Dr Izzy Jayasinghe
School of Biosciences
Full contact details
School of Biosciences
- 2020-present– UKRI Future Leader Fellow, School of Biosciences, University of Sheffield, UK
- 2015-2020 – Lecturer in Cardiovascular Sciences, Faculty of Biological Sciences, University of Leeds, UK
- 2013-2015 – Associate Research Fellow, College of Engineering, Mathematics and Physical Sciences, University of Exeter, UK
- 2011-2013 – Post-doctoral Research Fellow, School of Biomedical Sciences, University of Queensland, Australia
- 2010-2011 – Assistant Research Fellow, Department of Physiology, University of Auckland, New Zealand
- 2007-2010 – PhD, Department of Physiology, University of Auckland, New Zealand
- Research interests
Bursts of intracellular calcium released from subcellular membrane compartments are a form of fast second messenger signaling mechanisms which control a range of cellular processes.
Such processes include the muscle contraction which governs the heartbeat, breathing and movement, downstream gene transcription and mobilization of secretory vesicular stores.
The temporal and spatial patterns of calcium release provide important contextual information to the target(s) of the signal. These are often provided by the organization, the regulation and interplay between the intracellular calcium release channels within these cells.
The most common types include the giant ryanodine receptors (RyRs) and the inositol triphosphate receptors (IP3Rs). As a cell biologist, I am interested in how the spatial organization and biochemical (post-translational) modification of these calcium handling proteins determine the calcium signals which can be observed within a range of cell types.
I use a combination of super-resolution imaging and live cell imaging modalities to interrogate how the cytoplasmic calcium signals may be spatially encoded in the way the sub-cellular ultrastructures are organized.
A key enabler of the visualisation of sub-cellular structures such as protein clusters and organelles is super-resolution microscopy. These imaging modalities include deterministic techniques (such as STED, GSD and SIM) and the more widely used stochastic techniques (PALM, STORM, PAINT).
I am interested in both refining and inventing stochastic super-resolution techniques which enable better study of the structural correlates of cellular signaling.
I am also interested in the newer, and more unconventional super-resolution techniques such as Expansion Microscopy which allow us to physically inflate the cells and tissues in order to resolve the finer sub-structures within them.
New developments in super-resolution microscopy include innovations in the photonics (optical elements of the imaging systems), phononics (the physical properties of the lattice materials used for them), organic and redox chemistries of the fluorescent molecules which allow the localisation of these cellular structures.
One of the primary foci of my current work includes the integration of these innovations to develop cheaper, more versatile and more portable super-resolution instruments and protocols which are more accessible to the users more further afield in the Life Sciences (e.g. clinical, ecological and field scientists).
This person does not have any publications available.
- Conversations with LGBT+ scientists about visibility, leadership and climbing the career ladder. Journal of Cell Science, 135(4).
- STEM Pride: Perspectives from transgender, nonbinary, and genderqueer scientists. Cell, 184(13), 3352-3355.
- A correlative super-resolution protocol to visualise structural underpinnings of fast second-messenger signalling in primary cell types. Methods.
- Multi-scale approaches for the simulation of cardiac electrophysiology: I – sub-cellular and stochastic calcium dynamics from cell to organ. Methods. View this article in WRRO
- Rab46 integrates Ca2+ and histamine signaling to regulate selective cargo release from Weibel-Palade bodies. Journal of Cell Biology, 218(7), 2232-2246. View this article in WRRO
- Three-dimensional and chemical mapping of intracellular signaling nanodomains in health and disease with enhanced expansion microscopy. ACS Nano, 13(2), 2143-2157. View this article in WRRO
- Shining new light on the structural determinants of cardiac couplon function : insights from ten years of nanoscale microscopy. Frontiers in Physiology, 9.
- True molecular scale visualization of variable clustering properties of ryanodine receptors. Cell Reports, 22(2), 557-567. View this article in WRRO
- Transverse tubule remodelling: a cellular pathology driven by both sides of the plasmalemma?. Biophysical Reviews, 9(6), 919-929. View this article in WRRO
- Algorithmic corrections for localization microscopy with sCMOS cameras - characterisation of a computationally efficient localization approach. Optics Express, 25(10), 11701-11716. View this article in WRRO
- Human skeletal muscle plasmalemma alters its structure to change its Ca2+-handling following heavy-load resistance exercise. Nature Communications, 8(1). View this article in WRRO
- Junctophilin-2 in the nanoscale organisation and functional signalling of ryanodine receptor clusters in cardiomyocytes. Journal of Cell Science, 129(23), 4388-4398. View this article in WRRO
- Combining confocal and single molecule localisation microscopy: A correlative approach to multi-scale tissue imaging. Methods, 88, 98-108.
- Nanoscale analysis of ryanodine receptor clusters in dyadic couplings of rat cardiac myocytes. Journal of Molecular and Cellular Cardiology, 80, 45-55.
