Structure, mechanisms, regulation and assembly of ATP synthase

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Biological life depends on a source of energy. That energy comes from sunlight. It is harvested by photosynthesis in green plants, and provides the high energy components in the foods that we eat. We harvest that energy in our bodies by "burning" (oxidising) the high energy components, releasing cellular energy in a controlled way to generate the fuel of life, in the form of the molecule known as adenosine triphosphate (or ATP for short). The key steps in this process take place in the mitochondria inside the cells that make up our tissues. The mitochondria are biological "power stations" full of millions of tiny molecular turbines, the ATP synthases, that rotate rather like man-made turbines churning out the cellular fuel in massive quantities, which is then delivered to all parts of our bodies to provide the energy to make them function. We understand in great detail many aspects of how these molecular turbines work, but as yet not how the rotary action is generated. Part of this project is about providing that crucial missing information. Bacteria have similar turbines that differ is some respects from the human turbines. We want to understand these differences better, so that we can devise drugs to kill pathogenic bacteria, such as the one that causes tuberculosis, by stopping their turbines without influencing the human ones. Associated with the human turbines, but not part of the ATP making machinery, is a channel that becomes opened, for example during a heart attack, letting out the contents of the mitochondria in an uncontrolled way leading to the death of the cell. We want to understand how this pore works, so that we can help design other drugs to control the pore.