Form, Function, Mechanism: How Cellular Physiology Controls Heart Development

Cardiac form and function are inextricably linked. In the heart, disease is associated with changes in both physiology and morphology, although mechanistic insight into this relationship is complicated. Early heart development provides a unique model to explore how the onset of function impacts form. My research programme will use heart development to identify how cellular physiology influences gene expression and cell fate decisions, in order to identify mechanisms with therapeutic potential. To address my research vision, I will temporally define the transcriptional and physiological characteristics of cardiac progenitors as they generate distinct cardiac lineages during the onset of function. I will explore how disrupting function influences form in vivo. Furthermore, and aiming to translate my findings, I will develop in vitro human models, focusing on the generation of distinct cardiac progenitor types identified in the human embryo, enabling me to connect descriptive genomic insight with functional relevance. Functional perturbation experiments will identify pathways which integrate different components of contraction with gene expression, regulating heart development and disease states. My work will enhance models of human heart development and provide insight into the relationship between form and function, aiding in the development of cell-based approaches for cardiac regeneration and heart disease.