Does Piezo1 help the heart sense mechanical stress?

Investigating the role of the mechanosensitive cation channel Piezo1 in the regulation of cardiac fibroblast function (Miss Nicola Blythe)

Supervised by Dr Neil Turner, this PhD student is studying how a protein called Piezo1 helps the heart respond to mechanical stress, caused by increased force of contractions of heart muscle. Cardiac fibroblasts are cells that produce ‘scaffold’ proteins to maintain the heart’s structure. When the heart is damaged and mechanically stressed, the heart tissue becomes rigid. Fibroblasts sense this damage and produce more scaffold proteins, which make the heart even more rigid – a process called fibrosis. It becomes harder for the heart to pump blood, leading to heart failure. Piezo1 is a protein that forms a hole, or channel, in the cell surface that senses mechanical signals and alters how the cell works. Dr Turner has found that both mouse and human cardiac fibroblasts express Piezo1 channels, and more are present in activated fibroblasts. Dr Turner thinks these channels sense the stiffness of the heart and activate fibroblasts. In this project, the student will find out if Piezo1 activates cardiac fibroblasts in response to mechanical stress. They will determine how both normal and mechanically stressed hearts respond differently to mechanical stress when Piezo1 channels are removed from fibroblast cells. This research will improve our understanding of how mechanical stress causes fibrosis, and may reveal targets for new drugs to reduce fibrosis in people with heart disease.