Associate Professor Izzy Jayasinghe

Associate Professor Izzy Jayasinghe

Associate Professor

2007: Bachelor of Science  (Biomedical), First class honours, majoring in cardiovascular biology, Faculty of Science, University of Auckland, New Zealand.

2011: Doctor of Philosophy (Department of Physiology, University of Auckland, New Zealand), awarded on 04/05/2011 for the development of novel high/super-resolution imaging approaches to visualise the signalling complexes in the myocardium. The thesis was awarded the Vice Chancellor’s ‘Best Thesis’ award. Subject areas: Biophysics and biophotonics.

Medicine & Health
School of Biomedical Sciences

Associate Professor Izzy Jayasinghe was recruited to UNSW Sydney in 2023 as Head of the Department of Molecular Medicine in the School of Biomedical Sciences. Her research has and continues to be focus on developing new optical microscopy techniques for studying the organisation of the molecules of life, particularly proteins, within the heart. Izzy is a UKRI Future Leader Fellow at Sheffield University, where she is currently a Visiting Fellow and had served as Deputy Head of the Molecular and Cellular Biology Division since 2021. She built a track record in developing and applying new optical imaging methods during her postdoctoral fellowships in Queensland, and in Exeter (UK), aftre she completed a PhD in Auckland (New Zealand). In 2015, Izzy established her independent research program in the University of Leeds where she developed adaptations of optical imaging methods such as DNA-PAINT and Expansion Microscopy to study pathological nanoscale remodelling in the failing heart. Her current research focuses on developing more accessible, faster and higher resolution imaging methods for imaging optically-thick (and biologically more complex) samples. Izzy is a Fellow of the Royal Microscopical Society and advocates for Open Science and Equality and Inclusion in STEM.

