Showcasing the recent and ongoing DNA-PAINT experiments at the Edinburgh Super Resolution Imaging Consortium Symposium

Isuru attended the second annual Edinburgh Super Resolution Imaging Consortium (ESRIC) symposium, held this year at the Institute of Genetics and Molecular Medicine (IGMM) of the University of Edinburgh (UoE). His talk on the Molecular-scale imaging of ryanodine receptors at both the cell surfaces and interiors with the adaptation of DNA-PAINT was well-received by a range of researchers based in Edinburgh and regionally in Europe.

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Highlights from this meeting included a number of world class investigations led by research fellows and academics in UoE and Heriot Watt University. Of note, were Dr Colin Rickman’s talk on using naturally occurring enzymes as super-resolution imaging probes, Dr Lynn Paterson’s adaptation of optofluidic devices and optical tweezers for developing novel optical tools for cell biology. The plenary speaker was Prof Christophe Zimmer (from Institut Pasteur) who spoke about the adaptation of artificial neuronal networks (a tool called ANNA-PALM) to speed up super-resolution microscopy and demonstrate high throughput imaging of structures such as microtubules, nuclear pore complexes and mitochondria. We now eagerly anticipate his paper on ANNA-PALM out in press very soon.

The conference was organised by Dr Ann Wheeler and colleagues of the ESRIC and showcased their world class line up of microscopy platforms including a state-of-the-art Nikon STORM and SIM instrument and a Leica STED system.

Our research featured on the news of local TV station: ‘Made in Leeds’

On the back of our recent publication in Cell Reports, our research has enjoyed a wide ranging body of TV coverage. This included 20+ online newspapers and science & technology websites. Among this coverage, was a brief recording for the local television station Made in Leeds which was featured on the 6:30pm news on 11/1/2018. 

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Here is the link to a clip where Isuru is explaining the context and the value of the super-resolution microscopy technology in studying both healthy and disease physiology of the heart. Featured in the video, was Miriam during one of her imaging experiments.

Press coverage: “New technique offers ‘perfect window’ to examine causes of heart disease”

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Recent work of researchers from the Universities of Exeter, Leeds and Cambridge has been featured in a number of press reports.

In particular, the Yorkshire Evening Post refer to the recently published paper in Cell Reports in their statement that “A pioneering new technique could boost the understanding of the causes of heart disease, a study suggests.”

Professor Christian Soeller, based at the Living Systems Institute at the University of Exeter expands upon the pioneering nature of this research, stating: “Slightly more than a decade ago nobody thought that we would ever see individual molecules with light, the resolution just seemed insufficient to resolve such fine detail. Since then an astonishing array of new tricks has been devised. In our latest advance, the use of synthetic DNA has been critical – the deep understanding of the chemistry of DNA we have today makes it an enormously versatile tool.”

Dr Isuru Jayasinghe, at the University of Leeds, has provided context to this research in regard to heart failure, having said that: “This new super-resolution microscopy tool gives us the perfect window to visually examine the individual protein changes within heart cells’ molecular machinery which lead to heart failure. At present, none of the treatments or therapies provided to heart failure patients specifically target the signalling stations – nanodomains – within the cell, which the evidence overwhelmingly suggests are a major cause of heart failure. We believe that by visualising these signalling structures at this level of detail using super-resolution microscopy we can help guide investigations into how we can target or repair these molecular machines and thus, in the long term, help patients to overcome heart disease.”

Here at the University of Leeds, Dr Isuru Jayasinghe’s group is utilising multiple super-resolution microscopy techniques to reveal further the fine structural properties of the heart within health and disease.

Read more at: https://www.yorkshireeveningpost.co.uk/news/regional/new-technique-offers-perfect-window-to-examine-causes-of-heart-disease-1-8948322″

See the University of Leeds Science News page  http://www.leeds.ac.uk/news/article/4167/pioneering_technique_could_boost_understanding_of_heart_disease

European Pharmaceutical Review:  https://www.europeanpharmaceuticalreview.com/news/71582/powerful-technique-study-nanodomains/

Medical Xpress: https://medicalxpress.com/news/2018-01-technique-boost-heart-disease.html

EurekAlert: https://www.eurekalert.org/pub_releases/2018-01/uoe-pnt010918.php

 

New paper “True Molecular Scale Visualization of Variable Clustering Properties of Ryanodine Receptors” now out on Cell Reports

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Our latest paper together with Christian Soeller’s group is now available with open access. In this paper, we utilise the recently-described DNA-PAINT technique to achieve optical resolutions of ~10 nm as a clear improvement over the more widely used dSTORM super-resolution technique.  With the improved resolution, we were able to visualise and ‘count’ individual proteins which are clustered tightly within intracellular signalling nanodomains in muscle cells of the heart. From this analysis, we learned that the giant ryanodine receptor calcium release channels are organise more loosely and heterogeneously than previously thought. It also appeared that from cluster to cluster, their calcium release properties may be regulated more differentially by varying degrees of co-clustering with regulatory protein junctophilin-2. The study itself was also a demonstration that the enhanced resolution and the new protein ‘counting’ tools are promising new tools for studying molecular-scale biophysics in excitable cells.

The picture above illustrates, with correlative image, the remarkable improvements made by the recent dSTORM and DNA-PAINT techniques over traditional optical microscopy methods like TIRF which were state-of-the-art only ~ 13 years ago.