SHAPE · SHAPE. Deciphering sarcoplasmic reticulum shaping in heart function

Cardiovascular diseases (CDs) are the main cause of death in the European Union (EU) and they cost the EU €210 billion a year. Expanding the molecular knowledge on CDs is a key factor in the struggle against them. The sarcoplasmic reticulum (SR) is one of the chief organelles involved in proper cardiomyocyte function due to its implication in calcium handling, and because of that, one of the principal therapeutic targets. SR comprises at least two different regions whose function is well known, however the molecular actors that profile it and how the correct arrangement of them is obtained remain unknown. In contrast, endoplasmic reticulum (ER) shaping and how changes in its shape affects ER function have been recently described. Due to this shape/function relationship and considering the similarities between ER and SR, it is likely that SR shape modulators are fundamental also in maintaining proper SR function. In this scenario, it is tempting to speculate that ER shape alteration is involved in the development of CDs. The aim of this project is to study how the SR shape affects its function. This ambitious goal will be achieved by bringing together my expertise in cardiac physiology with the know-how of my supervisor in ER shape/function and my co-supervisor knowledge on calcium signalling, by using the powerful genetic model Drosophila melanogaster. The results of the project will impact the cardiac function knowledge and could provide possible new therapeutic targets against CDs. Moreover, the results of the project could impact other fields of research, as well as muscular research, by expanding the understanding of SR shape/function relationship.