A5047874479- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Mosquito-borne diseases and control
- Insect symbiosis and bacterial influences
- Long-Term Effects of COVID-19
- Insect and Pesticide Research
- Invertebrate Immune Response Mechanisms
- Viral Infections and Vectors
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Microplastics and Plastic Pollution
- ATP Synthase and ATPases Research
- Biochemical and Molecular Research
- Nutrition and Health in Aging
- Insect-Plant Interactions and Control
- Phagocytosis and Immune Regulation
- Iron Metabolism and Disorders
- Ubiquitin and proteasome pathways
- Advancements in Semiconductor Devices and Circuit Design
- interferon and immune responses
- CRISPR and Genetic Engineering
- Nanoparticles: synthesis and applications
- Multiple Sclerosis Research Studies
- Autophagy in Disease and Therapy
- Antimicrobial agents and applications
QIMR Berghofer Medical Research Institute
2020-2024
The University of Queensland
2018-2023
Global microplastic (MP) contamination and the effects on environment are well described. However, potential for MP consumption to affect human health remains controversial. Mice consuming ≈80 μg/kg/day of 1 μm polystyrene MPs via their drinking water showed no weight loss, nor were detected in internal organs. The microbiome was also not significantly changed. did lead small transcriptional changes colon suggesting plasma membrane perturbations mild inflammation. challenged with...
Human
SARS-CoV-2 uses the human ACE2 (hACE2) receptor for cell attachment and entry, with mouse (mACE2) unable to support infection. Herein we describe an ACE2-lentivirus system illustrate its utility in vitro vivo infection models. Transduction of non-permissive lines hACE2 imparted replication competence, transduction mACE2 containing N30D, N31K, F83Y H353K substitutions, match hACE2, rescued replication. Intrapulmonary hACE2-lentivirus C57BL/6J mice permitted significant virus lung epithelium....
How well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified various settings. Herein we use RNA-Seq data bioinformatics approaches to analyze responses SARS-CoV-2 infected lungs, comparing 4 human studies widely used K18-hACE2 model, a model where hACE2 is expressed from ACE2 promoter, that uses adapted virus wild-type mice. Overlap of single copy orthologue differentially genes (scoDEGs) between was...
Granzyme A (GZMA) is a serine protease secreted by cytotoxic lymphocytes, with Gzma -/- mouse studies having informed our understanding of GZMA’s physiological function. We show herein that mice have mixed C57BL/6J and C57BL/6N genetic background retain the full-length nicotinamide nucleotide transhydrogenase ( Nnt ) gene, whereas truncated in mice. Chikungunya viral arthritis was substantially ameliorated mice; however, presence background, rather than loss GZMA expression, responsible for...
Self-amplifying mRNA (SAM) vaccines can be rapidly deployed in the event of disease outbreaks. A legitimate safety concern is potential for recombination between alphavirus-based SAM and circulating viruses. This theoretical risk needs to assessed regulatory process vaccine approval. Herein, we undertake extensive vitro vivo assessments explore a wide selection alphaviruses coronavirus. were found effectively limit alphavirus co-infection through superinfection exclusion, although some...
Warmer climatic conditions have been associated with fewer COVID-19 cases. Herein we infected K18-hACE2 mice housed at the standard animal house temperature of ∼22 °C, or ∼31 which is considered to be thermoneutral for mice. On day 2 post infection, RNA-Seq analyses showed no significant differential gene expression lung in lungs two temperatures, almost identical viral loads and type I interferon responses. There was also difference on 5, but histology clearly elevated inflammatory...
Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which can result in disease, often characterised by a ‘cytokine storm’ and the associated distress syndrome. However, many infections with SARS-CoV-2 are mild or asymptomatic throughout course of infection. Although blood biomarkers disease well studied, less understood inflammatory signatures lung tissues silent infections, wherein infection inflammation rapidly resolved...
The Aedes aegypti mosquito is the primary vector of several medically important arboviruses. endosymbiotic bacterium, Wolbachia pipientis, has emerged as a means blocking transmission arboviruses such dengue and Zika viruses. One strain that shown potential in field trials wAlbB, naturally occurring Asian tiger albopictus. When transinfected into Ae. aegypti, wAlbB exhibits strong virus inhibition. In addition to modulating arboviruses, also modulates some insect-specific Here, we explored...
SUMMARY Background Human infections with Japanese encephalitis virus (JEV) are a leading cause of viral encephalitis. An unprecedented outbreak JEV genotype 4 was recently reported in Australia, an isolate (JEV NSW/22 ) obtained from stillborn piglet brain. Methods Herein we compared the neuropathology , FU (genotype 2) and Nakayama 3) adult C57BL/6J wild-type mice, mice deficient interferon regulatory factor 7 ( Irf7 -/- ), type I receptor Ifnar as well human cortical brain organoids...
