Research project
Remodelling of structure-function relationships underlying cardiac dysfunction in ageing and heart failure: A multi-scale systems approach
- Start date: 1 October 2021
- End date: 30 September 2026
- Funder: Medical Research Council (MRC)
- Value: £1,203,472.48
- Primary investigator: Dr. Michael Colman
- Co-investigators: Dr Al Benson, Dr Matthew Lancaster
- External co-investigators: Izzy Jayasinghe, University of Sheffield; Blanca Rodriguez, University of Oxford; Esther Pueyo, University of Zaragoza; Yohannes Shiferaw, California State University, Northridge
Project title
Remodelling of structure-function relationships underlying cardiac dysfunction in ageing and heart failure: A multi-scale systems approach
Description
This project uses a combination of simulations and experiments to characterise the nature of ageing-associated remodelling of the structures of cardiac cells and tissues, and mechanistically link these remodelled structures to emergent dysfunction.
Cardiac-ageing is associated with mechanical dysfunction, which reduces the heart’s pumping efficiency and limits daily activities, and an increased vulnerability to arrhythmia, which can be immediately life-threatening.
For example, the incidence of ventricular ectopic excitation, which can act as a trigger for fatal arrhythmia events, is 17-fold higher in men aged over 60 than those aged 20-40.
Remodelling of the structure-function relationships in cardiac cells and tissues can explain both this mechanical and electrical dysfunction.
A major challenge in dissecting the mechanisms of this dysfunction is that ageing is associated with remodelling of structure-function relationships across multiple spatial scales - from the sub-cellular nanodomain right up to the whole-heart. It is ultimately the multi-scale interaction of these remodelled structure-function relationships which causes dysfunction.
This project is using a combination of experimental and simulation approaches to achieve its aims. Experiments will characterise structural remodelling at multiple scales, and simulations will provide the mechanistic link between structure and function at each scale individually as well as between scales.
Experiments include super-resolution microscopy, patch-clamp, optical mapping and MRI.
Computational models include spatial models at each scale as well as new approaches to integrated between the scales.