FINALphagy

When an organism experiences physiological stresses, such as nutrient starvation, it activates several mechanisms to promote its survival. One of these mechanisms is autophagy, which is a catabolic pathway conserved from yeast to man that functions as a recycling system during normal physiology, and which helps provide nutrients to sustain essential cellular processes during starvation. Dysregulated autophagy is implicated in multiple diseases, such as cancer, neurodegeneration and metabolic disorders.

The project “FINALphagy” aims to fundamentally improve our understanding of autophagy by elucidating the mechanisms of how autophagy is inactivated and how this is orchestrated in an entire organism.

The project is radical since most studies have focused on how cells regulate the activation of autophagy, whereas it remains largely unknown how cells and organisms shut off autophagy in response to returning nutrient availability or as an adaptation strategy. The limited knowledge of autophagy termination is partly due to a lack of available tools and appropriate methods. Addressing these challenges will not only provide important insight in this fundamental aspect of the autophagic process, but may potentially also identify new targets for development of drugs to manipulate this phase of autophagy.

FINALphagy will develop new genetic and computational tools to quantify and manipulate the temporal dynamics of autophagy in an entire organism. We will unravel key mechanism of autophagy termination in individual cells within a tissue and dissect how this connects to systemic signaling in different genetic backgrounds. This will generate a comprehensive toolbox for time- and space-resolved manipulation and quantification of autophagy levels, produce a whole-organism map of autophagy responses at the tissue-level, and identify regulators of autophagy termination that can be of potential clinical use in autophagy modulation in relevant disease contexts in the future.

Learn more about the project here.