Every second, millions of tiny molecular turbines inside your cells spin to generate the fuel that keeps you alive—and scientists still do not fully understand how they turn. This project tackles two gaps in our knowledge of ATP synthase, the enzyme that produces most of the body’s chemical energy. First, researchers want to work out exactly how the turbine’s rotary motion is generated, a fundamental missing piece in the picture of cellular energy production. Second, they aim to compare the human turbine with similar ones in bacteria, including the bacterium that causes tuberculosis. Understanding these structural differences could reveal how to stop bacterial turbines without harming human ones. If successful, this fundamental science could lay the groundwork for new antibiotics that target ATP synthase in pathogens like *Mycobacterium tuberculosis*. It could also help researchers design drugs to control a separate channel associated with the human turbine—a pore that opens during a heart attack, releasing mitochondrial contents and killing heart cells. Blocking that pore could limit tissue damage. This is primarily curiosity-driven research into a core biological machine, but past work on similar molecular motors has already led to drugs and medical insights that no one predicted at the outset.
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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.
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