A5062272188- Venomous Animal Envenomation and Studies
- Ion channel regulation and function
- Antimicrobial Peptides and Activities
- Trypanosoma species research and implications
- Nicotinic Acetylcholine Receptors Study
- Insect and Pesticide Research
- Neurobiology and Insect Physiology Research
- Marine Toxins and Detection Methods
- Biochemical and Structural Characterization
- Genetic Neurodegenerative Diseases
- Insect symbiosis and bacterial influences
- RNA and protein synthesis mechanisms
- Single-cell and spatial transcriptomics
- Mitochondrial Function and Pathology
- Insect Resistance and Genetics
- Nutrition, Genetics, and Disease
- Animal Ecology and Behavior Studies
- Molecular Biology Techniques and Applications
- Mosquito-borne diseases and control
- Spider Taxonomy and Behavior Studies
- Bioactive Compounds and Antitumor Agents
- Beetle Biology and Toxicology Studies
- Microfinance and Financial Inclusion
- Crystal structures of chemical compounds
- Nuclear Receptors and Signaling
Collaborative Research Group
2024
The University of Sydney
2019-2024
Garvan Institute of Medical Research
2018-2022
The University of Queensland
2011-2022
St Vincent's Clinic
2018-2019
UNSW Sydney
2018-2019
University of San Carlos of Guatemala
2008-2009
Significance Six million people die each year from stroke, and 5 survivors are left with a permanent disability. Moreover, the neuronal damage caused by stroke often triggers progressive decline in cognitive function that doubles risk of dementia for survivors. Despite this massive global disease burden, there no approved drugs treating injury to brain oxygen deprivation occurring during an ischemic stroke. The precipitous drop pH resulting activates acid-sensing ion channel 1a. We show...
More than 50 neurological and neuromuscular diseases are caused by short tandem repeat (STR) expansions, with 37 different genes implicated to date. We describe the use of programmable targeted long-read sequencing Oxford Nanopore’s ReadUntil function for parallel genotyping all known neuropathogenic STRs in a single assay. Our approach enables accurate, haplotype-resolved assembly DNA methylation profiling STR sites, from list predetermined candidates. This correctly diagnoses individuals...
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...
Spiders are one of the most successful venomous animals, with more than 48,000 described species. Most spider venoms dominated by cysteine-rich peptides a diverse range pharmacological activities. Some contain thousands unique peptides, but little is known about mechanisms used to generate such complex chemical arsenals. We an integrated transcriptomic, proteomic, and structural biology approach demonstrate that lethal Australian funnel-web produces 33 superfamilies venom proteins....
Despite the staggering diversity of venomous animals, there seems to be remarkable convergence in regard types proteins used as toxin scaffolds. However, our understanding this fascinating area evolution has been hampered by narrow taxonomical range studied, with entire groups animals remaining almost completely unstudied. One such group is centipedes, class Chilopoda, which emerged about 440 Ma and may represent oldest terrestrial lineage next scorpions. Here, we provide first comprehensive...
The amount of regulatory RNA encoded in the genome and extent editing by post-transcriptional deamination adenosine to inosine (A-I) have increased with developmental complexity may be an important factor cognitive evolution animals. newest member A-I family ADAR proteins, vertebrate-specific ADAR3, is highly expressed brain, but its functional significance unknown. In vitro studies suggested that ADAR3 acts as a negative regulator scope underlying mechanisms are also Meta-analysis published...
The deterioration or absence of plaster walls in houses and poor hygienic conditions are the most important risk factors for indoor Triatoma dimidiata infestation Guatemala. A cross-disciplinary study was conducted addressing T. infestation, household hygiene, housing construction. focused on local materials cultural aspects (including gender roles) that could lead to long-term improvements wall new mix developed basis laboratory studies construction recommended by villagers. Four villages...
Spiders have evolved pharmacologically complex venoms that serve to rapidly subdue prey and deter predators. The major toxic factors in most spider are small, disulfide-rich peptides. While there is abundant evidence snake by recruitment of genes encoding normal body proteins followed extensive gene duplication accompanied explosive structural functional diversification, the evolutionary trajectory spider-venom peptides less clear. Here we present a spider-toxin superfamily high degree...
