Can 3D heart muscle models reveal new ways to treat heart conditions?

High resolution structure determination of native cardiac actin-tropomyosin-troponin filaments ± Ca2+ and of myosin binding protein C bound to actin

For our hearts to beat and pump blood around the body, heart muscle needs to contract. Under the microscope, we can see that heart muscle is made up of two sets of filaments – thin and thick – which are made from several different proteins. When the body sends a signal to the muscle to contract, calcium binds to one of the proteins on the thin filament, and the proteins in the thin filament move. Scientists have a general idea of how this process works, but they don’t understand how the proteins interact in detail. Dr Danielle Paul was previously a BHF-funded heart researcher at the Institute of Cancer Research (ICR) developing techniques to study the intricacies of heart muscle, before having a career break to raise her young family. She has now been awarded a BHF Career Re-entry grant to return to her research career at the University of Bristol, where she’ll work with world-leading heart and imaging researchers and have access to state-of-the-art imaging facilities. She hopes to progress to a senior research position in Bristol within five years, and continue studying heart muscle structure, function and disease. Dr Paul and her colleagues use powerful microscopes to study the structure of heart muscle filaments, and work out how the individual proteins in the filaments move and rearrange when muscle contracts. They take pictures of the filaments when they are switched on and off and create a 3D movie of contraction, also highlighting the proteins that change their shape and position. They will now work out how to make these movies even more detailed. The research team will use these movies to understand why alterations in proteins lead to many inherited heart diseases, and how drugs can be designed to treat them by fitting into a certain shape in a protein’s surface. This research may unravel how things start to go wrong in these conditions, and ultimately may reveal how we can use treatments to return the heart muscle to normal.