Dr Izzy Jayasinghe
School of Biosciences
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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
Medical and optical biotechnologies:
I am interested in developing novel optical analytical tools to enable better histopathological diagnostics, multi-scale imaging, and in situ omics. One of the key areas of active, ongoing work is the development of super-resolution microscopy techniques for medical and biological investigations, for visualising sub-cellular structures such as protein clusters, organelles, and disease markers.
Areas of expertise in my team include methods and protocols known as
- Expansion Microscopy
- Nanodiamond STORM
Ongoing projects include novel experimental pipelines for Expansion Microscopy which allow us to physically inflate the cells and tissues in order to resolve the finer sub-structures within them.
We are also interested in developing novel imaging probes such as nondescript fluorescent labels and photoluminescent nanodiamonds. We use advanced manufacturing methods such as 3D printing, custom optics, optical 3D modelling and novel camera technologies to develop new microscopes and microscopy protocols that are accessible, versatile, and tailored to various medical and bioimaging applications.
Biophysics of Cell Signalling:
Rapid mobilization of ions or small molecules inside cells form some of the rapid signalling mechanisms fundamental to life processes such as the heartbeat, muscle contraction, neurotransmitter release, activation of gene transcription and downstream switches such as modification of proteins and other biomolecules. The biophysics governing these mechanisms are fundamental to disease conditions such as heart disease, cancer, chronic pain, and other neurological conditions.
In my team, we leverage the novel medical and biomedical imaging methods to accurately map, visualise and track these signals and the molecules that trigger these signals in cells. In particular, we use super-resolution microscopy to visualise individual ion channels as well as individual chemical signatures throughout cells, tissues, whole organs and organisms at a resolution that matches certain versions of electron microscopy. We use these super-resolution images to construct geometrically realistic cells and protein distributions to then simulate both healthy and disease patterns of such intracellular signals.
We also hold expertise in correlative imaging protocols that allow the overlay of functional images with super-resolution structural images. These methods go towards forming some of the fundamental lines of evidence that link structural abnormalities observed in cells and tissues to the functions that manifest in human and animal disease.
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- Expansion microscopy reveals subdomains in C. elegans germ granules. Life Science Alliance, 6(4).
- Dismantling barriers faced by women in STEM. Nature Chemistry, 14(11), 1203-1206.
- 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
- Diverse labelling of cellular compartments with NHS esters in expansion microscopy. Biophysical Journal, Vol. 122(3) (pp 275a-275a)
- Correlative super-resolution microscopy of intracellular calcium release channels and fast, cytoplasmic calcium signals. ACTA PHYSIOLOGICA, Vol. 236 (pp 27-27)
- 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.
- Differential labelling of human sub-cellular compartments with fluorescent dye esters and expansion microscopy, Cold Spring Harbor Laboratory.
- Geometry-preserving Expansion Microscopy microplates enable high fidelity nanoscale distortion mapping, Cold Spring Harbor Laboratory.
- Correlative super-resolution analysis of cardiac calcium sparks and their molecular origins in health and disease, Cold Spring Harbor Laboratory.
- Cysteine post-translational modifications regulate protein interactions of caveolin-3, Cold Spring Harbor Laboratory.
- A super-resolution protocol to correlate structural underpinnings of fast second-messenger signalling in primary cell types, Cold Spring Harbor Laboratory.
- Expansion microscopy reveals subdomains in C. elegans germ granules, Cold Spring Harbor Laboratory.
- Professional activities and memberships
- Deputy School Director for Research & Innovation (2022 -)
- Deputy lead of Division of Molecular & Cellular Biology (2021 -)
- Member of the Strategic Advisory Team for EPSRC (Physical Sciences; 2021-2024)
- Editorial board member for Journal of Microscopy (2022-2026)
- Member of advisory board for Cell Reports Physical Sciences journal (2020 -)
- Panel reviewer for Advance HE (Athena SWAN; 2018-)