Lowy Cancer Research Centre, UNSW Sydney, Kensington Campus, Sydney 2052.
  • Book Chapters | 2021
    Sheard TMD; Jayasinghe I, 2021, 'Enhanced expansion microscopy to measure nanoscale structural and biochemical remodeling in single cells', in Methods in Cell Biology, pp. 147 - 180,
    Book Chapters | 2018
    Soeller C; Jayasinghe ID, 2018, 'Quantitative Super-Resolution Microscopy of Cardiomyocytes', in Microscopy of the Heart, pp. 37 - 73
    Book Chapters | 2017
    Soeller C; Hou Y; Jayasinghe ID; Baddeley D; Crossman D, 2017, 'Correlative single-molecule localization microscopy and confocal microscopy', in Methods in Molecular Biology, pp. 205 - 217,
  • Journal articles | 2024
    Aghi K; Anderson BM; Castellano BM; Cunningham A; Delano M; Dickinson ES; von Diezmann L; Forslund-Startceva SK; Grijseels DM; Groh SS; Guthman EM; Jayasinghe I; Johnston J; Long S; McLaughlin JF; McLaughlin M; Miyagi M; Rajaraman B; Sancheznieto F; Scheim AI; Sun SD; Titmuss FD; Walsh RJ; Weinberg ZY, 2024, 'Rigorous science demands support of transgender scientists', Cell, 187, pp. 1327 - 1334,
    Journal articles | 2024
    Ashford F; Kuo CW; Dunning E; Brown E; Calagan S; Jayasinghe I; Henderson C; Fuller W; Wypijewski K, 2024, 'Cysteine post-translational modifications regulate protein interactions of caveolin-3', FASEB Journal, 38,
    Journal articles | 2024
    Hurley ME; Shah SS; Sheard TMD; Kirton HM; Steele DS; Gamper N; Jayasinghe I, 2024, 'Super-Resolution Analysis of the Origins of the Elementary Events of ER Calcium Release in Dorsal Root Ganglion Neurons', Cells, 13,
    Journal articles | 2024
    Suen KM; Sheard TM; Lin CC; Milonaityte D; Jayasinghe I; Ladbury JE, 2024, 'Erratum: Correction: Expansion microscopy reveals subdomains in C. elegans germ granules (Life science alliance (2023) 6 4 PII: e202302405)', Life science alliance, 7,
    Journal articles | 2023
    Hurley ME; White E; Sheard TMD; Steele D; Jayasinghe I, 2023, 'Correlative super-resolution analysis of cardiac calcium sparks and their molecular origins in health and disease', Open Biology, 13,
    Journal articles | 2023
    Seehra RS; Warrington SJ; Allouis BHK; Sheard TMD; Spencer ME; Shakespeare T; Cadby A; Bose D; Strutt D; Jayasinghe I, 2023, 'Geometry-preserving expansion microscopy microplates enable high-fidelity nanoscale distortion mapping', Cell Reports Physical Science, 4,
    Journal articles | 2023
    Sheard TMD; Shakespeare TB; Seehra RS; Spencer ME; Suen KM; Jayasinghe I, 2023, 'Differential labelling of human sub-cellular compartments with fluorescent dye esters and expansion microscopy', Nanoscale, 15, pp. 18489 - 18499,
    Journal articles | 2023
    Suen KM; Sheard TMD; Lin CC; Milonaityte D; Jayasinghe I; Ladbury JE, 2023, 'Expansion microscopy reveals subdomains in C. elegans germ granules', Life Science Alliance, 6,
    Journal articles | 2022
    Bristow RG; Engel J; Jayasinghe I; Kampmann M; Sansom OJ; Bryant DM, 2022, 'Conversations with LGBT+ scientists about visibility, leadership and climbing the career ladder', Journal of Cell Science, 135,
    Journal articles | 2022
    Colman MA; Alvarez-Lacalle E; Echebarria B; Sato D; Sutanto H; Heijman J, 2022, 'Multi-Scale Computational Modeling of Spatial Calcium Handling From Nanodomain to Whole-Heart: Overview and Perspectives.', Front Physiol, 13, pp. 836622,
    Journal articles | 2022
    Holmes M; Hurley ME; Sheard TMD; Benson AP; Jayasinghe I; Colman MA, 2022, 'Increased SERCA2a sub-cellular heterogeneity in right-ventricular heart failure inhibits excitation-contraction coupling and modulates arrhythmogenic dynamics', Philosophical Transactions of the Royal Society B: Biological Sciences, 377,
    Journal articles | 2022
    Jebsen JM; Nicoll Baines K; Oliver RA; Jayasinghe I, 2022, 'Dismantling barriers faced by women in STEM', Nature Chemistry, 14, pp. 1203 - 1206,
    Journal articles | 2022
    Sheard TMD; Hurley ME; Smith AJ; Colyer J; White E; Jayasinghe I, 2022, 'Three-dimensional visualization of the cardiac ryanodine receptor clusters and the molecular-scale fraying of dyads', Philosophical Transactions of the Royal Society B: Biological Sciences, 377,
    Journal articles | 2021
    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, pp. 3352 - 3355,
    Journal articles | 2021
    Colman MA; Holmes M; Whittaker DG; Jayasinghe I; Benson AP, 2021, 'Multi-scale approaches for the simulation of cardiac electrophysiology: I – Sub-cellular and stochastic calcium dynamics from cell to organ', Methods, 185, pp. 49 - 59,
    Journal articles | 2021
    Hurley ME; Sheard TMD; Norman R; Kirton HM; Shah SS; Pervolaraki E; Yang Z; Gamper N; White E; Steele D; Jayasinghe I, 2021, 'A correlative super-resolution protocol to visualise structural underpinnings of fast second-messenger signalling in primary cell types', Methods, 193, pp. 27 - 37,
    Journal articles | 2020
    Jebsen JM; Abbott C; Oliver R; Ochu E; Jayasinghe I; Gauchotte-Lindsay C, 2020, 'Review of barriers women face in research funding processes in the UK', Psychology of Women and Equalities Section Review, 3, pp. 3 - 14,
    Journal articles | 2019
    Miteva KT; Pedicini L; Wilson LA; Jayasinghe I; Slip RG; Marszalek K; Gaunt HJ; Bartoli F; Deivasigamani S; Sobradillo D; Beech DJ; McKeown L, 2019, 'Rab46 integrates Ca2+ and histamine signaling to regulate selective cargo release from Weibel-Palade bodies', Journal of Cell Biology, 218, pp. 2232 - 2246,
    Journal articles | 2019
