Background: I completed my basic qualifications (BSc Hons with a major in Cardiovascular Sciences and PhD in Physiology) in the University of Auckland, New Zealand. My postdoctoral trainings were in the Department of Physiology of the University of Auckland (2010-2011), School of Biomedical Sciences of the University of Queensland, Australia (2011-2013) and the College of Physics of the University of Exeter, UK (2013-2015).
Contact: Garstang 7.52a, +44(0) 113 34 39683,
My research focuses on the calcium signalling that is at the heart of the contractile function of the muscle cells of the heart. It is primarily the structural organisation of the internal structure within each cell that guarantees the forceful and synchronous contraction of each cell from beat to beat. In particular, I am interested in the signalling within and around ‘dyads’ where invaginations of the surface membrane (t-tubules) meet the internal calcium store (sarcoplasmic reticulum) to form what is essentially an ‘intracellular synapse’. Within this synapse, is the giant calcium-release channels: the ~2 MDa ryanodine receptors (RyR), organised into near-crystalline arrays. One of the key areas of interested in my lab is how the structure, organisation and post-translational modifications of proteins associated with cardiac muscle dyads determine the nature of the local calcium signal and ultimately the contractile performance of the cell. In a range of heart pathologies, this dyad structure is disrupted; t-tubules are lost or remodelled as a result of the loss or breakdown of proteins that tether these membranes together. In ongoing work, I am probing the mechanisms that are in place to maintain these structures and how they may be altered in pathology as well as non-pathological remodelling.
I study these functional aspects within cells through either live-cell calcium imaging and fluorescence detection of dynamic changes in membrane compartments. For this, I utilise microfluidic cell traps, often referred to as 'a lab on a chip', which can mimic and simulate the extracellular environment of muscle cells in the heart. Cells within these chips can be examined for various functional behaviours (e.g. calcium signalling) or structures (fluorescence imaging of membranes, organelles, protein assemblies) to understand the three-dimensional organisation of various molecular components within the cell. We achieve this through high- or super-resolution optical microscopy techniques combined with a range of image analysis tools. For example, 3D reconstructions of confocal image series are a useful approach to visualise the intracellular architecture (see video above). This type of data are also useful for interpreting calcium data or to computationally simulate the cell-wide calcium signals that activate the muscle contraction.
Super-resolution microscopy furthers this understanding by resolving the specific structures (e.g. t-tubules which are often narrower than 200 nm) or protein clusters (e.g. RyR; see image below). With single-protein-level resolution, we now routinely observe single proteins with a capacity to quantify protein-protein interactions, estimate protein expression and movements within nanometre-scale spaces within cells.
My lab currently has a number of open or upcoming vacant positions:
Advanced super-resolution microscopy approaches to observing the membrane remodelling mechanisms in the ischemic heart
Currently on offer, is a fully funded PhD scholarship to study the molecular changes underpinning the healthy and pathological cellular plasticity in heart muscle cells. The project involves the use of state-of-the-art calcium imaging and super-resolution microscopy technologies, and integration into an internationally-leading cardiac microscopy network. See further details at this link on FindAPhD.com.
