A5008127321- Cardiac electrophysiology and arrhythmias
- Advanced Fluorescence Microscopy Techniques
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Advanced Electron Microscopy Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Neuroscience and Neural Engineering
- Conducting polymers and applications
- Force Microscopy Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Cell Image Analysis Techniques
- Photoacoustic and Ultrasonic Imaging
- Near-Field Optical Microscopy
- Advanced MRI Techniques and Applications
- Electrochemical Analysis and Applications
- Connexins and lens biology
- Cardiovascular Function and Risk Factors
- Electrochemical sensors and biosensors
- Receptor Mechanisms and Signaling
- Electron Spin Resonance Studies
- Advanced Biosensing Techniques and Applications
- Optical Coherence Tomography Applications
- Integrated Circuits and Semiconductor Failure Analysis
- Lipid Membrane Structure and Behavior
- Biosensors and Analytical Detection
University of Bern
2022-2024
University of Exeter
2014-2023
National Cerebral and Cardiovascular Center
2023
Institute for Research in Biomedicine
2020
Science and Technology Facilities Council
2020
Living Systems (United States)
2018-2019
University of Auckland
2009-2018
MacDiarmid Institute for Advanced Materials and Nanotechnology
2008
St George's, University of London
1997-2001
St George's Hospital
1996-2000
House dust mite (HDM) allergens are important factors in the increasing prevalence of asthma. The lung epithelium forms a barrier that must cross before they can cause sensitization. However, mechanisms involved unknown. Here we show cysteine proteinase allergen Der p 1 from fecal pellets HDM Dermatophagoides pteronyssinus causes disruption intercellular tight junctions (TJs), which principal components epithelial paracellular permeability barrier. In confluent airway cells, led to cleavage...
We have applied an optical super-resolution technique based on single-molecule localization to examine the peripheral distribution of a cardiac signaling protein, ryanodine receptor (RyR), in rat ventricular myocytes. RyRs form clusters with mean size approximately 14 per cluster, which is almost order magnitude smaller than previously estimated. Clusters were typically not circular (as assumed) but elongated average aspect ratio 1.9. Edge-to-edge distances between adjacent RyR often <50...
The neuromuscular junction (NMJ) plays a fundamental role in transferring information from lower motor neuron to skeletal muscle generate movement. It is also an experimentally accessible model synapse routinely studied animal models explore aspects of synaptic form and function. Here, we combined morphological techniques, super-resolution imaging, proteomic profiling reveal the detailed cellular molecular architecture human NMJ. Human NMJs were significantly smaller, less complex, more...
Abstract —The transverse tubular system (t-system) of cardiac muscle is a structure that allows rapid propagation excitation into the cell interior. Using 2-photon molecular microscopy and digital image–processing methods, we have obtained comprehensive overview t-system rat ventricular myocytes in living cells. We show it possible to quantify morphology terms average local tubule diameter, branching pattern, abundance by immersing dextran-linked fluorescein solution. Our data suggest...
A simple DNA sensing platform was developed based on the fluorescence resonance energy transfer (FRET) between blue-luminescent CdTe QDs and dye-labeled ssDNA. cationic polymer acts as a "bridge" to bring donor acceptor together achieves high FRET efficiency. The hybridization event recognized by different efficiencies due interaction abilities of single-stranded double-stranded with polymer. This provides homogeneous assay that takes advantage detection method, but minimal modification.
There have been only a few studies of how allergens cross the airway epithelium to cause allergic sensitization. House dust mite fecal pellets (HDMFP) contain several proteolytic enzymes. Group 1 are cysteine peptidases, whilst those groups 3, 6 and 9 catalytic sites indicative enzymes that mechanistically behave as serine peptidases. We previously shown group allergen Der p leads cleavage tight junctions (TJs), allowing delivery antigen presenting cells. In this study we determined whether...
Background Optical super-resolution imaging of fluorescently stained biological samples is rapidly becoming an important tool to investigate protein distribution at the molecular scale. It therefore develop practical methods that allow capturing full three-dimensional nature systems and also can visualize multiple species in same sample. Methodology/Principal Findings We show use a combination conventional near-infrared dyes, such as Alexa 647, 680 750, all excited with 671 nm diode laser,...
