Decoding atrial fibrillation mechanisms using animal models and integrated functional–structural mapping of atrial cells

Atrial fibrillation (AF) is driven by complex electrical and structural changes within the atria, yet current therapies remain limited by an incomplete understanding of the underlying cellular mechanisms. This PhD project aims to unravel the interplay between atrial electrical remodelling, disrupted calcium (Ca²⁺) dynamics, and subcellular structural changes in AF using a well-established rabbit model induced by rapid atrial pacing (RAP).

Using this animal model, we will employ high-resolution optical mapping to characterise electrical remodelling across atrial tissue, including action potential propagation, conduction velocity, and AF inducibility. In parallel, atrial cellular Ca²⁺ dynamics—including spontaneous Ca²⁺ sparks and global Ca²⁺ waves—will be recorded in isolated atrial myocytes to assess how subcellular signalling contributes to arrhythmogenesis.

To link structure and function, the project will apply cutting-edge 3D super-resolution imaging to visualise and quantify atrial tubular networks (t-tubules and a-tubules) and their relationship with key Ca²⁺ handling proteins (e.g., Cav1.2, RyR2). Structural modelling of the spatial distribution and density of tubules will be compared between control and AF atria, providing a comprehensive view of how disrupted microarchitecture contributes to impaired excitation-contraction coupling.

This integrative approach—combining in vivo models, functional mapping, and structural imaging—will offer novel insights into AF mechanisms and inform the development of more targeted, mechanism-based therapies.

This project is eligible for funding but is subject to eligibility criteria & funding availability.

Page expires: 24 July 2026