A5049796264- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Cardiovascular Effects of Exercise
- RNA Research and Splicing
- Williams Syndrome Research
- Genetic Neurodegenerative Diseases
- Polymer Surface Interaction Studies
- Nuclear Structure and Function
- Advanced Fluorescence Microscopy Techniques
- Cellular transport and secretion
- Tissue Engineering and Regenerative Medicine
- RNA and protein synthesis mechanisms
- Muscle metabolism and nutrition
- Electrospun Nanofibers in Biomedical Applications
- Cancer Treatment and Pharmacology
- Genetics and Physical Performance
- Cell Adhesion Molecules Research
- Ion channel regulation and function
- 3D Printing in Biomedical Research
- Neurogenetic and Muscular Disorders Research
- Neuroblastoma Research and Treatments
- Advanced Electron Microscopy Techniques and Applications
- Sports Performance and Training
UNSW Sydney
2015-2024
Kensington Health
2024
Cancer Institute of New South Wales
2021
The University of Sydney
1996-2013
Children's Hospital at Westmead
2006-2013
Translational Research Institute
2013
The University of Queensland
2013
Cincinnati Children's Hospital Medical Center
2013
Centenary Institute
2013
Monash University
2013
Heterokaryons provide a model system in which to examine how tissue-specific phenotypes arise and are maintained. When muscle cells fused with nonmuscle cells, gene expression is activated the cell type. Gene was studied either at single level monoclonal antibodies or mass cultures biochemical molecular level. In all of types tested, including representatives different embryonic lineages, phenotypes, developmental stages, induced. Differences among kinetics, frequency, dosage requirements...
A common nonsense polymorphism (R577X) in the ACTN3 gene results complete deficiency of fast skeletal muscle fiber protein α-actinin-3 an estimated one billion humans worldwide. The XX null genotype is under-represented elite sprint athletes, associated with reduced strength and performance non-athletes, over-represented endurance suggesting that increases at cost power generation. Here we report from Actn3 knockout mice displays force generation, consistent human association studies....
The availability of multicopy plasmid vectors for the yeast Saccharomyces cerevisiae allows selective amplification individual segments genome. Increased dosage particular genes results in overproduction specific gene products and thereby confers resistance to certain metabolic inhibitors. Advantage was taken this fact isolate recombinant clones that increase activities enzymes UDP-N-acetylglucosamine-1-P transferase 3-hydroxy-3-methylglutaryl-CoA reductase.
The specific functions of greater than 40 vertebrate nonmuscle tropomyosins (Tms) are poorly understood. In this article we have tested the ability two Tm isoforms, TmBr3 and human homologue Tm5 (hTM5 NM1 ), to regulate actin filament function. We found that these Tms can differentially alter organization, cell size, shape. hTm5 was able recruit myosin II into stress fibers, which resulted in decreased lamellipodia cellular migration. contrast, transfection induced lamellipodial formation,...
We report a novel mechanism of gene regulation in skeletal muscle fibers. Within an individual myofiber nucleus, not all loci are transcriptionally active at given time and regulated independently. This phenomenon is particularly remarkable because the nuclei within share common cytoplasm. Both endogenous muscle-specific housekeeping genes transgenes this manner. Therefore, despite uniform protein composition contractile apparatus along length fiber, that encode structure transcribed...
Dry powder inhalers (DPIs) are increasingly replacing metered dose in elderly chronic obstructive pulmonary disease (COPD) patients. However, most DPIs dependent on inspiratory flow, which is compromised by the ageing process itself. Using in-check dial method, present study compared peak flow (PIF) rates 26 COPD patients and 14 matched control subjects, at a pre-set resistance level of Aeroliser, Diskus Turbuhaler inhalers. It was found that PIF measured method positively correlated with...
Abstract The actin cytoskeleton is a potentially vulnerable property of cancer cells, yet chemotherapeutic targeting attempts have been hampered by unacceptable toxicity. In this study, we shown that it possible to disrupt specific filament populations isoforms tropomyosin, core component filaments, are selectively upregulated in cancers. A novel class anti-tropomyosin compounds has developed preferentially disrupts the tumor impairing both cell motility and viability. Our lead compound,...