Single rat ventricular myocytes and human ventricle tissue sections were labeled with antibodies against the ryanodine receptor (RyR) alpha-actinin to examine 3D distribution of RyRs confocal microscopy. Image contrast was maximized by refractive index matching deconvolution. The RyR label formed discrete puncta representing clusters or "couplons" around edges myofilaments a nearest-neighbor spacing 0.66 +/- 0.06 microm in 0.78 0.07 human. Each bundle myofibrils served approximately six...
Background The cardiac myocyte t-tubular system ensures rapid, uniform cell activation and several experimental lines of evidence suggest changes in the associated excitation-contraction coupling proteins may occur heart failure. Methods Results organization t-tubules, L-type calcium channels (DHPRs), ryanodine receptors (RyRs) contractile machinery were examined fixed ventricular tissue samples from both normal failing hearts (idiopathic (non-ischemic) dilated cardiomyopathy) using high...
Signaling nanodomains rely on spatial organization of proteins to allow controlled intracellular signaling. Examples include calcium release sites cardiomyocytes where ryanodine receptors (RyRs) are clustered with their molecular partners. Localization microscopy has been crucial visualizing these but limited by brightness markers, restricting the resolution and quantification individual within. Harnessing remarkable localization precision DNA-PAINT (<10 nm), we visualized punctate labeling...
Abstract Localization microscopy techniques based on localizing single fluorophore molecules now routinely achieve accuracies better than 30 nm. Unlike conventional optical microscopies, localization experiments do not generate an image but a list of discrete coordinates estimated positions. Data display and analysis therefore generally require visualization methods that translate the position data into images. Here we investigate properties several widely used show commonly algorithm...
House dust mite allergen Der p 1 is a cysteine peptidase. Previously, we have suggested that the proteolytic activity of this may contribute to asthma by damaging barrier formed airways epithelium.The present study applied novel techniques compare changes in permeability with quantitative events tight junctions (TJs) and desmosomes (DMs) epithelial cells exposed 1.Confluent monolayers Madin-Darby canine kidney (MDCK) 16HBE14o-human bronchial were used as experimental models. Permeability was...
Extracellular ATP has multimodal actions in the cochlea affecting hearing sensitivity. ATP-gated ion channels involved this process were characterized guinea pig cochlea. Voltage-clamped hair cells exhibited a P2 receptor pharmacology compatible with assembly of from P2X 2 subunits. Reverse transcription-PCR experiments confirmed expression 2–1 subunit mRNA isoform sensory epithelium (organ Corti); splice variant that confers desensitization, 2–2 , was predominant expressed by primary...
Tight junctions (TJs) make a vital contribution to the barrier properties of airway lining. Opening TJs, or their frank cleavage, is suspected as pathophysiological event in lung, but research into cellular and molecular mechanisms involved has been impeded by technical limitations available experimental models. The authors have compared two epithelial cell lines derived from bronchial epithelium explore whether these could constitute appropriate tools for study TJ regulation epithelium....
Novel functionalized pyrroles, 3-pyrrolylacrylic acid (PAA), 5-(3-pyrrolyl) 2,4-pentadienoic (PPDA), and 3-pyrrolylpentanoic (PPA) were synthesized used to construct label-free gene sensors based on pyrrole copolymer films. Electrochemical impedance spectroscopy (EIS) was obtain electrical readout from these sensors. Comparison of the performance PPDA-containing that containing (PPA), a similar but with saturated side chain, showed polymers unsaturated chains have superior properties for use...
Therapeutic advances in prevention and treatment of myocardial infarction (MI) have decreased patient mortality increased concern about efficient repair scar formation, processes that are necessary to attenuate complications such as adverse remodelling heart failure. Since the rapid accumulation activity cardiac fibroblasts is critical for proper we hypothesized infarct generated by a cardiac-resident progenitor cell population. We found C57BL/6 mice mesenchymal stem (MSC) population...