A5007592145- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Antimicrobial Peptides and Activities
- Toxin Mechanisms and Immunotoxins
- Venomous Animal Envenomation and Studies
- Insect and Pesticide Research
- Biochemical and Structural Characterization
- Cardiac electrophysiology and arrhythmias
- Neurobiology and Insect Physiology Research
- Heart Failure Treatment and Management
- Ion Channels and Receptors
- Bacillus and Francisella bacterial research
- Bacterial Genetics and Biotechnology
- Cellular transport and secretion
- Nitric Oxide and Endothelin Effects
- Healthcare and Venom Research
- Neuroscience of respiration and sleep
- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Cardiovascular Function and Risk Factors
- Ubiquitin and proteasome pathways
- Chemical Synthesis and Analysis
- Cardiac Ischemia and Reperfusion
- Endoplasmic Reticulum Stress and Disease
- Fluorine in Organic Chemistry
The University of Queensland
2013-2024
ARC Centre of Excellence for Innovations in Peptide and Protein Science
2021-2024
Australian Research Council
2021-2024
Architecture et Fonction des Macromolécules Biologiques
2013-2020
Centre National de la Recherche Scientifique
2013-2020
Aix-Marseille Université
2013-2019
Disulfide-rich peptides are the dominant component of most animal venoms. These have received much attention as leads for development novel therapeutic agents and bioinsecticides because they target a wide range neuronal receptors ion channels with high degree potency selectivity. In addition, their rigid disulfide framework makes them particularly well suited addressing crucial issue in vivo stability. Structural functional characterization these necessitates robust, reliable expression...
Abstract Summary ArachnoServer is a manually curated database that consolidates information on the sequence, structure, function and pharmacology of spider-venom toxins. Although spider venoms are complex chemical arsenals, primary constituents small disulfide-bridged peptides target neuronal ion channels receptors. Due to their high potency selectivity, these have been developed as pharmacological tools, bioinsecticides drug leads. A new version (v3.0) has includes bioinformatics pipeline...
Background: Ischemia–reperfusion injury (IRI) is one of the major risk factors implicated in morbidity and mortality associated with cardiovascular disease. During cardiac ischemia, buildup acidic metabolites results decreased intracellular extracellular pH, which can reach as low 6.0 to 6.5. The resulting tissue acidosis exacerbates ischemic significantly affects function. Methods: We used genetic pharmacologic methods investigate role acid-sensing ion channel 1a (ASIC1a) IRI at cellular...
Munc18-1 and Syntaxin1 are essential proteins for SNARE-mediated neurotransmission. participates in synaptic vesicle fusion via dual roles: as a docking/chaperone protein by binding closed Syntaxin1, that binds SNARE complexes N-peptide dependent manner. The two roles associated with closed–open conformational transition. Here, we show Syntaxin to is not highly selective, suggesting other parts of the complex involved Munc18-1. We also find an N peptide physically anchored C terminus, this...
Acid-sensing ion channel 1a (ASIC1a) is a primary acid sensor in the peripheral and central nervous system. It has been implicated as novel therapeutic target for broad range of pathophysiological conditions including pain, ischemic stroke, depression, autoimmune diseases such multiple sclerosis. The only known selective blocker ASIC1a π-TRTX-Pc1a (PcTx1), disulfide-rich 40-residue peptide isolated from spider venom. an effective analgesic rodent models acute pain it provides neuroprotection...
Disulfide-rich proteins or DRPs are versatile bioactive compounds that encompass a wide variety of pharmacological, therapeutic, and/or biotechnological applications. Still, the production in sufficient quantities is major bottleneck for their complete structural functional characterization. Recombinant expression such small containing multiple disulfide bonds bacteria E. coli considered difficult and general methods protocols, particularly on high throughput scale, limited. Here we report...
Background and Purpose Acid‐sensing ion channels (ASICs) are primary acid sensors in mammals, with the ASIC1b ASIC3 subtypes being involved peripheral nociception. The antiprotozoal drug diminazene is a moderately potent ASIC inhibitor, but its analgesic activity has not been assessed. Experimental Approach We determined subtype selectivity of mechanism by which it inhibits ASICs using voltage‐clamp electrophysiology Xenopus oocytes expressing 1–3. Its was then assessed relative to APETx2,...