- Observation of the molecular organization of calcium release sites in fast- and slow-twitch skeletal muscle with nanoscale imaging. Journal of The Royal Society Interface, 11(99), 20140570-20140570.
- Super-resolution fluorescence imaging to study cardiac biophysics: α-actinin distribution and Z-disk topologies in optically thick cardiac tissue slices. Progress in Biophysics and Molecular Biology, 115(2-3), 328-339.
- Three-dimensional reconstruction and analysis of the tubular system of vertebrate skeletal muscle. Journal of Cell Science, 126(17), 4048-4058.
- Examination of the Subsarcolemmal Tubular System of Mammalian Skeletal Muscle Fibers. Biophysical Journal, 104(11), L19-L21.
- Comparison of the organization of t-tubules, sarcoplasmic reticulum and ryanodine receptors in rat and human ventricular myocardium. Clinical and Experimental Pharmacology and Physiology, 39(5), 469-476.
- Nanoscale Organization of Junctophilin-2 and Ryanodine Receptors within Peripheral Couplings of Rat Ventricular Cardiomyocytes. Biophysical Journal, 102(5), L19-L21.
- A new twist in cardiac muscle: dislocated and helicoid arrangements of myofibrillar z-disks in mammalian ventricular myocytes. Journal of Molecular and Cellular Cardiology, 48(5), 964-971.
- Optical single-channel resolution imaging of the ryanodine receptor distribution in rat cardiac myocytes. Proceedings of the National Academy of Sciences, 106(52), 22275-22280.
- Organization of Ryanodine Receptors, Transverse Tubules, and Sodium-Calcium Exchanger in Rat Myocytes. Biophysical Journal, 97(10), 2664-2673.
- Three-dimensional high-resolution imaging of cardiac proteins to construct models of intracellular Ca2+signalling in rat ventricular myocytes. Experimental Physiology, 94(5), 496-508.
- Light-Induced Dark States of Organic Fluochromes Enable 30 nm Resolution Imaging in Standard Media. Biophysical Journal, 96(2), L22-L24.
- 3D visualisation of the cardiac ryanodine receptor clusters and the molecular-scale fraying of dyads. Philosophical transactions of the Royal Society of London. Series B, Biological sciences.
- Right-ventricular heart failure increases spatial heterogeneity in the sub-cellular expression of SERCA2a, reducing calcium-induced-calcium-release, increasing inter-cellular variability, and modulating vulnerability to pro-arrhythmogenic cellular phenomena. Philosophical transactions of the Royal Society of London. Series B, Biological sciences.
- Molecular-scale 3D visualisation of the cardiac ryanodine receptor clusters and the molecular-scale fraying of dyads.
- Revealing t-tubules in striated muscle with new optical super-resolution microscopy techniques. European Journal of Translational Myology, 25(1), 15-15.
- Self-activated photoblinking of nitrogen vacancy centers in nanodiamonds (sandSTORM): A method for rapid single molecule localization microscopy with unlimited observation time.
- 4D Super-Resolution Microscopy with Conventional Fluorophores and Single Wavelength Excitation in Optically Thick Cells and Tissues. PLoS ONE, 6(5), e20645-e20645.
- Peptide ligands of the cardiac ryanodine receptor as super-resolution imaging probes.
- Enhanced expansion microscopy to measure nanoscale structural and biochemical remodeling in single cells, Methods in Cell Biology (pp. 147-180). Elsevier
- Quantitative Super-Resolution Microscopy of Cardiomyocytes, Microscopy of the Heart (pp. 37-73).
- Advances in the Visualization of Molecular Assemblies Within Cellular Signaling Nanodomains: Insights From a Decade of Mapping of Ryanodine Receptor Clusters, Advances in Biomembranes and Lipid Self-Assembly (pp. 167-197). Elsevier View this article in WRRO
- Correlative Single-Molecule Localization Microscopy and Confocal Microscopy, Methods in Molecular Biology (pp. 205-217). Springer New York
Conference proceedings papers
- Sub-cellular Heterogeneity in SERCA Determines Spatial Calcium Dynamics in Cardiomyocytes. BIOPHYSICAL JOURNAL, Vol. 118(3) (pp 172A-173A)
- Optical Superresolution Analysis of Intracellular Calcium Handling Proteins and Correlating Calcium Signal Morphology. BIOPHYSICAL JOURNAL, Vol. 118(3) (pp 172A-172A)
- 4D spatial-spectral super-resolution imaging of nanoscopic membrane signalling domains. 2011 International Quantum Electronics Conference (IQEC) and Conference on Lasers and Electro-Optics (CLEO) Pacific Rim incorporating the Australasian Conference on Optics, Lasers and Spectroscopy and the Australian Conference on Optical Fibre Technology, 28 August 2011 - 1 September 2011.
- Professional activities
- Research fellowships coordinator for MBB
- Member of advisory board for Cell Reports Physical Sciences journal
- Panel reviewer for Advance HE (Athena SWAN)