A5086443313- interferon and immune responses
- SARS-CoV-2 and COVID-19 Research
- Antibiotic Resistance in Bacteria
- Immune Response and Inflammation
- Bacterial Identification and Susceptibility Testing
- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Herpesvirus Infections and Treatments
- COVID-19 Clinical Research Studies
- Genomics and Phylogenetic Studies
- Bacterial Infections and Vaccines
- Cellular transport and secretion
- Cytomegalovirus and herpesvirus research
- PI3K/AKT/mTOR signaling in cancer
- Pneumonia and Respiratory Infections
- COVID-19 epidemiological studies
- Inflammasome and immune disorders
- SARS-CoV-2 detection and testing
- Viral gastroenteritis research and epidemiology
- Gene expression and cancer classification
- Protein Kinase Regulation and GTPase Signaling
- Salmonella and Campylobacter epidemiology
- Animal Virus Infections Studies
- Zoonotic diseases and public health
- Microbial Community Ecology and Physiology
Peter Doherty Institute
2019-2025
The University of Melbourne
2020-2025
Walter and Eliza Hall Institute of Medical Research
2017-2018
Monash University
2006-2016
Aarhus University
2010-2015
Institute for Biomedicine
2012
Gene set scoring provides a useful approach for quantifying concordance between sample transcriptomes and selected molecular signatures. Most methods use information from all samples to score an individual sample, leading unstable scores in small data sets introducing biases composition (e.g. varying numbers of different cancer subtypes). To address these issues, we have developed truly single method, associated R/Bioconductor package singscore ( https://bioconductor.org/packages/singscore...
Abstract Genomic sequencing has significant potential to inform public health management for SARS-CoV-2. Here we report high-throughput genomics SARS-CoV-2, 80% of cases in Victoria, Australia (population 6.24 million) between 6 January and 14 April 2020 (total 1,333 COVID-19 cases). We integrate epidemiological, genomic phylodynamic data identify clusters impact interventions. The global diversity SARS-CoV-2 is represented, consistent with multiple importations. Seventy-six distinct were...
Realising the promise of genomics to revolutionise identification and surveillance antimicrobial resistance (AMR) has been a long-standing challenge in clinical public health microbiology. Here, we report creation validation abritAMR, an ISO-certified bioinformatics platform for genomics-based bacterial AMR gene detection. The abritAMR utilises NCBI's AMRFinderPlus, as well additional features that classify determinants into antibiotic classes provide customised reports. We validate by...
Abstract Genomics is a cornerstone of modern pathogen epidemiology yet demonstrating transmission in One Health context challenging, as strains circulate and evolve within between diverse hosts environments. To identify phylogenetic linkages better define relevant measures genomic relatedness context, we collated 5471 Escherichia coli genome sequences from Australia originating humans ( n = 2996), wild animals 870), livestock 649), companion 375), environmental sources 292) food 289)...
The innate immune system is important for control of infections, including herpesvirus infections. Intracellular DNA potently stimulates antiviral IFN responses. It known that plasmacytoid dendritic cells sense in endosomes via TLR9 and nonimmune tissue can the nucleus. However, it remains unknown how where myeloid cells, such as macrophages conventional detect infections with herpesviruses. In this study, we demonstrate HSV-1 capsid was ubiquitinated cytosol degraded by proteasome, hence...
Herpes simplex viruses (HSVs) are highly prevalent neurotropic viruses. While they can replicate lytically in cells of the epithelial lineage, causing lesions on mucocutaneous surfaces, HSVs also establish latent infections neurons, which act as reservoirs virus for subsequent reactivation events. Immunological control HSV involves activation innate immune pattern-recognition receptors such TLR3, detects double-stranded RNA and induces type I IFN expression. Humans with defects TLR3/IFN...
Innate recognition of viruses is mediated by pattern receptors (PRRs) triggering expression antiviral interferons (IFNs) and proinflammatory cytokines. In mice, Toll-like receptor 2 (TLR2) TLR9 as well intracellular nucleotide-sensing pathways have been shown to recognize herpes simplex virus (HSV). Here, we describe how human primary macrophages early HSV infection via pathways. A number inflammatory cytokines, IFNs, IFN-stimulated genes were upregulated after infection. We show that...