Animal venoms are complex molecular cocktails containing a wide range of biologically active disulphide-reticulated peptides that target, with high selectivity and efficacy, variety membrane receptors. Disulphide-reticulated have evolved to display improved specificity, low immunogenicity show much higher resistance degradation than linear peptides. These properties make venom attractive candidates for drug development. However, recombinant expression reticulated disulphide bonds is...
Background and Purpose The spider‐venom peptide PcTx1 is the most potent selective inhibitor of acid‐sensing ion channel (ASIC) 1a. It has centrally acting analgesic activity neuroprotective in rodent models ischaemic stroke. Understanding molecular details : ASIC1a interaction should facilitate development therapeutically useful modulators. Previously, we showed that several key pharmacophore residues reside a dynamic β‐hairpin loop; conclusions confirmed by recent crystal structures...
Venoms are excellent model systems for studying evolutionary processes associated with predator-prey interactions. Here, we present the discovery of a peptide toxin, MIITX2-Mg1a, which is major component venom Australian giant red bull ant Myrmecia gulosa and has evolved to mimic, both structurally functionally, vertebrate epidermal growth factor (EGF) hormones. We show that Mg1a potent agonist mammalian EGF receptor ErbB1, intraplantar injection in mice causes long-lasting hypersensitivity...
Animal venoms are large, complex libraries of bioactive, disulphide-rich peptides. These peptides, and their novel biological activities, increasing pharmacological therapeutic importance. However, recombinant expression venom peptides in Escherichia coli remains difficult due to the significant number cysteine residues requiring effective post-translational processing. There is also an urgent need develop high-throughput protocols applicable production reticulated enable efficient screening...
Journal Article Acid-sensing ion channel 1a blockade reduces myocardial injury in rodent models of infarction Get access Meredith A Redd, Redd Institute for Molecular Bioscience, University Queensland, 306 Carmody Road, St.Lucia, QLD 4072, AustraliaCritical Care Research Group, The Prince Charles Hospital Northside Clinical Unit and Faculty Medicine, Australia Search other works by this author on: Oxford Academic PubMed Google Scholar Yusuke Yoshikawa, Yoshikawa School Biomedical Sciences,...
Escherichia coli (E. coli) is the most widely used expression system for production of recombinant proteins structural and functional studies. However, purifying sometimes challenging since many are expressed in an insoluble form. When working with difficult or multiple targets it therefore recommended to use high throughput (HTP) protein screening on a small scale (1-4 ml cultures) quickly identify conditions soluble expression. To cope various genomics programs lab, quantitative (within...
Animal venoms are rich in hundreds of toxins with extraordinary biological activities. Their exploitation is difficult due to their complexity and the small quantities venom available from most venomous species. We developed a Venomics approach combining transcriptomic proteomic characterization 191 species identified 20,206 toxin sequences. Two complementary production strategies based on solid-phase synthesis recombinant expression Escherichia coli generated physical bank 3597 toxins....
Hi1a is a venom peptide from the Australian funnel-web spider Hadronyche infensa with complex tertiary structure. has neuroprotective and cardioprotective properties due to its potent inhibition of acid-sensing ion channel 1a (ASIC1a) currently being pursued as novel therapy for acute ischemic events. Herein, we describe total synthesis using native chemical ligation. The synthetic was successfully folded exhibited similar inhibitory activity on ASIC1a recombinant Hi1a.
Activation of acid-sensing ion channel 1a (ASIC1a) plays a major role in mediating acidosis-induced neuronal injury following stroke. Therefore, the inhibition ASIC1a is potential therapeutic avenue for treatment Venom-peptide Hi1a, selective and highly potent inhibitor, reduces infarct size functional deficits when injected into brain after stroke rodents. However, its efficacy administered using clinically relevant route administration remains to be established. current investigation aims...
Acid-sensing ion channel 1a (ASIC1a) is a proton-activated that expressed ubiquitously throughout the central nervous system and in various types of immune cells. Its role spinal cord injury (SCI) controversial; inhibition ASIC1a has been reported to improve SCI pathology