Elucidating the molecular mechanisms of diet-induced autophagy

UK has the highest level of obesity in Western Europe and nearly two thirds of its population is overweight or obese. This excess weight elevates significantly the risk of diseases, such as diabetes, heart failure and stroke, which ultimately lead to premature death. High-calorie diet is one of the causes of the rapid rise in obesity. Understanding how high-calorie diet and starvation act at the molecular level inside the cells and how they induce starvation will help us to develop dietary habits to reduce the incidence of excess weight in the population. We are using the fruit fly Drosophila melanogaster as a genetically modifiable model organism to investigate how starvation regulate the cellular process of autophagy. Autophagy is an essential cellular process that involves the degradation of cytoplasmic material through the lysosomes. Cells use autophagy to generate materials and energy when conditions become unfavourable. Autophagy is the cellular response to starvation, a process that mimics caloric restriction. These mechanisms are very similar between fruit flies and humans, so our results will have direct relevance to human health. The overall purpose of this project is to understand how caloric restriction regulate the function of autophagy-associated proteins through acetylation - deacetylation. The main objectives of the project are: 1) To examine whether starvation regulates autophagy-related proteins' aceylation/de-acetylation status, 2) To examine how acetylation mediates the interaction between autophagy-related proteins and transcriptional factors and how this represses autophagy at the transcriptional level. 3) To examine how autophagy-related proteins are re-acetylated by acetylases.
Understanding the mechanisms by which caloric restriction regulates autophagy has many benefits for clinicians and related health professionals; commercial organizations; relevant medical charities; government agencies; and the public.