Dr Izzy Jayasinghe

School of Biosciences

Senior Lecturer

i.jayasinghe@sheffield.ac.uk

Firth Court

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Dr Izzy Jayasinghe
School of Biosciences
Firth Court
Western Bank
Sheffield
S10 2TN

Profile

Career History

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

Cell Signalling

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.

Super-resolution microscopy

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).

Publications

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Journal articles

Bristow RG, Engel J, Jayasinghe I, Kampmann M, James Sansom O & Bryant DM (2022) Conversations with LGBT+ scientists about visibility, leadership and climbing the career ladder. Journal of Cell Science, 135(4).
Armada-Moreira A, Cizauskas C, Fleury G, Forslund SK, Guthman EM, Hanafiah A, Hope JM, Jayasinghe I, McSweeney D & Young ID (2021) STEM Pride: Perspectives from transgender, nonbinary, and genderqueer scientists. Cell, 184(13), 3352-3355.
Hurley ME, Sheard TMD, Norman R, Kirton HM, Shah SS, Pervolaraki E, Yang Z, Gamper N, White E, Steele D & Jayasinghe I (2020) A correlative super-resolution protocol to visualise structural underpinnings of fast second-messenger signalling in primary cell types. Methods.
Colman MA, Holmes M, Whittaker DG, Jayasinghe I & Benson AP (2020) 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
Miteva KT, Pedicini L, Wilson LA, Jayasinghe I, Slip RG, Marszalek K, Gaunt HJ, Bartoli F, Deivasigamani S, Sobradillo D , Beech DJ et al (2019) 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
Sheard TMD, Hurley ME, Colyer J, White E, Norman R, Pervolaraki E, Narayanasamy KK, Hou Y, Kirton HM, Yang Z , Hunter L et al (2019) 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
Jayasinghe I, Clowsley AH, de Langen O, Sali SS, Crossman DJ & Soeller C (2018) Shining new light on the structural determinants of cardiac couplon function : insights from ten years of nanoscale microscopy. Frontiers in Physiology, 9.
Jayasinghe I, Clowsley AH, Lin R, Lutz T, Harrison C, Green E, Baddeley D, Di Michele L & Soeller C (2018) True molecular scale visualization of variable clustering properties of ryanodine receptors. Cell Reports, 22(2), 557-567. View this article in WRRO
Crossman DJ, Jayasinghe ID & Soeller C (2017) Transverse tubule remodelling: a cellular pathology driven by both sides of the plasmalemma?. Biophysical Reviews, 9(6), 919-929. View this article in WRRO
Lin R, Clowsley AH, Jayasinghe ID, Baddeley D & Soeller C (2017) 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
Cully TR, Murphy RM, Roberts L, Raastad T, Fassett RG, Coombes JS, Jayasinghe ID & Launikonis BS (2017) 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
Munro ML, Jayasinghe ID, Wang Q, Quick A, Wang W, Baddeley D, Wehrens XHT & Soeller C (2016) 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
Crossman DJ, Hou Y, Jayasinghe I, Baddeley D & Soeller C (2015) Combining confocal and single molecule localisation microscopy: A correlative approach to multi-scale tissue imaging. Methods, 88, 98-108.
Hou Y, Jayasinghe I, Crossman DJ, Baddeley D & Soeller C (2015) Nanoscale analysis of ryanodine receptor clusters in dyadic couplings of rat cardiac myocytes. Journal of Molecular and Cellular Cardiology, 80, 45-55.
Jayasinghe ID, Munro M, Baddeley D, Launikonis BS & Soeller C (2014) 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.
Hou Y, Crossman DJ, Rajagopal V, Baddeley D, Jayasinghe I & Soeller C (2014) 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.
Jayasinghe ID & Launikonis BS (2013) Three-dimensional reconstruction and analysis of the tubular system of vertebrate skeletal muscle. Journal of Cell Science, 126(17), 4048-4058.
Jayasinghe ID, Lo HP, Morgan GP, Baddeley D, Parton RG, Soeller C & Launikonis BS (2013) Examination of the Subsarcolemmal Tubular System of Mammalian Skeletal Muscle Fibers. Biophysical Journal, 104(11), L19-L21.
Jayasinghe ID, Crossman DJ, Soeller C & Cannell MB (2012) 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.
Jayasinghe ID, Baddeley D, Kong CHT, Wehrens XHT, Cannell MB & Soeller C (2012) Nanoscale Organization of Junctophilin-2 and Ryanodine Receptors within Peripheral Couplings of Rat Ventricular Cardiomyocytes. Biophysical Journal, 102(5), L19-L21.
Jayasinghe ID, Crossman DJ, Soeller C & Cannell MB (2010) 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.
Baddeley D, Jayasinghe ID, Lam L, Rossberger S, Cannell MB & Soeller C (2009) 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.
Jayasinghe ID, Cannell MB & Soeller C (2009) Organization of Ryanodine Receptors, Transverse Tubules, and Sodium-Calcium Exchanger in Rat Myocytes. Biophysical Journal, 97(10), 2664-2673.
Soeller C, Jayasinghe ID, Li P, Holden AV & Cannell MB (2009) 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.
Baddeley D, Jayasinghe ID, Cremer C, Cannell MB & Soeller C (2009) Light-Induced Dark States of Organic Fluochromes Enable 30 nm Resolution Imaging in Standard Media. Biophysical Journal, 96(2), L22-L24.
Sheard T, Hurley M, Smith A, Colyer J, White E & Jayasinghe I () 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.
Holmes M, Sheard T, Hurley M, Benson A, Jayasinghe I & Colman M () 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.
Sheard TMD, Hurley ME, Smith AJ, Colyer J, White E & Jayasinghe I () Molecular-scale 3D visualisation of the cardiac ryanodine receptor clusters and the molecular-scale fraying of dyads.
Jayasinghe ID, Clowsley AH, Munro M, Hou Y, Crossman DJ & Soeller C () Revealing t-tubules in striated muscle with new optical super-resolution microscopy techniques. European Journal of Translational Myology, 25(1), 15-15.
Narayanasamy KK, Price JC, Mesquita-Riberio R, Mather ML & Jayasinghe I () Self-activated photoblinking of nitrogen vacancy centers in nanodiamonds (sandSTORM): A method for rapid single molecule localization microscopy with unlimited observation time.
Baddeley D, Crossman D, Rossberger S, Cheyne JE, Montgomery JM, Jayasinghe ID, Cremer C, Cannell MB & Soeller C () 4D Super-Resolution Microscopy with Conventional Fluorophores and Single Wavelength Excitation in Optically Thick Cells and Tissues. PLoS ONE, 6(5), e20645-e20645.
Sheard TMD, Howlett L, Kirton H, Yang Z, Gurrola G, Steele D, Jayasinghe I, Valdivia HH & Colyer J () Peptide ligands of the cardiac ryanodine receptor as super-resolution imaging probes.