ABSTRACT Angiotensin converting enzyme 2 (ACE2) serves as the primary entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV-2). However, ACE2-independent has been observed in vitro SARS-CoV-2 strains containing E484D amino acid substitution spike protein. In this study, we conducted a whole genome CRISPR-Cas9 knockout screen using strain spike-E484D (SARS-CoV-2 MA1 ) to identify mechanisms. Our findings revealed that infection HEK293T cells relied on heparan sulfate and...
The severity of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often dictated a range comorbidities. A considerable literature suggests iron deficiency and overload may contribute to increased infection, inflammation severity, although direct causal relationships have been difficult establish.
ABSTRACT BACKGROUND How well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified various settings. The K18-hACE2 model has been widely used for evaluation of new interventions COVID-19. METHOD Herein we use RNA-Seq data bioinformatics approaches to compare responses SARS-CoV-2 infected lungs mice those humans. RESULTS Overlap differentially expressed genes was generally poor (≈20-30%), even when multiple...
Abstract The mosquito Aedes aegypti is the primary vector of a range medically important viruses including dengue, Zika, West Nile, yellow fever, and chikungunya viruses. endosymbiotic bacterium Wolbachia pipientis w AlbB strain promising biocontrol agent for blocking viral transmission by Ae. . To predict long-term efficacy field applications, thorough understanding interactions between symbiont, host, pathogen required. influences host physiology in variety ways reproduction, immunity,...
Aedes aegypti is a vector of several pathogenic viruses, including dengue, Zika, chikungunya, and yellow fever which are importance to human health. Wolbachia an endosymbiotic bacterium currently used in transinfected mosquitoes suppress replication transmission dengue viruses. However, the mechanism -mediated virus inhibition not fully understood.
Abstract 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 remains controversial. We show that a isolate was significantly more pathogenic in K18-hACE2 mice than isolate, with infections showing increased neuroinvasiveness, resulting brain infection and mortality, similar seen original ancestral isolates. also infected human cortical organoids greater extent In brains...
An adult wild-type C57BL/6J mouse model of chikungunya virus (CHIKV) infection and disease has been extensively used to study the alphaviral arthritic immunopathology evaluate new interventions. How well models recapitulate gene expression profiles seen in humans remains controversial. Herein we perform a comparative transcriptomics analysis using RNA-Seq datasets from CHIKV with obtained adults children acutely infected CHIKV. Despite sampling quite different tissues, peripheral blood feet...
ABSTRACT SARS-CoV-2 uses the human ACE2 (hACE2) receptor for cell attachment and entry, with mouse (mACE2) unable to support infection. Herein we describe an ACE2-lentivirus system illustrate its utility in vitro vivo infection models. Transduction of non-permissive lines hACE2 imparted replication competence, transduction mACE2 containing N30D, N31K, F83Y H353K substitutions, match hACE2, rescued replication. Intranasal hACE2-lentivirus C57BL/6J mice permitted significant virus lungs....
SUMMARY 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 neuroinvasiveness, resulting fulminant brain infection mortality, similar seen original ancestral isolates. also infected human cortical organoids greater extent In brains mice,...
Abstract Presently, no approved antiviral drug targets dengue virus (DENV) infection. Treatment mainly relies on supportive measures, while DENV vaccines’ efficacy varies based factors like vaccine type, circulating serotypes and vaccinated population. This study explores using defective interfering particles (DIPs) lipid nanoparticles (LNPs) to deliver an anti-DENV RNA, known as DI290. Results showed that both DIPs DI290 loaded LNPs (LNP-290) effectively suppressed infection in human...
Abstract The severity of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often dictated a range comorbidities. A considerable literature suggests iron deficiency and overload may contribute to increased infection, inflammation severity, although direct causal relationships have been difficult establish. Here we generate deficient loaded C57BL/6J mice feeding low high diets, with on normal diet representing controls. All were...
Angiotensin converting enzyme 2 (ACE2) serves as the primary entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV-2). However, ACE2-independent has been observed in vitro SARS-CoV-2 strains containing E484D amino acid substitution spike protein. Herein, we conducted a whole genome CRISPR-Cas9 knockout screen using strain spike-E484D (SARS-CoV-2MA1) to identify mechanisms. Our findings revealed that SARS-CoV-2MA1 infection HEK293T cells relied on heparan sulfate and...
ABSTRACT N-linked glycosylation of flavivirus envelope proteins is widely viewed as a requirement for optimal folding, processing and/or transit proteins, and the assembling virons, through endoplasmic reticulum (ER) Golgi. Herein we show that serial passage ZIKV Natal in Rag1 -/- mice generated two unique glycan-deficient mutants, ZIKV-V153D ZIKV-N154D, that, surprisingly, produced titers ∼1 to 2.6 logs higher than glycosylated parental Vero E6 cells human brain organoids. RNA-Seq infected...