A5058130238- Streptococcal Infections and Treatments
- Neonatal and Maternal Infections
- Amyotrophic Lateral Sclerosis Research
- Adenosine and Purinergic Signaling
- Antimicrobial Resistance in Staphylococcus
- Inflammasome and immune disorders
- Bacterial Identification and Susceptibility Testing
- Immune Cell Function and Interaction
- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Bartonella species infections research
- RNA Research and Splicing
- Protease and Inhibitor Mechanisms
- Adolescent and Pediatric Healthcare
- Clostridium difficile and Clostridium perfringens research
- Parkinson's Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Gastrointestinal disorders and treatments
- Trace Elements in Health
- Otolaryngology and Infectious Diseases
- Cell Adhesion Molecules Research
- Alzheimer's disease research and treatments
- Microscopic Colitis
- Hematopoietic Stem Cell Transplantation
- RNA regulation and disease
Ontario Genomics
2023
Illawarra Health and Medical Research Institute
2013-2022
University of Wollongong
2013-2021
Abstract The re-emergence of scarlet fever poses a new global public health threat. capacity North-East Asian serotype M12 ( emm 12) Streptococcus pyogenes (group A , GAS) to cause has been linked epidemiologically the presence novel prophages, including prophage ΦHKU.vir encoding secreted superantigens SSA and SpeC DNase Spd1. Here, we report molecular characterization ΦHKU.vir-encoded exotoxins. We demonstrate that streptolysin O (SLO)-induced glutathione efflux from host cellular stores...
Abstract Accurately modeling and predicting RNA biology has been a long-standing challenge, bearing significant clinical ramifications for variant interpretation the formulation of tailored therapeutics. We describe foundation model biology, “BigRNA”, which was trained on thousands genome-matched datasets to predict tissue-specific expression, splicing, microRNA sites, binding protein specificity from DNA sequence. Unlike approaches that are restricted missense variants, BigRNA can identify...
The globally significant human pathogen group A <i>Streptococcus</i> (GAS) sequesters the host protease plasmin to cell surface during invasive disease initiation. Recent evidence has shown that localized activity prevents opsonization of several bacterial species by key components innate immune system in vitro. Here we demonstrate at GAS resulted degradation complement factor C3b, and plasminogen acquisition is associated with a decrease C3b neutrophil-mediated killing...
Abstract Background: Allogeneic haematopoietic stem cell transplantation (HSCT) is a curative therapy for blood cancers; but results in the development of graft-versus-host disease (GVHD) up to 70% recipients. During GVHD, tissue damage ATP release into extracellular compartment activating P2X7 on antigen-presenting cells, leading pro-inflammatory cytokines and subsequent activation donor T cells. Therefore, aim present study was examine murine (m) P2rx7 human (h) P2RX7 gene expression GVHD...
The synthetic copper-containing compound, CuATSM, has emerged as one of the most promising drug candidates developed for treatment amyotrophic lateral sclerosis (ALS). Multiple studies have reported CuATSM provides therapeutic efficacy in various mouse models ALS without any observable adverse effects. Moreover, recent results from an open label clinical study suggested that daily oral dosing with slows disease progression patients both sporadic and familial ALS, providing encouraging...
Abstract Mutant superoxide dismutase 1 (SOD1) can be constitutively released from motor neurons and transmitted to naïve promote the progression of amyotrophic lateral sclerosis (ALS). However, biological impacts this process precise mechanisms SOD1 release remain fully resolved. Using biochemical fluorescent techniques, study aimed determine if P2X7 receptor activation could induce mutant whether or microglia mediate effects associated with neurodegeneration in ALS. Aggregated G93A , murine...
Recruitment of the serine protease plasmin is central to pathogenesis many bacterial species, including Group A streptococcus (GAS), a leading cause morbidity and mortality globally. key process in invasive GAS disease ability accumulate at cell surface, however role host activators plasminogen this poorly understood. Here, we demonstrate for first time that urokinase-type activator (uPA) contributes recruitment subsequent initiation vivo. In absence source activators, streptokinase (Ska)...
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disorder characterized by the degeneration and subsequent loss of upper lower motor neurons, resulting in reduced muscle function paralysis (Mathis et al., 2017). Current therapies are limited to oral administration riluzole, which improves survival only 3 months Thus, new urgently required treat this neurodegenerative disorder. Over past decade, intercellular signaling pathway involving extracellular adenosine triphosphate (ATP)...
Polymorphonuclear leukocyte (PMN) cell death strongly influences the resolution of inflammatory episodes, and may exacerbate adverse pathologies in response to infection. We investigated PMN mechanisms following infection by virulent group A <i>Streptococcus</i> (GAS). Human PMNs were infected vitro with a clinical, GAS isolate an avirulent derivative strain, compared for phagocytosis, production reactive oxygen species (ROS), mitochondrial membrane depolarization apoptotic...
Invasive infections due to group A Streptococcus (GAS) advance rapidly causing tissue degradation and unregulated inflammation. Neutrophils are the primary immune cells that respond GAS. The neutrophil response GAS was characterised in two M1T1 isolates; 5448 animal passaged variant 5448AP. Co-incubation of neutrophils with 5448AP resulted proliferation lowered production reactive oxygen species when compared 5448. Infection both strains invoked death, however apoptosis reduced Both induced...
Plasminogen (Plg) circulates in the host as two predominant glycoforms. Glycoform I Plg (GI-Plg) contains glycosylation sites at Asn289 and Thr346, whereas glycoform II (GII-Plg) is exclusively glycosylated Thr346. Surface plasmon resonance experiments demonstrated that binding group A streptococcal M protein (PAM) exhibits comparative equal affinity for GI- GII-Plg "closed" conformation (for GII-Plg, KD = 27.4 nM; GI-Plg, 37.0 nM). When was "open" conformation, PAM exhibited an 11-fold...
Summary Invasive infections due to Group A Streptococcus (GAS) advance rapidly causing tissue degradation and unregulated inflammation. Neutrophils are the primary immune cells that respond GAS. The neutrophil response GAS was characterised in two M1T1 isolates; 5448 animal passaged variant 5448AP. Neutrophil co-incubation with 5448AP allowed proliferation of while it also lowered production reactive oxygen species by neutrophils when compared 5448. Infection both strains invoked death,...
Abstract The re-emergence of scarlet fever poses a new global public health threat. capacity North-East Asian serotype M12 ( emm 12) Streptococcus pyogenes (group A , GAS) to cause has been linked epidemiologically the presence novel prophages, including prophage ΦHKU.vir encoding secreted superantigens SSA and SpeC DNase Spd1. Here we report comprehensive molecular characterization ΦHKU.vir-encoded exotoxins. We demonstrate that streptolysin O (SLO)-induced glutathione efflux from host...
<title>Abstract</title> Accurately modeling and predicting RNA biology has been a long-standing challenge, bearing significant clinical ramifications for variant interpretation the formulation of tailored therapeutics. We describe foundation model biology, “BigRNA”, which was trained on thousands genome-matched datasets to predict tissue-specific expression, splicing, microRNA sites, binding protein specificity from DNA sequence. Unlike approaches that are restricted missense variants,...