Final act of the autophagy symphony: Whole-organism orchestration of autophagy termination

Introduction

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.

Importance of Autophagy

Although autophagy is an intensively studied process that plays a major role both in normal development and in a wide variety of diseases, several important aspects of autophagy remain to be elucidated.

Knowledge Gaps

For instance, whereas the vast majority of studies have focused on how cells regulate the activation of autophagy, it remains largely unknown how cells and organisms shut off autophagy in response to returning nutrient availability.

Challenges in Research

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 into this fundamental aspect of the autophagic process, but may potentially also identify new targets for the development of drugs to manipulate this phase of autophagy.

Project Goals

In FINALphagy, I will develop new genetic and computational tools to:

1. Quantify and manipulate the temporal dynamics of autophagy in an entire organism.
2. Unravel key mechanisms of autophagy termination in individual cells within a tissue.
3. Dissect how this connects to systemic signaling and behavioral changes.

Expected Outcomes

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 conceptualize our understanding of the dynamics of autophagy regulation in an entire organism during changing nutrient levels.