A5008609876- Parasitic Infections and Diagnostics
- Retinal Diseases and Treatments
- Biomedical Research and Pathophysiology
- Ocular Disorders and Treatments
- Parasites and Host Interactions
- Amoebic Infections and Treatments
- Retinal Imaging and Analysis
- Helminth infection and control
- Parasite Biology and Host Interactions
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Malaria Research and Control
- RNA regulation and disease
- Retinoids in leukemia and cellular processes
- Glaucoma and retinal disorders
- Evolution and Genetic Dynamics
- Genetic Associations and Epidemiology
- Coccidia and coccidiosis research
- Cytomegalovirus and herpesvirus research
- RNA and protein synthesis mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Epigenetics and DNA Methylation
- Drug Transport and Resistance Mechanisms
- Complement system in diseases
Walter and Eliza Hall Institute of Medical Research
2015-2025
The University of Melbourne
2016-2025
The George Institute for Global Health
2022
Uppsala University
2018
Melbourne Health
2013-2014
Trained immunity describes the capacity of innate immune cells to develop heterologous memory in response certain exogenous exposures. This phenomenon mediates, at least part, beneficial off-target effects BCG vaccine. Using an vitro model trained immunity, we show that exposure induces a persistent change active histone modifications, DNA methylation, transcription, and adenosine-to-inosine RNA modification human monocytes. By profiling methylation circulating monocytes from infants MIS...
Abstract Lucilia cuprina is a parasitic fly of major economic importance worldwide. Larvae this invade their animal host, feed on tissues and excretions progressively cause severe skin disease (myiasis). Here we report the sequence annotation 458-megabase draft genome . Analyses 14,544 predicted protein-encoding genes provide unique insights into fly’s molecular biology, interactions with host insecticide resistance. These have broad implications for designing new methods prevention control myiasis.
Cryptosporidiosis is a leading cause of waterborne diarrheal disease globally and an important contributor to mortality in infants the immunosuppressed. Despite its importance, Cryptosporidium community has only had access good, but incomplete, parvum IOWA reference genome sequence. Incomplete sequences hamper annotation, experimental design, interpretation. We have generated new C. assembly supported by Pacific Biosciences (PacBio) Oxford Nanopore long-read technologies comparative...
Background Whether there are differential effects of first-generation antipsychotics (FGAs) and second-generation (SGAs) on the brain is currently debated. Although some studies report that FGAs reduce grey matter more than SGAs, others do not, research to date limited by a focus schizophrenia spectrum disorders. To address this limitation, study investigated medication in patients being treated for first-episode or affective psychoses. Method Cortical thickness was compared between 52...
Although fascioliasis has been relatively well studied, little is known about the molecular basis of this disease. This particularly relevant, considering very different response that sheep have to Fasciola hepatica relative cattle. The acute phase disease severe in sheep, whereas chronic more common To begin explore host-response and improve understanding host-pathogen interactions during parasite’s migration through liver parenchyma bile duct, we used RNA sequencing (RNA-seq) investigate...
Macular Telangiectasia Type 2 (MacTel) is a rare degenerative retinal disease with complex genetic architecture. We performed genome-wide association study on 1,067 MacTel patients and 3,799 controls, which identified eight novel significant loci (p < 5 × 10-8), confirmed all three previously reported loci. Using MAGMA, eQTL transcriptome-wide analysis, we prioritised 48 genes implicated in serine-glycine biosynthesis, metabolite transport, vasculature thickness. Mendelian randomization...
The most severe form of malaria in humans is caused by the protozoan parasite Plasmodium falciparum. invasive parasites termed a merozoite and it employs an array proteins that bind to host cell mediate invasion. In falciparum, erythrocyte binding-like (EBL) reticulocyte (Rh) protein families are responsible for binding specific receptors invasion mediating signalling events initiate active entry parasite. Here we have addressed role cytoplasmic tails these activating after receptor...
is an intestinal parasite that causes 200-300 million episodes of diarrhoea annually. Metronidazole (Mtz) a front-line anti-giardial, but treatment failure common and clinical resistance has been demonstrated. Mtz thought to be activated within the by oxidoreductase enzymes, kill causing oxidative damage. In
Abstract Background Metronidazole (Mtz) is the frontline drug treatment for multiple anaerobic pathogens, including gastrointestinal protist, Giardia duodenalis. However, failure common and linked to in vivo resistance. In Giardia, vitro drug-resistant lines allow controlled experimental interrogation of resistance mechanisms isogenic cultures. resistance-associated changes are inconsistent between lines, phenotypic data incomplete, rarely genetically fixed, highlighted by reversion...