    Sheard TMD; Hurley ME; Colyer J; White E; Norman R; Pervolaraki E; Narayanasamy KK; Hou Y; Kirton HM; Yang Z; Hunter L; Shim JU; Clowsley AH; Smith AJ; Baddeley D; Soeller C; Colman MA; Jayasinghe I, 2019, 'Three-dimensional and chemical mapping of intracellular signaling nanodomains in health and disease with enhanced expansion microscopy', ACS Nano, 13, pp. 2143 - 2157,
    Journal articles | 2018
    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,
    Journal articles | 2018
    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, pp. 557 - 567,
    Journal articles | 2018
    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, 28, pp. 167 - 197,
    Journal articles | 2017
    Crossman DJ; Jayasinghe ID; Soeller C, 2017, 'Transverse tubule remodelling: a cellular pathology driven by both sides of the plasmalemma?', Biophysical Reviews, 9, pp. 919 - 929,
    Journal articles | 2017
    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,
    Journal articles | 2017
    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, pp. 11701 - 11716,
    Journal articles | 2016
    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, pp. 4388 - 4398,
    Journal articles | 2015
    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, pp. 98 - 108,
    Journal articles | 2015
    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, pp. 45 - 55,
    Journal articles | 2015
    Jayasinghe ID; Clowsley AH; Munro M; Hou Y; Crossman DJ; Soeller C, 2015, 'Revealing T-Tubules in Striated Muscle with New Optical Super-Resolution Microscopy Techniquess.', Eur J Transl Myol, 25, pp. 4747,
    Journal articles | 2014
    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, pp. 328 - 339,
    Journal articles | 2014
    Jayasinghe ID; Munro M; Baddeley D; Launikonis BS; Soeller C, 2014, 'Observation of the molecular organization of calcium release sites in fast- and slowtwitch skeletal muscle with nanoscale imaging', Journal of the Royal Society Interface, 11,
    Journal articles | 2013
    Jayasinghe I; 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,
    Journal articles | 2013
    Jayasinghe ID; Launikonis BS, 2013, 'Three-dimensional reconstruction and analysis of the tubular system of vertebrate skeletal muscle', Journal of Cell Science, 126, pp. 4048 - 4058,
    Journal articles | 2012
    Jayasinghe I; 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,
    Journal articles | 2012
    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, pp. 469 - 476,
    Journal articles | 2011
    Baddeley D; Crossman D; Rossberger S; Cheyne JE; Montgomery JM; Jayasinghe ID; Cremer C; Cannell MB; Soeller C, 2011, '4D super-resolution microscopy with conventional fluorophores and single wavelength excitation in optically thick cells and tissues', PLoS ONE, 6,
    Journal articles | 2010
    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, pp. 964 - 971,
    Journal articles | 2009
    Baddeley D; Jayasinghe I; 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,
    Journal articles | 2009
    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 of the United States of America, 106, pp. 22275 - 22280,
    Journal articles | 2009
    Jayasinghe I; Cannell MB; Soeller C, 2009, 'Organization of ryanodine receptors, transverse tubules, and sodium-calcium exchanger in rat myocytes', Biophysical Journal, 97, pp. 2664 - 2673,
    Journal articles | 2009
    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, pp. 496 - 508,
  • Preprints | 2023
    Hurley M; White E; Sheard TMD; Steele D; Jayasinghe I, 2023, Correlative super-resolution analysis of cardiac calcium sparks and their molecular origins in health and disease, ,
    Preprints | 2023
    Seehra R; Allouis BHK; Sheard TMD; Spencer M; Shakespeare T; Cadby A; Jayasinghe I, 2023, Geometry-preserving Expansion Microscopy microplates enable high fidelity nanoscale distortion mapping, ,
    Preprints | 2023
    Sheard T; Shakespeare T; Seehra R; Spencer M; Suen K; Jayasinghe I, 2023, Differential labelling of human sub-cellular compartments with fluorescent dye esters and expansion microscopy, ,
    Preprints | 2022
    Ashford F; Brown E; Calagan S; Jayasinghe I; Henderson C; Fuller W; Wypijewski K, 2022, Cysteine post-translational modifications regulate protein interactions of caveolin-3, ,
    Preprints | 2022
    Suen K; Sheard T; Lin C-C; Milonaityte D; Jayasinghe I; Ladbury J, 2022, Expansion microscopy reveals subdomains in C. elegans germ granules, ,
    Preprints | 2021
    Sheard T; Hurley M; Smith A; Colyer J; White E; Jayasinghe I, 2021, Molecular-scale 3D visualisation of the cardiac ryanodine receptor clusters and the molecular-scale fraying of dyads, ,
    Preprints | 2020
    Narayanasamy K; Price J; Mesquita-Riberio R; Mather M; Jayasinghe I, 2020, Self-activated photoblinking of nitrogen vacancy centers in nanodiamonds (sandSTORM): A method for rapid single molecule localization microscopy with unlimited observation time, ,
    Preprints | 2020
    Sheard T; Howlett L; Kirton H; Yang Z; Gurrola G; Steele D; Jayasinghe I; Valdivia H; Colyer J, 2020, Peptide ligands of the cardiac ryanodine receptor as super-resolution imaging probes, ,
    Conference Papers | 2011
    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', in 2011 Int. Quantum Electron. Conf., IQEC 2011 and Conf. Lasers and Electro-Optics, CLEO Pacific Rim 2011 Incorporating the Australasian Conf. Optics, Lasers and Spectroscopy and the Australian Conf., pp. 77 - 78,
    Conference Papers | 2011
    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', in Optics InfoBase Conference Papers, pp. 77 - 78