Seventeen variables were evaluated as possible risk factors for the intradomiciliary infestation with Triatoma dimidiata in 644 houses Jutiapa, Guatemala. During 2004 assessed vector presence and hygiene, cluttering, material comfort, construction conditions number of inhabitants, among other factors. Chi-square analysis detected significant associations between eight related to domestic sanitary conditions. Log-linear models showed that regardless age house, odds 4.3 10 times lower a good...
Consistent with their diverse pharmacology, peptides derived from venomous animals have been developed as drugs to treat disorders hypertension, diabetes and chronic pain. Melanoma has a poor prognosis due in part its metastatic capacity, warranting further development of novel targeted therapies. This prompted us examine the anti-melanoma activity spider gomesin (AgGom) gomesin-like homolog (HiGom). AgGom HiGom dose-dependently reduced viability proliferation melanoma cells whereas it had...
Significance The venom of Australian funnel-web spiders contains δ-hexatoxins (δ-HXTXs) that exert fatal neurotoxic effects in humans by inhibiting inactivation voltage-gated sodium channels, but their precise ecological role remains unclear. Sequencing venom-gland transcriptomes from 10 species uncovered 22 δ-HXTXs. Evolutionary analysis revealed extreme conservation these toxins, despite ancient origin. We isolated the lethal δ-HXTX Sydney spider and showed it induces pain mice, suggesting...
A critical hurdle in ant venom proteomic investigations is the lack of databases to comprehensively and specifically identify sequence function proteins peptides. To resolve this, we used gland transcriptomics generate a database that was assign tandem mass spectrometry (MS) fragmentation spectra peptides specific transcripts. This performed alongside shotgun liquid chromatography–mass (LC-MS/MS) analysis confirm these assigned transcripts were expressed as proteins. Through combined...
Australian funnel-web spiders are generally considered the most dangerous in world, with envenomations from Sydney spider Atrax robustus resulting at least 14 human fatalities prior to introduction of an effective anti-venom 1980. The clinical envenomation syndrome bites by is due a single 42-residue peptide known as δ-hexatoxin. This delays inactivation voltage-gated sodium channels, which results spontaneous repetitive firing and prolongation action potentials, thereby causing massive...
Pamphobeteus verdolaga is a recently described Theraphosidae spider from the Andean region of Colombia. Previous reports partially characterized its venom profile. In this study, we conducted detailed analysis that includes reversed-phase high-performance liquid chromatography (rp-HPLC), calcium influx assays, tandem mass spectrometry (tMS/MS), and venom-gland transcriptome. rp-HPLC fractions P. showed activity on CaV2.2, CaV3.2, NaV1.7 ion channels. Active contained several peptides with...
The Tasmanian devil faces extinction due to facial tumour disease (DFTD), a highly transmittable clonal form of cancer without available treatment. In this study, we report the cell-autonomous antiproliferative and cytotoxic activities exhibited by spider peptide gomesin (AgGom) gomesin-like homologue (HiGom) in DFTD cells. Mechanistically, both peptides caused significant reduction at G0/G1 phase, correlation with an augmented expression cell cycle inhibitory proteins p53, p27, p21,...
Most neurodegenerative disorders take decades to develop, and their early detection is challenged by confounding non-pathological ageing processes. Therefore, the discovery of genes molecular pathways in both peripheral brain tissues that are highly predictive disease evolution necessary. To find influence Alzheimer's (AD) Parkinson's (PD) pathogenesis, human RNA-Seq transcriptomic data from Brodmann Area 9 (BA9) dorsolateral prefrontal cortex (DLPFC), whole blood (WB), mononuclear cells...
Australian funnel-web spiders are amongst the most dangerous venomous animals. Their venoms induce potentially deadly symptoms, including hyper- and hypotension, tachycardia, bradycardia pulmonary oedema. Human envenomation is more frequent with ground-dwelling species, infamous Sydney spider (Atrax robustus); although, only two tree-dwelling species severe envenomation. To unravel mechanisms that lead to this stark difference in clinical outcomes, we investigated venom transcriptome...