Abstract Macular Telangiectasia type 2 (MacTel) is an uncommon bilateral retinal disease, in which glial cell and photoreceptor degeneration leads to central vision loss. The causative disease mechanism largely unknown, no treatment currently available. A previous study found variants genes associated with glycine–serine metabolism ( PSPH , PHGDH CPS1 ) be MacTel, showed low levels of glycine serine the serum MacTel patients. Recently, a role deoxysphingolipids has been established. However,...
Objective Dominant spinocerebellar ataxias (SCA) are characterized by genetic heterogeneity. Some mapped and named loci remain without a causal gene identified. Here we applied next generation sequencing (NGS) to uncover the etiology of SCA25 locus . Methods Whole‐exome whole‐genome were performed in families linked , including French family which was originally mapped. Whole exome sequence data interrogated cohort 796 ataxia patients unknown etiology. Results The phenotype spans slowly...
Abstract Retinal thickness is a marker of retinal health and more broadly, seen as promising biomarker for many systemic diseases. measurements are procured from optical coherence tomography (OCT) part routine clinical eyecare. We processed the UK Biobank OCT images using convolutional neural network to produce fine-scale across > 29,000 points in macula, retina responsible human central vision. The macula disproportionately affected by high disease burden disorders such age-related...
Giardia intestinalis is a parasitic protist that causes diarrhea in humans, affecting mainly children of the developing world, elderly and immunocompromised individuals. Humans are infected by two major assemblages (i.e. genetic subtypes), A B, with latter being most common. So far, there little information on molecular or cellular changes during infections assemblage B. Here, we used RNA sequencing to study transcriptional Caco-2 intestinal epithelial cells (IECs) co-incubated B (GS...
Patient-derived induced pluripotent stem cells (iPSCs) provide a powerful tool for identifying cellular and molecular mechanisms of disease. Macular telangiectasia type 2 (MacTel) is rare, late-onset degenerative retinal disease with an extremely heterogeneous genetic architecture, lending itself to the use iPSCs. Whole-exome sequencing screens pedigree analyses have identified rare causative mutations that account less than 5% cases. Metabolomic surveys patient populations GWAS linked...
Metabolic homeostasis is maintained by redundant pathways to ensure adequate nutrient supply during fasting and other stresses. These are regulated locally in tissues systemically via the liver, kidney, circulation. Here, we characterize how serine, glycine, one-carbon (SGOC) metabolism fluxes across eye, kidney sustain retinal amino acid levels function. Individuals with macular telangiectasia (MacTel), an age-related disease reduced circulating serine carrying deleterious alleles SGOC...
Fasciola hepatica is a parasitic trematode that infects wide range of mammalian hosts, including livestock and humans, in temperate tropical regions globally. This causes the disease fascioliasis, which consists an acute phase (≤ 12 weeks) during juvenile parasites migrate through host liver tissues, chronic (> following establishment adult bile ducts. Few studies have explored progression response over course infection same animals. In this study, we characterized transcriptomic changes...
Abstract Routine monitoring of toxic cyanobacteria depends on up-to-date epidemiological information about their distribution. In Australia, anatoxin producing are not regularly tested for and thought to be rare if absent from the continent. Our study investigated presence anatoxin-a (ATX-a) in surface water samples (n = 226 67 sampling locations) collected 2010 2017 across state Victoria, Australia. We (1) detected distribution ana C (anatoxin-a synthetase C) gene sequences previously...
Macular telangiectasia type 2 (MacTel) is a rare, heritable and largely untreatable retinal disorder, often comorbid with diabetes. Genetic risk loci subtend vascular calibre glycine/serine/threonine metabolism genes. Serine deficiency may contribute to MacTel via neurotoxic deoxysphingolipid production; however, an independent contribution also suspected. Here, we use statistical genetics dissect the causal mechanisms underpinning this complex disease.We integrated genetic markers for...
The non-essential amino acids serine, glycine, and alanine, as well diverse sphingolipid species, are implicated in inherited neuro-retinal disorders metabolically linked by serine palmitoyltransferase (SPT), a key enzyme membrane lipid biogenesis. To gain insight into the pathophysiological mechanisms linking these pathways to diseases we compared patients diagnosed with two intertwined diseases: macular telangiectasia type II (MacTel), hereditary sensory autonomic neuropathy 1 (HSAN1), or both.
As a result of limited classes anthelmintics and an over-reliance on chemical control, there is great need to discover new compounds combat drug resistance in parasitic nematodes. Here, we show that deguelin, plant-derived rotenoid, selectively potently inhibits the motility development nematodes, which supports its potential as lead candidate for development. Furthermore, demonstrate deguelin treatment significantly increases gene transcription associated with energy metabolism,...