Molecular mechanisms of selective autophagy during the course of ageing

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 proteolytic cellular machinery of autophagy in cells, is involved in the development of ageing-related diseases. Autophagy is an essential catabolic process that involves the degradation of cytoplasmic material through the lysosomal pathway. Cells use autophagy to generate materials and energy when conditions become unfavourable. They also use this process to clear damaged cellular components. We will use the fruit fly Drosophila melanogaster as a genetically modifiable model organism to investigate the mechanisms of interplay between endosomal trafficking and selective autophagy during ageing in vivo. These mechanisms are very similar between fruit flies and humans, so the results will have direct relevance to human health. The main objectives of the project are: 1) To examine the interaction between autophagy-related proteins and proteins that regulate endosomal trafficking 2) To examine whether phosphorylation mediates and defines the above interactions 3) To examine how endosomal trafficking mutants regulate ageing through autophagy.