2024       New South Wales Health Elite Cardiovascular Researcher Award, “Visualising the spatial heterogeneity in heart failure”, $1m (AUD). Chief Investigator: Jayasinghe. Start 1 Mar 2024. Duration 36 months.

2022*      Medical Research Council (UK), Capital Award. “An Airyscan 2 confocal microscope for the Wolfson Light Microscopy Facility”. MR/X012077/1. fEC: £980k. PI: Smythe, E. Co-I: Jayasinghe, Strutt, Whitfield,

2021*      Biotechnology and Biological Sciences Research Council (BBSRC) Responsive Mode grant “Divide and rule: localised Ca2+ signalling in sensory neurons” BB/V010344/1. Duration 3 years (June 2021-May2024) fEC £568k PI: Nikita Gamper, Co-I (Sheffield PI): I. Jayasinghe

2021*      Engineering & Physical Sciences Council (EPSRC) PhD studentship, “Developing a novel histopathology toolkit”, Duration: 42 months. Value: £146k (stipend & research expenses). PI: Jayasinghe, Co-I: Cadby

2019*      UK Research and Innovation Future Leader Fellowship. “Taking super resolution microscopy beyond the laboratory” MR/S03241X/1. Duration 7-years (May 2020-April 2027). fEC for first 4 years £1.13m. PI: Jayasinghe.

2020       Australian Research Council Discovery project. “Sarcoplasmic reticulum-mitochondrial functional interactions in muscle”. DP200100435. Chief Investigator: Launikonis; Partner Investigator Jayasinghe, Soeller. Duration: 36 months; Value: $512k (AUD)

2019       Integrated Biological Imaging Network pump-priming project grant. “High-speed 3D Fluorescence Lifetime Imaging of Force in Cardiomyocytes” Duration 6-months (Sep 2019- Feb2020). fEC £28k). PI: Simon Ameer-Beg; Co-I: Caroline Müllenbroich, Izzy Jayasinghe.

2019       BBSRC 18alert Mid-range Equipment initiative. BB/S019464/1 “Stimulated Emission Depletion Microscopy (STED) for imaging at high resolution in the Biosciences” (£719k) Principal Investigator: Peckham, Co-Is: Jayasinghe, Beech, Stonehouse, Ponnambalam, Johnson

2018       British Heart Foundation project grant “Cavins - mobile regulators of adrenoceptor signalling” (£128k; 24 months) PI: Calaghan, Co-I: Jayasinghe, White, Colyer

2017       Wellcome Trust Seed Award “Harnessing the molecular-scale resolution of DNA-PAINT to study the structural basis of electrical signals of the healthy and arrhythmic hearts” 207684/Z/17/Z (£100k; 24 months;). PI: Jayasinghe

2017       British Heart Foundation project grant “The role of Ca2+ signalling in the regulation of Weibel Palade Body trafficking” (£161k; 36 months;). PI: McKeown, Co-I: Jayasinghe, Beech

