Optical Interrogation of Sub-Cellular Cardiac Signalling in Atrial and Sino-Atrial Node Arrhythmias At High-Spatiotemporal Resolution. (360G-Wellcome-109371_Z_15_Z)

£752,493

Atrial fibrillation (AF) is the most frequently encountered arrhythmia, associated with increased morbidity and mortality. It is known that lysosomes are actively involved in cardiac calcium regulation. I hypothesize that calcium contribution from the lysosomes is important in atrial function and perturbations in lysosomal calcium in disease processes can lead to AF initiation and/or maintenance. I propose a multi-faceted study to investigate sub-cellular anatomy, especially spatial localisa tion of organelles, and the role of lysosome mediated calcium signalling in normo- and patho-physiology. Along with pharmacological interventions, we will develop optogenetic probes to specifically control lysosomal calcium release to investigate these mechanisms. On the mechanistic side,the aim is to develop a new imaging method capable of measuring cellular and subcellular calcium events in 3D. This will be validated using cell culture models and high-speed optical mapping, which can be manipu lated to investigate arrhythmogenesis. Using fixed tissue from healthy/AF, we will perform proteomics and structural studies (MRI, electron microscopy).This will inform pharmacological and tissue engineering methods for more focussed research. The results from this study will allow a better understanding of the basic biological mechanisms of sub-cellular calcium signalling and the aetiology of AF directly relevant in the development of new treatment therapies.

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Grant Details

Amount Awarded 752493
Applicant Surname Burton
Approval Committee Sir Henry Dale Fellowship Interview Committee
Award Date 2015-10-21T00:00:00+00:00
Financial Year 2015/16
Grant Programme: Title Sir Henry Dale Fellowship
Internal ID 109371/Z/15/Z
Lead Applicant Dr Rebecca-Ann Burton
Partnership Name Royal Society/Wellcome Trust Sir Henry Dale Fellowship
Partnership Value 752493
Planned Dates: End Date 2024-03-05T00:00:00+00:00
Planned Dates: Start Date 2015-12-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East
Sponsor(s) Prof Nigel Emptage