Molecular and cellular mechanisms of selective autophagy and their relevance to ageing

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Advances in modern medicine have led to a significant increase in human life expectancy. A consequence of this has been the increase of the frequency of ageing-related diseases. Recent studies have indicated that a breakdown of the autophagy system in cells is involved in the development of ageing-related diseases. Autophagy describes the essential process of cellular self-eating. Cells use autophagy to generate materials and energy when conditions become unfavourable. They also use this process to clear damaged cellular components. Initially it was thought that autophagy was a random process but there is growing evidence it is accomplished in a highly controlled, selective and specific manner. We will use the fruit fly, Drosophila melanogaster, as a genetically modifiable model organism to investigate autophagy during ageing and how it can contribute to the selective disposal of damaged and potentially toxic cellular material which may be the cause of ageing. These mechanisms are very similar between fruit flies and humans, so the results will have direct relevance to human health.We aim to understand at molecular level how autophagy works and how specific proteins are identified to be degraded. We will then study how this process is affected during ageing and how it begins to break down and lead to age-related diseases developing.This project will make a major contribution to our understanding of the fundamental mechanisms of selective autophagy and could potentially be used in applied research aimed towards developing new strategies to fight age-related diseases and to extend lifespan.