Highlights•Live quantification of RhoA activity during development and disease progression•Real-time visualization signaling in normal skin, osteocytes, neutrophils•Monitoring deregulation invasive mammary pancreatic cancers•Longitudinal vivo imaging inhibition using optical windowsSummaryThe small GTPase is involved a variety fundamental processes tissue. Spatiotemporal control thought to govern mechanosensing, growth, motility cells, while its associated with development. Here, we describe...
Three aspects of the regulation human alpha-skeletal actin gene are examined in this study by quantitative analysis transgenic tissues: level expression, tissue specificity, and developmental regulation. Previous vitro vivo studies analyzing 5' end have indicated that tissue-specific expression is promoter based. Transgenic mice were produced carrying either a 9.5-kilobase pair (kb) fragment or deletion construct with 2.2-kb sequences linked to chloramphenicol acetyltransferase reporter...
Abstract We describe a simple culture method for obtaining highly differentiated clonal C2C12 myotubes using feeder layer of confluent fibroblasts, and document the expression contractile protein aspects myofibre morphology this system. Traditional methods collagen‐ or laminin‐coated tissue‐culture plastic typically results in cyclic pattern detachment reformation myotubes, rarely producing mature adult phenotype. co‐culture on fibroblast substratum facilitates sustained resulting sarcomeric...
Four and a half LIM protein 1 (FHL1/SLIM1) is highly expressed in skeletal cardiac muscle; however, the function of FHL1 remains unknown. Yeast two-hybrid screening identified slow type myosin-binding C as an binding partner. Myosin-binding major myosin-associated striated muscle that enhances lateral association stabilization myosin thick filaments regulates actomyosin interactions. The interaction between was confirmed using co-immunoprecipitation recombinant endogenous proteins....
Regulators of skeletal muscle mass are interest, given the morbidity and mortality atrophy myopathy. Four-and-a-half LIM protein 1 (FHL1) is mutated in several human myopathies, including reducing-body myopathy (RBM). The normal function FHL1 how it causes remains unknown. We find that transgenic expression mouse promotes hypertrophy an oxidative fiber-type switch, leading to increased whole-body strength fatigue resistance. Additionally, overexpression enhances myoblast fusion, resulting...
We evaluated the extent to which muscle-specific genes display identical patterns of mRNA accumulation during human myogenesis. Cloned satellite cells isolated from adult skeletal muscle were expanded in culture, and RNA was low- high-confluence fusing cultures over a 15-day time course. The 20 different transcripts compared these samples with that fetal muscle. expression carbonic anhydrase 3, myoglobin, HSP83, mRNAs encoding eight unknown proteins examined myogenic cultures. In general,...
Abstract Changes in the mRNA levels during mammalian myogenesis were compared for seven polypeptides of mitochondrial respiration (the DNA‐encoded cytochrome oxidase subunit III, ATP synthase 6, NADH dehydrogenase subunits 1 and 2, 16S ribosomal RNA; nuclear encoded β adenine nucleotide translocase) three glycolysis (glyceraldehyde‐3‐phosphate dehydrogenase, pyruvate kinase, triose‐phosphate isomerase). Progressive changes conversion from myoblasts to myotubes monitored under both...
E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions cancer can lead to collapse tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mouse enables intravital photobleaching quantification E-cadherin mobility live tissue without affecting normal biology. We demonstrate broad applications this by examining regulation multiple tissues,...
Platelets are anuclear cells that essential for blood clotting. They produced by large polyploid precursor called megakaryocytes. Previous genome-wide association studies in nearly 70,000 individuals indicated single nucleotide variants (SNVs) the gene encoding actin cytoskeletal regulator tropomyosin 4 (TPM4) exert an effect on count and volume of platelets. Platelet number independent risk factors heart attack stroke. Here, we have identified 2 unrelated families BRIDGE Bleeding Disorders...
Abstract Phenotypic plasticity, defined as the ability of individual cells with stable genotypes to exert different phenotypes upon exposure specific environmental cues, represent quintessential hallmark cancer cell en route from primary lesion distant organ sites where metastatic colonization will occur. plasticity is driven by a broad spectrum epigenetic mechanisms that allow for reversibility epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions (EMT/MET). By taking...
Several families of growth factors have been identified as regulators cell fate in the developing lens. Members fibroblast factor family are potent inducers lens fiber differentiation. transforming β (TGFβ) family, particularly bone morphogenetic proteins, also implicated various stages and ocular development, including induction placode formation. However, at later TGFβ members shown to induce pathological changes epithelial cells similar those seen forms human subcapsular cataract....