2016       MRC 4-year doctoral studentship from competition funding for project titled “Shining light on the molecular scale remodelling in a heart’s path to failure” (£146k; 4 years; commencing in Oct 2016). PI: Jayasinghe, Co-Is: Andrew Smith, John Colyer

2015       British Heart Foundation grant “Cavins: mobile regulators of β-adrenoceptor signalling in the cardiac cell” (£227k; 3 years; £10k in research funds and a postdoc for Jayasinghe for 12 months). PI: Fuller, Co-I: Calaghan, Jayasinghe

2015       Wellcome Trust ISSF 3-year Early Career Fellowship. “Novel optical tools for probing structural basis of cellular physiology”. Salary + £60k consumables. Forfeited to take up Lectureship in University of Leeds.

2023       “40 under 40” award as an Innovator and Disruptor, awarded to alumni of the University of Auckland.

2022       Fellow of the Royal Microscopical Society, UK.

2021       Fellow (Foundation Future Leader) of the Foundation for Science & Technology, London, UK

2020       Finalist at the UK National Diversity Awards as “Positive Role Model”

2019       Departmental nominee towards the Blavatnik Award for Young Scientists in Life Sciences

2019       ‘New & Notable’ award & plenary lecture at the 27th Northern Cardiovascular Research Group meeting, UK

2012       University of Queensland New Staff Start-up competition award (AU $12k)

2011       University of Auckland Vice Chancellor’s prize for the ‘Best Doctoral Thesis’ of 2010 (NZ $6k)

2010       Hubbard memorial prize for 2010 awarded by the Physiological Society of New Zealand for excellence in studies towards a PhD in Physiology

2010       Early thesis submission award for doctoral studies at the University of Auckland (NZ $6k)

2008       Winner of the annual scientific image competition organised by the Biomedical Imaging Research Unit in the University of Auckland

2007       Senior scholarship for 36 months from the Auckland Medical Research Foundation -AMRF- (NZ $97k)

2007       Health Research Doctoral scholarship for 42 months from the University of Auckland (NZ $87.5k)

2007       Lottery Health research PhD scholarship for 36 months (NZ $72k; forfeited to accept AMRF offer)

2007       Prime Minister’s Top Achiever doctoral scholarship for 36 months from the Tertiary Education Commission (NZ $96k; forfeited to accept AMRF offer)

2007       Student presentation prize at the Australian Physiological Society congress held in Newcastle, Australia.

2005       Senior prize in Physiology for undergraduate studies in the Department of Physiology, University of Auckland (NZ $50)

2002       Winner in Senior Physics and of the Junior Scientist award of the Faculty of Science (University of Auckland) at the 2002 NIWA Auckland Science Fair (NZ $1,000)

Electrical and chemical signals generated within cells, tissues and organ systems drive vital functions. Izzy Jayasinghe and her team investigate how these signals are relayed to trigger a heartbeat, and drive other bodily functions, by combing super-resolution microscopy tools they develop with existing technologies.

Most cells contain specialised hubs of signalling proteins and accessory molecules that propagate fast, large, and repeatable signals pivotal to healthy heart rhythm and other critical functions. Now that we know these hubs are wired differently in heart failure, chronic pain, and muscle weakness, Izzy’s team - the Signalling Nanodomains Laboratory - build biochemical maps of these signals to unravel disease processes, and to design and refine novel precision therapeutics.

Cell signalling and disease

Rapid mobilization of ions or small molecules inside cells are amongst some of the fastest signalling mechanisms fundamental to life. They underpin physiologies such as the heartbeat, muscle contraction, neurotransmitter release, activation of gene transcription, and post-translational modifications. These mechanisms are also responsible for major human diseases and disabilities such as heart disease, cancer, paralysis, and chronic pain. Many such morbidities have no cure, whilst effectiveness of pharmacological treatments tends to be variable. At the core of some of the underpinning fast signals, are intracellular calcium signals (calcium sparks, puffs, waves, or transients) in excitable cells like muscle and neural tissues. They consist of specialised, nanoscale signalling domains that harbour ion channels and accessory molecules that coordinate to generate calcium sparks.

