SHAPE aimed to uncover the role of sarcoplasmic reticulum (SR) morphology in cardiomyocyte and heart function.
Cardiac myocytes, the contractile cells of the heart, are highly differentiated and structurally specialised cells whose primary function is to sustain cardiac contractility and, ultimately, effective heart pump function. Central to this process is the SR, a specialised form of the endoplasmic reticulum (ER) that orchestrates calcium cycling—a fundamental mechanism for excitation–contraction coupling. Although the morphology and dynamics of the ER have been extensively studied, the specific proteins responsible for shaping and maintaining the unique architecture of the SR in cardiac cells remain largely unknown. This represents a significant gap in our understanding of cardiac physiology.
From a broader perspective, cardiovascular diseases remain the leading cause of mortality in Europe and globally, placing substantial pressure on healthcare systems and economies. The European Union and national research strategies emphasise the need to reduce the burden of heart disease through improved mechanistic understanding, early detection of dysfunction, and the identification of new therapeutic targets. In this political and strategic context, deciphering the molecular determinants of SR structure is not only scientifically relevant but also aligns with major public health priorities.
The overarching objective of SHAPE is therefore to identify the molecular players involved in SR establishment and morphology and to evaluate how alterations in these components affect cardiomyocyte and heart function. Using the powerful genetic model Drosophila melanogaster, I investigated the four best-characterised ER-shaping proteins, discovering that at least two of them are essential for proper cardiac performance. These findings highlight previously unrecognised molecular determinants of SR integrity and suggest new pathways that may be implicated in cardiac dysfunction.
By uncovering the proteins responsible for shaping the SR, this project provides foundational knowledge that may contribute to the development of future diagnostic markers or therapeutic approaches targeting subcellular structural defects. Understanding SR morphology is essential for interpreting early cellular changes that precede heart failure, making this research highly relevant for early-stage detection strategies and translational cardiology.
In summary, this project sets the scene for a deeper understanding of how intracellular structural organisation contributes to heart function, addressing a critical scientific gap while aligning with broader political and societal needs to combat cardiovascular disease.