Background Innate immune responses have recently been appreciated to play an important role in the pathogenesis of HIV infection. Whereas inadequate innate sensing during acute infection may contribute failure control and eradicate infection, persistent inflammatory later driving chronic activation development immunodeficiency. However, knowledge on specific PAMPs cellular PRRs responsible for inducing remains sparse. Methods/Principal Findings Here we demonstrate a major RIG-I adaptor...
The innate immune response constitutes the first line of defense against infections. Pattern recognition receptors recognize pathogen structures and trigger intracellular signaling pathways leading to cytokine chemokine expression. Reactive oxygen species (ROS) are emerging as an important regulator some these pathways. ROS directly interact with components or induce other post-translational modifications such S-glutathionylation, thereby altering target function. Applying live microscopy,...
Human ciliopathies, including Joubert syndrome (JBTS), arise from cilia dysfunction. The inositol polyphosphate 5-phosphatase INPP5E localizes to and is mutated in JBTS. Murine Inpp5e ablation embryonically lethal recapitulates JBTS, neural tube defects polydactyly; however, the underlying signaling function of at are still emerging. We report Inpp5e−/− embryos exhibit aberrant Hedgehog-dependent patterning with reduced Hedgehog signaling. Using mouse genetics, we show increasing via...
Abstract Vancomycin-resistant Enterococcus faecium (VREfm) is a major nosocomial pathogen. Identifying VREfm transmission dynamics permits targeted interventions, and while genomics increasingly being utilised, methods are not yet standardised or optimised for accuracy. We aimed to develop standardized genomic method identifying putative links. Using comprehensive epidemiological data from cohort of 308 infection colonization cases, we compared multiple approaches quantifying genetic...
The 2'-5' oligoadenylate synthetase (OAS) proteins are traditionally considered intracellular antiviral proteins. However, several studies demonstrate a correlation between the concentration of freely circulating OAS protein in sera from hepatitis C patients and their clinical prognosis. Here we that extracellular OAS1 enters into cells possesses strong activity, both vitro vivo, which is independent RNase L. directly inhibits viral proliferation does not require activation known signaling...
Autophagy has been established as a player in host defense against viruses. The mechanisms by which the induces autophagy during infection are diverse. In case of HSV type 1 (HSV-1), dsRNA-dependent protein kinase is essential for induction fibroblasts through phosphorylation eukaryotic initiation factor 2α (eIF2α). HSV-1 counteracts via ICP34.5, dephosphorylates eIF2α and inhibits Beclin 1. Investigation largely conducted permissive cells, but recent work suggests existence...
Herpesviruses are DNA viruses harboring the capacity to establish lifelong latent-recurrent infections. There is limited knowledge about targeting innate DNA-sensing pathway, as well how system impacts on latent reservoir of herpesvirus In this article, we report that murine gammaherpesvirus 68 (MHV68), in contrast α- and β-herpesviruses, induces very immune responses through DNA-stimulated pathways, which correspondingly played only a minor role control MHV68 infections vivo. Similarly,...
Pyrazinamide plays an important role in tuberculosis treatment; however, its use is complicated by side-effects and challenges with reliable drug susceptibility testing. Resistance to pyrazinamide largely driven mutations pyrazinamidase (pncA), responsible for activation, but genetic heterogeneity has hindered development of a molecular diagnostic test. We proposed information on how variants were likely affect the 3D structure pncA identify lead resistance. curated 610 high confidence...
In Australia, cases of shigellosis usually occur in returned travelers from regions endemicity or men who have sex with men. Resistance to multiple antibiotics has significantly increased Shigella sonnei isolates and represents a significant public health concern. We investigate an outbreak multidrug-resistant S. Victoria, Australia. undertook whole-genome sequencing 54 extended-spectrum-beta-lactamase (ESBL)-producing received at the Microbiological Diagnostic Unit Public Health Laboratory...
BACKGROUND: Whole-genome sequencing of pathogens can improve resolution outbreak clusters and define possible transmission networks. We applied high-throughput genome SARS-CoV-2 to 75% cases in the State Victoria (population 6.24 million) Australia. METHODS: Cases infection were detected through active case finding contact tracing. A dedicated multidisciplinary genomic response team was formed enable rapid integration epidemiological data. Phylodynamic analysis performed assess putative...