Supervisor

Suitable for

Abstract

Co-supervised by Christopher Toepfer

Cardiomyocytes are the cells responsible for generating contractile force in the heart. They are highly adaptable and alter their function in response to many stimuli (electrical stimuli, calcium, contraction, organisation of cellular structures, metabolism, and transcriptional signatures). These processes are all interrelated and dynamic in live cardiomyocytes, but we lack the ability to visualise them simultaneously and correlate them in real-time. We have previously developed specialised software [1, 2] to automate high-throughput analysis of cardiomyocyte function. However, these are not optimised to work with large files and cause data fragmentation as they do not work in tandem.

To develop novel software solutions for the analysis of cellular heart function for three channel, high throughput, resolution, and frame-rate imaging and analysis of beating cardiomyocytes.

Imaging live cardiomyocytes during contraction and relaxation necessitates high-frame rates (100s of FPS), which must be twinned with high resolutions (<70 nm per pixel), also allowing the simultaneous analysis of multiple well plates for high-throughput. In collaboration with the Oxford Department of Cardiovascular Medicine, and building on extensive datasets of high-resolution, high-rate fluorescent imaging of live cardiomyocytes, students taking this project will develop novel open-source software solutions integral to discovery and translational cardiovascular research. Different research options would be available, such as:

• optimisation and/or development of novel algorithms for the analysis of sarcomere contractility and relaxation;
• development of an analysis pipeline for masking, segmenting, and fitting action potentials from a variety of cellular systems;
• development of an analysis pipeline for the automated analysis of mitochondrial shape, abundance, and cellular metabolites.

[1] CalTrack: High-Throughput Automated Calcium Transient Analysis in Cardiomyocytes. https://doi.org/10.1161/CIRCRESAHA.121.318868

[2] SarcTrack: an adaptable software tool for efficient large-scale analysis of sarcomere function in hiPSC-cardiomyocytes. https://doi.org/10.1161/CIRCRESAHA.118.314505