Learning about silent genes that could help the heart repair itself

Investigating the functional role of the noncoding genome during epithelial-to-mesenchymal transition to enable cardiovascular regeneration

Damage to the heart muscle caused by a heart attack cannot be repaired. This is because the adult heart has a limited ability to grow new muscle cells. Recently, Dr Vieira has shown that the heart attempts to repair itself after injury by using similar processes to those used in the embryo to build the heart before birth. Cells from the outer layer of the heart, called the epicardium, become switched on in a process called the epithelial-to-mesenchymal transition (EMT). However, this does not happen for long enough to support new blood vessel and muscle growth. In this fellowship, Dr Vieira hopes to understand the EMT process in greater detail. He is focusing on a protein molecule called Wt1 that controls the EMT process. He will study the parts of our genes that control Wt1 function and, in particular, will look at regions of our DNA that did not previously appear to have a role (called non-coding or silent sequences). These sequences might have been important in switching on genes needed for development but they are switched off when we no longer need them. By creating a ‘blueprint’ of these non-coding sequences that influence the EMT process in the heart, it might be possible to switch on the genes again to help the heart regenerate.