For over 15 years, our group have harnessed the power of a range of super-resolution microscopy technologies to resolve and visualise the shapes, locations, and molecular components intrinsic to these nanodomains (Jayasinghe et al, 2018). We now have the microscopy and analysis tools to not only map the position of each ion channel within these domains, but also to detect specific biochemical signatures on each channel, in situ (Sheard et al, 2019). For decades, the nanodomains and their signals have been imaged in isolation. However, one of our recent innovations, a correlative microscopy protocol (Hurley et al, 2021Hurley et al, 2023), has allowed us to visualise the communications of channels such as ryanodine receptors can produce unexpected patterns of calcium signals. In particular, our discoveries have unearthed spatial heterogeneities in the organisation of calcium handling proteins of the myocardium. Our early observations suggest that these heterogeneities are not limited calcium handling proteins (such as ryanodine receptors (RyR2), L-type calcium channels, SERCA2A, and sodium calcium exchanger) but extend to regulatory molecules, second messengers, nucleic acids, and other structural proteins across the multitude of cells in the healthy heart. We also observe that these variabilities are accentuated in heart disease and may explain the limited effectiveness of the past and present generations of pharmacological therapies targeting the myocardial contractility.

Democratising super-resolution and high resolution optical imaging

Super-resolution microscopy, since its inception over two decades ago, has unlocked numerous secrets of the life processes. We have been one of the earliest adopters of this technology in its wide-ranging incarnations known commonly by numerous acronyms such as STORM, PALM, PAINT, STED and SIM. In spite of the nanometre-scale resolution that is on offer, access and usability of these methods remain modest due to the specialist nature of both the probes and the microscopy instrumentation. Over the past few years, our team have developed expertise in expansion microscopy (ExM) which parallels, and often exceeds, the resolution afforded through the traditional, localization- or optics-based super-resolution techniques. ExM uses molecular crosslinking and tissue clearing chemistries to obtain a three-dimensional imprint of cells, tissues, and/or whole organisms onto a polyacrylamide hydrogel (Sheard et al. 2019). These gels can then be osmotically swollen by a factor of >1000, effectively magnifying the intricate details of the sample that were previously too small to be resolved. ExM samples therefore allow us to visualise nanoscale features of cells and tissues conveniently with standard, and sometimes homebuilt, microscopes. Alongside of this methodology, we have been developing a series of tools that include high-throughput arrays, a new palette of fluorescent counterstains, distortion detection tools, gel automation robotics and 3D printable microscopy platforms to allow non-specialist microscopists to adopt super-resolution.

  • Featured in UNSW press brief, "UNSW researcher awarded NSW Health cardiovascular grant"
  • Scientist to Watch feature in The Scientist magazine, "Izzy Jayasinghe Harnesses Cutting-Edge Microscopy to Image Cells"
  • Featured in eLife interview, "Equity, Diversity and Inclusion: TIGER in STEMM"
  • Scientific organizer of the Royal Microscopical Society’s bi-annual super-resolution workshop, July 2023.
  • Parliamentary witness, at the Diversity & Inclusion in STEM inquiry at the Science & Technology Select Committee, UK House of Commons (April 2022) – watch recording here.
  • Co-organiser of the Inaugural TIGERinSTEMM webinar series in physics, showcasing the research of diverse members of the UK’s physics community. See “Diversity leads to impact: what we learned from running an inclusive and accessible physics webinar series” blog post in Nature Reviews Physics (2021) summarising the impact of this series.
  • Featured interview (at 50:00 min) on BBC Radio4 Today programme’s 2023 New Year’s Eve edition on ‘Opportunities in science, technology and innovation’, edited by Anne-Marie Imafidon.
  • Women in Science Week 2021 public lecture, “Understanding the gendered and intersectional inequalities in academic STEM” (Department of Chemistry, Kings College London; 11/11/2021)
  • Featured in mini-documentary on ‘Simplifying microscopy technology’, commissioned by UKRI for the UK Department of Science & Technology.
  • Contributor and signatory to the Written Evidence Submitted by The Inclusion Group for Equity in Research in STEMM (TIGERS) in the parliamentary inquiry into Diversity and Inclusion in STEM (2022) of the Science & Technology Select Committee, UK Parliament.


My Research Supervision

Tayla Shakespeare (PhD candidate)

Rajpinder Seehra (PhD candidate)

Nkolika Atuanya (PhD candidate)

Felecia Sutton (PhD candidate)