Please contact Dr Jayasinghe via email or phone for further information
BMSC1213 - Basic Laboratory and Scientific Skills 2
BMSC2120 - Scientific Skills
BMSC3233/35/36 - Advanced Topics II
BMSC3301 - Research Project in Biomedical Sciences
BMSC5301M - Advanced Research Topics
Group Leader Dr Isuru Jayasinghe (Lecturer in Cardiovascular Science)
Dr Kathleen Wright (Senior Scientific Officer in Cardiovascular Science)
Supporting laboratory research development, training and management in the department of Cardiovascular Sciences
Cully TR, Murphy RM, Roberts L, Raastad T, Fassett RG, Coombes JS, Jayasinghe ID, Launikonis BS Human skeletal muscle plasmalemma alters its structure to change its Ca<sup>2+</sup>-handling following heavy-load resistance exercise Nature Communications 8 -, 2017
Jayasinghe I, Clowsley A, Lutz T, Green E, Lin R, di Michele L, Soeller C TRUE MOLECULAR SCALE ANALYSIS OF THE CALCIUM RELEASE MACHINERY OF THE HEART WITH ENHANCED SUPER-RESOLUTION IMAGING, 2016
Lin R, Clowsley A, Baddeley D, Jayasinghe I, Soeller C Single Molecule Localisation Microscopy with sCMOS Cameras, 2016
Munro ML, Jayasinghe ID, Wang Q, Quick A, Wang W, Baddeley D, Wehrens XHT, Soeller C Junctophilin-2 in the nanoscale organisation and functional signalling of ryanodine receptor clusters in cardiomyocytes Journal of Cell Science 129 4388-4398, 2016
Crossman DJ, Hou Y, Jayasinghe I, Baddeley D, Soeller C Combining confocal and single molecule localisation microscopy: A correlative approach to multi-scale tissue imaging. Methods (San Diego, Calif.) 88 98-108, 2015
Hou Y, Jayasinghe I, Crossman DJ, Baddeley D, Soeller C Nanoscale analysis of ryanodine receptor clusters in dyadic couplings of rat cardiac myocytes Journal of Molecular and Cellular Cardiology 80 45-55, 2015
Jayasinghe ID, Clowsley AH, Munro M, Hou Y, Crossman DJ, Soeller C Revealing T-Tubules in Striated Muscle with New Optical Super-Resolution Microscopy Techniquess. European journal of translational myology 25 4747-, 2015
Jayasinghe ID, Munro M, Baddeley D, Launikonis BS, Soeller C 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 -, 2014
Hou Y, Crossman DJ, Rajagopal V, Baddeley D, Jayasinghe I, Soeller C 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 115 328-339, 2014
Jayasinghe ID, Launikonis BS Three-dimensional reconstruction and analysis of the tubular system of vertebrate skeletal muscle. Journal of cell science 126 4048-4058, 2013
Jayasinghe I, Lo HP, Morgan GP, Baddeley D, Parton RG, Soeller C, Launikonis B Examination of the sub-sarcolemmal tubular system of mammalian skeletal muscle fibres Biophys J -, 2013
Jayasinghe ID, Lo HP, Morgan GP, Baddeley D, Parton RG, Soeller C, Launikonis BS Examination of the subsarcolemmal tubular system of mammalian skeletal muscle fibers. Biophysical journal 104 L19-L21, 2013
Jayasinghe I, Crossman D, Soeller C, Cannell M Comparison of the organization of T-tubules, sarcoplasmic reticulum and ryanodine receptors in rat and human ventricular myocardium. Clinical and experimental pharmacology&physiology 39 469-476, 2012
Jayasinghe ID, Baddeley D, Kong CH, Wehrens XH, Cannell MB, Soeller C Nanoscale organization of junctophilin-2 and ryanodine receptors within peripheral couplings of rat ventricular cardiomyocytes. Biophysical journal 102 L19-L21, 2012
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 e20645-, 2011
Jayasinghe ID, Crossman DJ, Soeller C, Cannell MB A new twist in cardiac muscle: dislocated and helicoid arrangements of myofibrillar z-disks in mammalian ventricular myocytes. Journal of molecular and cellular cardiology 48 964-971, 2010
Baddeley D, Jayasinghe ID, Lam L, Rossberger S, Cannell MB, Soeller C 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 22275-22280, 2009
Jayasinghe ID, Cannell MB, Soeller C Organization of ryanodine receptors, transverse tubules, and sodium-calcium exchanger in rat myocytes. Biophysical journal 97 2664-2673, 2009
Soeller C, Jayasinghe ID, Li P, Holden AV, Cannell MB Three-dimensional high-resolution imaging of cardiac proteins to construct models of intracellular Ca<sup>2+</sup>signalling in rat ventricular myocytes Experimental Physiology 94 496-508, 2009
Baddeley D, Jayasinghe ID, Cremer C, Cannell MB, Soeller C Light-induced dark states of organic fluochromes enable 30 nm resolution imaging in standard media. Biophysical journal 96 L22-L24, 2009