors on surface host cells. In this study, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked a monoclonal blocking antibody against NRP1. A mutant with altered furin cleavage site did not depend...
Blockade of acetylcholine release by botulinum neurotoxin type A at the neuromuscular junction induces formation an extensive network nerve-terminal sprouts. By repeated in vivo imaging N -(3-triethyl ammonium propyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide uptake into identified nerve endings mouse sternomastoid muscle after a single intramuscular injection toxin, inhibition stimulated dye terminals was detected within few days, together with increase staining newly formed After 28...
Dynamin GTPase activity increases when it oligomerizes either into helices in the presence of lipid templates or rings SH3 domain proteins. Dynasore is a dynamin inhibitor moderate potency ( IC 50 ˜ 15 μM vitro ). We show that dynasore binds stoichiometrically to detergents used for drug screening, drastically reducing its = 479 μM) and research tool utility. synthesized focused set dihydroxyl trihydroxyl analogs called Dyngo™ compounds, five which had improved potency, reduced detergent...
Numerous viruses use specialized surface molecules called fusogens to enter host cells. Many of these viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can infect brain and are associated with neurological symptoms through poorly understood mechanisms. We show that SARS-CoV-2 infection induces fusion between neurons glia in mouse human organoids. reveal this is caused by viral fusogen, as it fully mimicked expression spike (S) protein or unrelated fusogen...
Conotoxins (CTXs), with their exquisite specificity and potency, have recently created much excitement as drug leads. However, like most peptides, beneficial activities may potentially be undermined by susceptibility to proteolysis in vivo . By cyclizing the α-CTX MII using a range of linkers, we engineered peptides that preserve full activity but greatly improved resistance proteolytic degradation. The cyclic analogue containing seven-residue linker joining N C termini was active selective...
Journal Article Candidemia in Immunocompromised Patients Get access F. Meunier, Meunier * From the Service de Médecine Interne et Laboratoire d'Investigation Clinique Henri Tagnon, des Maladies Infectieuses Microbiologie, Institut Jules Bordet, Centre Tumeurs l'Université Libre Bruxelles Reprints or correspondence: Dr. EORTC Central Office—Data Center, 82 Av. E. Mounier, Boîte 11, 1200 Brussels, Belgium. This is Meunier's present affiliation. Search for other works by this author on: Oxford...
The botulinum neurotoxins (BoNTs) are di-chain bacterial proteins responsible for the paralytic disease botulism. Following binding to plasma membrane of cholinergic motor nerve terminals, BoNTs internalized into an endocytic compartment. Although several pathways have been characterized in neurons, molecular mechanism underpinning uptake at presynaptic terminal is still unclear. Here, a recombinant BoNT/A heavy chain domain (Hc) was used unravel internalization pathway by fluorescence and...
Botulinum neurotoxin type A (BoNT/A) is a highly potent that elicits flaccid paralysis by enzymatic cleavage of the exocytic machinery component SNAP25 in motor nerve terminals. However, recent evidence suggests neurotoxic activity BoNT/A not restricted to periphery, but also reaches CNS after retrograde axonal transport. Because internalized recycling synaptic vesicles, it unclear which compartment facilitates this Using live-cell confocal and single-molecule imaging rat hippocampal neurons...
SUMMARY The causative agent of the current pandemic and coronavirus disease 2019 (COVID-19) is severe acute respiratory syndrome 2 (SARS-CoV-2) 1 . Understanding how SARS-CoV-2 enters spreads within human organs crucial for developing strategies to prevent viral dissemination. For many viruses, tissue tropism determined by availability virus receptors on surface host cells Both SARS-CoV use angiotensin-converting enzyme (ACE2) as a receptor, yet, their tropisms differ 3-5 Here, we found that...
Neuronal activity causes use-dependent decline in protein function. However, it is unclear how this coupled to local quality control mechanisms. We show Drosophila that the endocytic Endophilin-A (EndoA) connects activity-induced calcium influx synaptic autophagy and neuronal survival a Parkinson disease-relevant fashion. Mutations disordered loop, including disease-risk mutation, render EndoA insensitive stimulation affect dynamics: when more flexible, its mobility membrane nanodomains...
The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation retained for later like BA.5 and XBB remains controversial. We show that isolates were significantly more pathogenic in K18-hACE2 mice than a isolate, showing increased neurotropic potential, resulting fulminant brain infection mortality, similar seen original ancestral isolates. also infected human cortical organoids greater extent In brains mice,...
Protein kinases (PKs) are proteins at the core of cellular signalling and thereby responsible for most physiological processes their regulations. As all intracellular proteins, PKs subjected to Brownian thermal energy that tends homogenise distribution throughout volume cell. To access substrates perform critical functions, PK localisation is therefore tightly regulated in space time, relying upon a range clustering mechanisms. These include post-translational modifications, protein-protein...
Abstract The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning memory, but the mechanisms through which activity affects brain’s lipid landscape remain largely unexplored. levels saturated FFAs, particularly myristic (C14:0), strongly increase during stimulation memory acquisition, suggesting involvement phospholipase A1 (PLA1) synaptic plasticity. Here, we show that genetic ablation PLA1 isoform DDHD2 mice dramatically reduces FFA...
Synaptotagmins are membrane proteins that possess tandem C2 domains and play an important role in regulated fusion metazoan organisms. Here we show both synaptotagmins I II, the two major neuronal isoforms, can interact with syntaxin/synaptosomal-associated protein of 25 kDa (SNAP-25) dimer, immediate precursor soluble NSF attachment receptor (SNARE) complex. A stretch basic amino acids highly conserved throughout animal kingdom is responsible for this calcium-independent interaction....
The lipid phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), synthesised by PIKfyve, regulates a number of intracellular membrane trafficking pathways. Genetic alteration the PIKfyve complex, leading to even mild reduction in PtdIns(3,5)P2, results marked neurodegeneration via an uncharacterised mechanism. In present study we have shown that selectively inhibiting activity, using YM-201636, significantly reduces survival primary mouse hippocampal neurons culture. YM-201636 treatment...
Syntaxin1A is organized in nanoclusters that are critical for the docking and priming of secretory vesicles from neurosecretory cells. Whether how these affected by neurotransmitter release nerve terminals a living organism unknown. Here we imaged photoconvertible syntaxin1A-mEos2 motor terminal Drosophila larvae single-particle tracking photoactivation localization microscopy. Opto- thermo-genetic neuronal stimulation increased mobility, reduced size molecular density nanoclusters,...