Structural and functional investigation of the skeletal muscle excitation-contraction coupling complex

This project aims to understand the basic function of the skeletal muscle, and how mistakes in this function can lead to life-threatening disease. A key element of the complex biochemical process known as muscle contraction is a specific particle, named calcium ion. Both the heart and skeletal muscle tissues rely on the movement of calcium ions within each individual muscle cell. This movement occurs through specialized proteins that form ‘pathways’ or ‘channels’. When this pathway doesn’t work properly, however, there can be deadly consequences. In the heart, for example, mutations in the DNA can lead to faulty channel proteins that can no longer allow the normal passage of the calcium ions. This leads to heart rhythm disorders that can result in sudden cardiac death. How exactly the mutations cause this is not fully understood. We aim to understand this, by looking at the detailed 3-dimensional structure of the pathway, and by comparing healthy proteins with diseased versions. Because proteins are too small to see with the naked eye or even with very good light microscopes, we need to use a special tool. We will make use of a so-called ‘electron microscope’, whereby the protein is bombarded with electrons instead of light.