Regulation of Caspase Activation

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In animals, the behaviour of the cells that make up the body must be tightly controlled in time and space. Part of this control stems from a built-in ?auto-destruct mechanism?, called apoptosis. This mechanism is carried within each cell, and through it the cell is instructed to die if it becomes potentially harmful or is no longer required. In order for an animal to remain healthy, apoptosis must be tightly regulated. Indeed, numerous human diseases result from the loss of this regulation. In cancer, for example, mutated cells escape apoptosis, allowing them grow and divide inappropriately; the consequence is a tumour. On the other hand, when brain cells undergo apoptosis inappropriately, neurodegenerative disease results. Thus maintenance of the correct balance of apoptosis is vital, but the molecular mechanisms underlying this process are not well understood. Our aim, therefore, is to unravel the molecular machinery that controls apoptosis. Our work concentrates on a group of highly specialised enzymes called caspases, which function as the engines of the apoptotic programme. By elucidating how caspases become activated under normal conditions, we will gain a better understanding of how apoptosis becomes deregulated in human diseases.