- Pancreatic function and diabetes
- Diabetes and associated disorders
- Advanced Glycation End Products research
- Pediatric health and respiratory diseases
- Metabolism, Diabetes, and Cancer
- Immune Response and Inflammation
- Cellular Mechanics and Interactions
- Hippo pathway signaling and YAP/TAZ
- Prion Diseases and Protein Misfolding
- 3D Printing in Biomedical Research
- Asthma and respiratory diseases
- Microfluidic and Capillary Electrophoresis Applications
- Erythrocyte Function and Pathophysiology
- Calcium signaling and nucleotide metabolism
- Genetic and Kidney Cyst Diseases
- Cell Adhesion Molecules Research
- Nanofabrication and Lithography Techniques
- Skin and Cellular Biology Research
- Photosynthetic Processes and Mechanisms
- Pancreatitis Pathology and Treatment
- Diabetes Management and Research
- Adenosine and Purinergic Signaling
- Cellular transport and secretion
- Neonatal Respiratory Health Research
- Genetics and Neurodevelopmental Disorders
The University of Queensland
2012-2024
The University of Sydney
2016-2022
Harry Perkins Institute of Medical Research
2022
Temasek Life Sciences Laboratory
2021
National University of Singapore
2021
Cooperative Trials Group for Neuro-Oncology
2020
The structural organisation of pancreatic β-cells in the islets Langerhans is relatively unknown. Here, using three-dimensional (3D) two-photon, 3D confocal and block-face serial electron microscopy, we demonstrate a consistent situ polarisation define three distinct cell surface domains. An apical domain located at vascular apogee β-cells, defined by location PAR-3 (also known as PARD3) ZO-1 TJP1), delineates an extracellular space into which adjacent project their primary cilia. A separate...
We set out to test the hypothesis that insulin secretion from beta cells is targeted towards vasculature. The spatial location of granule fusion was identified by live-cell two-photon imaging mouse pancreatic within intact islets, using sulforhodamine B labelling. Three-dimensional (3D) immunofluorescence slices used identify proteins associated with neuronal synapses. demonstrated an asymmetric, non-random, distribution sites in response glucose and focal targeting cell membrane facing 3D...
The extracellular matrix (ECM) critically affects β cell functions via integrin activation. But whether these ECM actions drive the spatial organization of cells, as they do in epithelial is unknown. Here, we show that within islets Langerhans, focal adhesion activation cells occurs exclusively where contact capillary (vascular face). In cultured 3D mapping shows enriched insulin granule fusion ECM-coated coverslips, which depends on β1 receptor Culture micro-contact printed stripes...
Abstract Aims/hypothesis We hypothesised that human beta cells are structurally and functional polarised with respect to the islet capillaries. set out test this using confocal microscopy map 3D spatial arrangement of key proteins live-cell imaging determine distribution insulin granule fusion around cells. Methods Human pancreas samples were rapidly fixed processed pancreatic slice technique, which maintains structure architecture. Slices stained immunofluorescence for polarity markers...
Type-2 immunity elicits tissue repair and homeostasis, however dysregulated type-2 responses cause aberrant remodelling, as observed in asthma. Severe respiratory viral infections infancy predispose to later asthma, however, the processes that mediate damage-induced inflammation origins of airway remodelling remain ill-defined. Here, using a preclinical mouse model bronchiolitis, we find increased epithelial mesenchymal high-mobility group box 1 (HMGB1) expression is associated with numbers...
A developing understanding suggests that spatial compartmentalisation in pancreatic β cells is critical controlling insulin secretion. To investigate the mechanisms, we have developed live-cell subcellular imaging methods using mouse organotypic slice. We demonstrate slice, when compared with isolated islets, preserves intact β-cell structure, and enhances glucose-dependent Ca 2+ responses Using slice technique, discovered essential role of local activation integrins downstream component,...
Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, number of individuals paucigranulocytic asthma, which occurs in the absence eosinophilia or neutrophilia. The aetiology unknown. However, both respiratory syncytial virus (RSV) infection and mutations receptor for advanced glycation endproducts (RAGE) are risk factors development. Here, we show that RAGE deficiency impairs anti-viral immunity during an early-life...
Multiprotein micropatterning allows the creation of complex, controlled microenvironments for single cells that can be used study localized effects various proteins and signals on cell survival, development, functions. To enable analysis interactions with microprinted proteins, multiprotein micropattern must have low cross-contamination high long-term stability in a culture medium. achieve this, we employed an optimized plasma ion immersion implantation (PIII) treatment to provide...
ABSTRACT Tissue tension encompasses the mechanical forces exerted on solid tissues within animal bodies, originating from various sources such as cellular contractility, interactions with neighbouring cells and extracellular matrix. Emerging evidence indicates that an imbalance in tissue can influence structural organisation, homeostasis potentially contribute to disease. For instance, heightened impede apical cell extrusion, leading retention of apoptotic or transformed cells. In this...
Abstract Tissue tension encompasses the mechanical forces exerted on solid tissues within animal bodies, originating from various sources such as cellular contractility, interactions with neighboring cells and extracellular matrix. Emerging evidence indicates that an imbalance in can influence structural organization, homeostasis, potentially contribute to disease. For instance, heightened tissue impede apical cell extrusion, leading retention of apoptotic or transformed cells. In this...
The extracellular matrix (ECM) in the islets of Langerhans critically affects ß cell functions via integrin activation. But, whether these ECM actions depend on driving spatial organisation cells, as they do epithelial is unknown. Here, we show that situ, within Langerhans, focal adhesion activation cells occurs exclusively where contact capillary (vascular face). In cultured 3D mapping shows enriched insulin granule fusion proteins. Targeting depends ß1 receptors and kinase. Cell culture...
Abstract A developing understanding suggests that spatial compartmentalisation of components the glucose stimulus-secretion pathway in pancreatic β cells are critical controlling insulin secretion. To investigate mechanisms, we have developed live-cell sub-cellular imaging methods using organotypic slice. We demonstrate slice, when compared with isolated islets, preserves intact cell structure, and enhances dependent Ca 2+ responses Using slice technique, discovered essential role local...