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                                                                 Associate Professor Izzy-Jayasinghe (Photo: UNSW Sydney)

Decoding sub-cellular structure-function link with super-resolution microscopy

Hosted by: Dr Steve Lee

Abstract

The advent of localisation microscopy, and more recently, expansion microscopy (ExM) has been game-changing for our group and numerous other researchers worldwide. Some of the newest analytical capabilities unlocked by these ‘super-resolution’ microscopy techniques include the visualisation of living systems (tissues, cells, and organelles) and nanometre-scale resolution, counting of single proteins and their interactions with molecular partners, and observing the heterogeneity of chemical signatures on whole populations of proteins inside the working cell.

In this seminar, I will outline how >15 years of innovation in localisation microscopy techniques such as STORM and DNA-PAINT have allowed us to decode the structural basis of intracellular signals, including fast calcium sparks in the heart. I will demonstrate how we have used these techniques, combined with image-based computational modelling, and correlative live-cell imaging, to visualise the self-assembly and regulation of arrays of ryanodine receptor calcium channels in the heart. I will share how the protein clusters observed with these methods have been found to be functionally connected (i.e. coupled) in ways that were not observed previously in the heart. I explain how the worsening heterogeneity and re-organisation of such protein underpins the cellular pathologies in the failing heart. 

Further, this seminar will focus on the innovations that my team have made in the new(er) super-resolution microscopy concept known as expansion microscopy (ExM). ExM is a method whereby a molecular-scale imprint of any biological structure can be physically inflated using hydrogels to achieve nanometre-scale resolution in imaging. I will outline how the new suite of re-purposed molecular probes, high-throughput and error detection tools have allowed us to deploy ExM to study the molecular interactions and nanoscale features of cellular structures as endosomes and neuromuscular junctions.   

Biography

Izzy is an Associate Professor and Department Head of Molecular Medicine, UNSW, and a UKRI Future Leader Fellow at the University of Sheffield (UK). She was awarded her PhD in 2011 at the University of Auckland for the early work applying localisation microscopy (STORM) to visualise the cardiac ryanodine receptor. Following two postdoctoral positions in the Universities of Queensland and Exeter, Izzy has led the Signalling Nanodomains Lab in Leeds, and more recently in Sheffield and Sydney. Over the past nine years, Izzy and her team have specialised in correlative microscopies and some of the more recent super-resolution approaches such as expansion microscopy to study the intracellular calcium signalling machinery in excitable cells. As a part of her UKRI fellowship, Izzy’s team in Sheffield have been developing and refining the tools, probes and analysis approaches that advance the uptake and validation of expansion microscopy. Izzy is a Fellow of the Royal Microscopical Society and works as an Associate Editor for The Royal Society’s Open Biology journal to champion sustainable academic publishing models. In 2023, she was named as one of New Zealand’s “40 under 40” as a ‘disruptor and innovator’. Outside of the research work, Izzy has worked to raise awareness of the lack of inclusion and equity in the high-education and STEM sectors through engaging with funding councils and the all-party parliamentary groups in the UK and Ireland.