Fasting has been part of health practices from ancient times to the present. This tradition may be partially rooted in a cellular process we are now beginning to understand in modern scientific terms. One of the major cellular responses during fasting is the activation of the lysosomal degradation pathway of autophagy, a process in which the cell digests its own components. By this mechanism, the cell not only provides nutrients to maintain vital cellular functions during fasting but can also rid the cell of superfluous or damaged organelles, misfolded proteins, and invading microorganisms. Interestingly, autophagy is now emerging as a central biological pathway which functions to promote health and longevity. Faithful autophagy is pivotal for cell survival under stress conditions as nutrient limitation and autophagy have been found to play an important role in several human diseases including neurodegeneration and cancer.

One of the key regulators of autophagy is the target of rapamycin (TOR) kinase, which is the major inhibitory signal that shuts off autophagy in the presence of nutrients and growth factors. Under nutrient limiting conditions, when TOR kinase is inactive, autophagy is induced, which results in the sequestration of cytosol and organelles into a double-°©?membrane compartment followed by their subsequent delivery to the vacuole/lysosome for breakdown and recycling.

Our understanding, however, of the mechanics of autophagy regulation, as well as its role in human health and disease, is still at an early stage. The major upstream regulator of autophagy is the Atg1 kinase complex, which is believed to receive directly the nutrient signal from TOR, and in response, to activate or inhibit the autophagic machinery.

• We are studying the role and function of Atg1 kinase in the regulation of autophagy in budding yeast, using phospho-°©? proteomic approaches, genetic screening techniques as well as modern biochemical and cell biological methods. We are mainly focusing on two questions:

• How does the Atg1 kinase regulate autophagy function, e.g. what are the physiological substrates?
• How is the Atg1 kinase regulated?

These approaches aim in understanding the mechanistics of a central player in autophagy regulation. Since the Atg proteins are highly conserved in other eukaryotes, this work will also help us to better understand diseases associated with autophagy misregulation.