A5064694971- SARS-CoV-2 and COVID-19 Research
- Cellular transport and secretion
- COVID-19 Clinical Research Studies
- Lipid Membrane Structure and Behavior
- Microtubule and mitosis dynamics
- Advanced Fluorescence Microscopy Techniques
- Hepatitis C virus research
- Alzheimer's disease research and treatments
- Ultrasound and Hyperthermia Applications
- Monoclonal and Polyclonal Antibodies Research
- Advanced Electron Microscopy Techniques and Applications
- Computational Drug Discovery Methods
- Liver Disease Diagnosis and Treatment
- Photoacoustic and Ultrasonic Imaging
- Neuroscience and Neuropharmacology Research
- Systemic Lupus Erythematosus Research
- Viral Infections and Outbreaks Research
- Hepatitis B Virus Studies
- Erythrocyte Function and Pathophysiology
- Ultrasound Imaging and Elastography
- Neuroinflammation and Neurodegeneration Mechanisms
- Telomeres, Telomerase, and Senescence
- Vagus Nerve Stimulation Research
- Circadian rhythm and melatonin
- Receptor Mechanisms and Signaling
The University of Queensland
2016-2025
Park Centre for Mental Health
2018-2025
Allen Institute for Brain Science
2023
Indian Institute of Science Bangalore
2011-2020
The entry of SARS-CoV-2 into target cells requires the activation its surface spike protein, S, by host proteases. serine protease TMPRSS2 and cysteine proteases Cathepsin B/L can activate making two independent pathways accessible to SARS-CoV-2. Blocking prevents in vitro . This blockade may be achieved vivo through ‘repurposing’ drugs, a potential treatment option for COVID-19 that is now clinical trials. Here, we found, surprisingly, drugs targeting pathways, although independent, could...
Aging is a major risk factor for neurodegenerative diseases, and coronavirus disease 2019 (COVID-19) linked to severe neurological manifestations. Senescent cells contribute brain aging, but the impact of virus-induced senescence on neuropathologies unknown. Here we show that senescent accumulate in aged human organoids senolytics reduce age-related inflammation rejuvenate transcriptomic aging clocks. In postmortem brains patients with COVID-19 observed increased cell accumulation compared...
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,...
Our understanding of endocytic pathway dynamics is severely restricted by the diffraction limit light microscopy. To address this, we implemented a novel technique based on subdiffractional tracking internalized molecules (sdTIM). This allowed us to image anti–green fluorescent protein Atto647N-tagged nanobodies trapped in synaptic vesicles (SVs) from live hippocampal nerve terminals expressing vesicle-associated membrane 2 (VAMP2)–pHluorin with 36-nm localization precision. results showed...
Most mammalian neurons have a narrow axon, which constrains the passage of large cargoes such as autophagosomes that can be larger than axon diameter. Radial axonal expansion must therefore occur to ensure efficient trafficking. In this study, we reveal speed various undergoing transport is significantly slower small ones and transit diverse-sized causes an acute, albeit transient, radial expansion, immediately restored by constitutive contractility. Using live super-resolution microscopy,...
The SARS-CoV-2 Omicron variant harbours many mutations in its spike protein compared to the original strain, which may alter ability enter cells, cell tropism, and response interventions blocking virus entry. To elucidate these effects, we developed a mathematical model of entry into target cells applied it analyse recent vitro data. can via two pathways, one using host proteases Cathepsin B/L other protease TMPRSS2. We found enhanced efficiency where strain preferentially used reduced thus...
The Src kinase Fyn plays critical roles in memory formation and Alzheimer’s disease. Its targeting to neuronal dendrites is regulated by Tau via an unknown mechanism. As nanoclustering essential for efficient signaling, we used single-molecule tracking characterize the nanoscale distribution of mouse hippocampal neurons, manipulated expression test whether it controls organization. We found that dendritic exhibits at least three distinct motion states, two them associated with nanodomains....
Significance Proteins moving freely on the plasma membrane can become transiently trapped in functionally essential clusters. This capability is likely to be influenced by subtle conformational states of protein promoting or preventing such confinement. The downside conventional imaging overexpressed tagged proteins that it precludes selective tracking inherently minor albeit conformer populations. Intracellular expression single-chain nanobodies allowed us track endogenous highly specific...
The efficacy of COVID-19 vaccines appears to depend in complex ways on the vaccine dosage and interval between prime boost doses. Unexpectedly, lower dose longer prime-boost intervals have yielded higher efficacies clinical trials. To elucidate origins these effects, we developed a stochastic simulation model germinal center (GC) reaction predicted antibody responses elicited by different vaccination protocols. simulations that could increase selection stringency GCs due reduced antigen...
Maintaining genomic integrity and faithful transmission of genetic information is essential for the survival proliferation cells organisms. DNA damage, which threatens genome, rapidly sensed repaired by mechanisms collectively known as damage response. The RNA demethylase FTO has been implicated in this process; however, underlying mechanism regulates repair remains unclear. Here, we use an unbiased quantitative proteomic approach to identify proximal interactome endogenous protein. Our...
<p>The entry of SARS-CoV-2 into target cells requires the activation its surface spike protein, S, by host proteases. The serine protease TMPRSS2 and cysteine proteases Cathepsin B/L can activate making two independent pathways accessible to SARS-CoV-2. Blocking prevents <i>in vitro</i>. This blockade may be achieved vivo</i> through ‘repurposing’ drugs, a potential treatment option for COVID-19 that is now in clinical trials. Here, we found, surprisingly, drugs...
Interaction between the hepatitis C virus (HCV) envelope protein E2 and host receptor CD81 is essential for HCV entry into target cells. The number of E2-CD81 complexes necessary has remained difficult to estimate experimentally. Using recently developed cell culture systems that allow persistent infection in vitro, dependence kinetics on expression been measured. We reasoned analysis latter experiments using a mathematical model viral may yield estimates entry. Here, we constructed which...
Hepatitis C virus (HCV) entry inhibitors (EIs) act synergistically with drugs targeting other stages of the HCV lifecycle. The origin this synergy remains unknown. Here, we argue that may arise from complementary activities across cell subpopulations expressing different levels receptors. We employ mathematical modeling viral kinetics in vitro , where cells a distribution receptor expression are exposed to or without drugs. independently each cell, as expected absence underlying...
Abstract Tau is a microtubule-associated protein that regulated by post-translational modifications. The most studied of these modifications phosphorylation, which affects Tau’s aggregation and loss- gain-of-functions, including the interaction with microtubules, in Alzheimer’s disease primary tauopathies. However, little known about how phosphorylation state its dynamics organisation at single-molecule level. Here, using quantitative localisation microscopy, we examined mimicking or...
The microtubule-associated protein Tau is a driver of neuronal dysfunction in Alzheimer's disease and other tauopathies. In this process, initially undergoes subtle changes to its abundance, subcellular localisation vast array post-translational modifications including phosphorylation, that progressively result the protein's somatodendritic accumulation dysregulation multiple Tau-dependent cellular processes. Given various loss- gain-of-functions brain-wide proteome characterise tauopathies,...