Faculty of Biological Sciences

Dr Isuru Jayasinghe

Lecturer in Cardiovascular Science
School of Biomedical Sciences

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, email address for  

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. 


You can follow a more up-to-date feed of my research interests and development on Twitter 

 

 

Current Projects

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 

 

Faculty Research and Innovation

Modules taught

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)

Providing laboratory research support for multiple PIs, training new staff and laboratory/office management 

Postgraduates

Miriam Hurley (Primary supervisor) 50% FTE
Thomas Sheard (Primary supervisor) 34% FTE
Lucia Pedicini (Co-supervisor) 10% FTE

Lin R, Clowsley AH, Jayasinghe ID, Baddeley D, Soeller C Algorithmic corrections for localization microscopy with sCMOS cameras - characterisation of a computationally efficient localization approach Optics Express 25 11701-11716, 2017
DOI:10.1364/OE.25.011701
View abstract

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
DOI:10.1038/ncomms14266
View abstract

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
DOI:10.1136/heartjnl-2016-310696.7

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
DOI:10.1242/jcs.196873
View abstract

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
DOI:10.1016/j.ymeth.2015.03.011
View abstract

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
DOI:10.1016/j.yjmcc.2014.12.013
View abstract

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
DOI:10.4081/ejtm.2015.4747
View abstract

Jayasinghe ID, Munro M, Baddeley D, Launikonis BS, Soeller C 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 -, 2014
DOI:10.1098/rsif.2014.0570
View abstract

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
DOI:10.1016/j.pbiomolbio.2014.07.003
View abstract

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
DOI:10.1242/jcs.131565
View abstract

Jayasinghe I, Launikonis BS Three-dimensional reconstruction and analysis of the tubular system of vertebrate skeletal muscle J Cell Sci -, 2013
DOI:10.1242/​jcs.131565
View abstract

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
DOI:10.1016/j.bpj.2013.04.029.
View abstract

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 -, 2013
DOI:10.1016/j.bpj.2013.04.029
View abstract

Jayasinghe ID, Crossman DJ, Soeller C, Cannell MB Comparison of the organization of t-tubules, sarcoplasmic reticulum and ryanodine receptors in rat and human ventricular myocardium Clinical and Experimental Pharmacology and Physiology 39 469-476, 2012
DOI:10.1111/j.1440-1681.2011.05578.x
View abstract

Jayasinghe ID, Baddeley D, Kong CHT, Wehrens XHT, Cannell MB, Soeller C Nanoscale organization of junctophilin-2 and ryanodine receptors within peripheral couplings of rat ventricular cardiomyocytes Biophysical Journal 102 -, 2012
DOI:10.1016/j.bpj.2012.01.034
View abstract

Baddeley D, Jayasinghe I, Kong C, Crossman D, Cheyne J, Montgomery J, Cannell M, Soeller C 4D spatial-spectral super-resolution imaging of nanoscopic membrane signalling domains, 2011
View abstract

Baddeley D, Jayasinghe I, Kong C, Crossman D, Cheyne J, Montgomery J, Cannell M, Soeller C 4D spatial-spectral super-resolution imaging of nanoscopic membrane signalling domains, 2011
DOI:10.1109/IQEC-CLEO.2011.6194007
View abstract

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 -, 2011
DOI:10.1371/journal.pone.0020645
View abstract

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
DOI:10.1016/j.yjmcc.2009.12.012
View abstract

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
DOI:10.1073/pnas.0908971106
View abstract

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
DOI:10.1016/j.bpj.2009.08.036
View abstract

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
DOI:10.1113/expphysiol.2008.043976
View abstract

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 -, 2009
DOI:10.1016/j.bpj.2008.11.002
View abstract

Crossman DJ, Jayasinghe ID, Soeller C Transverse tubule remodelling: a cellular pathology driven by both sides of the plasmalemma? Biophysical Reviews -,
DOI:10.1007/s12551-017-0273-7
View abstract