Dr Izzy Jayasinghe
- Position: Lecturer in Cardiovascular Sciences
- Areas of expertise: super resolution microscopy; biophysics; cardiac muscle; skeletal muscle; live cell imaging; microscopy instrument development
- Email: I.Jayasinghe@leeds.ac.uk
- Phone: +44(0)113 343 9683
- Location: 7.52a Garstang
- Website: Nanoscale Microscopy
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).
Advancing the utility of nanoscale imaging tools
Super-resolution microscopy techniques have helped unlock a number of mysteries in the Life Sciences, particularly in Cell and Molecular Biology. These techniques have classically included PALM and STORM. In my team, we have become some of the earliest adopters of the new techniques called DNA-PAINT (schematically shown) and Expansion Microscopy. Harnessing DNA-PAINT, we have achieved optical resolution of 10-15 nm, sufficient to visualise individual proteins within tightly organised signalling nanodains within cells. Ongoing work includes adaptation of these tools to improve this resolution further.
Structural basis of calcium signalling in the heart
It is primarily the spatial 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.
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.<h4>Research projects</h4> <p>Any research projects I'm currently working on will be listed below. Our list of all <a href="https://biologicalsciences.leeds.ac.uk/dir/research-projects">research projects</a> allows you to view and search the full list of projects in the faculty.</p>
- BSc (1st class Honours) in Biomedical Sciences at the University of Auckland, NZ (2007)
- PhD (Physiology) in the University of Auckland, NZ (2011)
- Fellow of the Higher Education Academy, UK (2018)
Research groups and institutes