Chapters

Sheard TMD & Jayasinghe I (2021) Enhanced expansion microscopy to measure nanoscale structural and biochemical remodeling in single cells, Methods in Cell Biology (pp. 147-180). Elsevier
Soeller C & Jayasinghe ID (2018) Quantitative Super-Resolution Microscopy of Cardiomyocytes, Microscopy of the Heart (pp. 37-73).
Jayasinghe I, Clowsley AH & Soeller C (2018) 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
Soeller C, Hou Y, Jayasinghe ID, Baddeley D & Crossman D (2017) Correlative Single-Molecule Localization Microscopy and Confocal Microscopy, Methods in Molecular Biology (pp. 205-217). Springer New York

Conference proceedings papers

Holmes M, Hurley ME, Sheard TMD, Stevenson-Cocks HJ, Benson A, Jayasinghe I & Colman MA (2020) Sub-cellular Heterogeneity in SERCA Determines Spatial Calcium Dynamics in Cardiomyocytes. BIOPHYSICAL JOURNAL, Vol. 118(3) (pp 172A-173A)
Hurley ME, Sheard TM, Norman R, Kirton HM, Shah SS, Pervolaraki E, Yang Z, Steele DS, Gamper N, White E & Jayasinghe I (2020) Optical Superresolution Analysis of Intracellular Calcium Handling Proteins and Correlating Calcium Signal Morphology. BIOPHYSICAL JOURNAL, Vol. 118(3) (pp 172A-172A)
Baddeley D, Jayasinghe I, Kong C, Crossman D, Cheyne J, Montgomery J, Cannell M & Soeller C (2011) 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)