Goal of our yeast work

Cells are continuously exposed to changes in their environment. This is not only a challenge for single-celled organisms like budding yeast, but also for tumor cells, which can be exposed to various forms of stress including low oxygen levels, chemotherapy, radiation, and low nutrient levels. For optimal growth and survival, cells have developed mechanisms that sense environmental alterations and generate responses that maintain cellular homeostasis. We use the budding yeast Saccharomyces cerevisiae as a model organism to understand how cells cope with environmental changes, in particular nutrient stress.

Autophagy

A major response to environmental stimuli is activation of autophagy, which is a catabolic process that degrades cellular components into smaller molecules, thereby sustaining essential cellular processes. Whereas autophagy has been studied for decades, it remains unclear how cells control this process at the systems level. In particular, autophagy must be carefuly tuned, because excessive autophagy, or an inability to properly inactivate it, can be detrimental to cellular fitness.

Therefore, we performed a comprehensive study of autophagy dynamics, where we analyzed the effect of every gene in the genome both on activation and inactivation of autophagy over time at the single-cell level. This has resulted in a comprehensive dataset, AutoDRY (Autophagy Dynamics Repository in Yeast), which will be made publicly available shortly. A manuscript reporting this study has been posted on a the preprint server bioRxiv. Among other things, this study provides machine learning and bioinformatics tools for analyzing autophagic phenotypes; shows how each gene affects the kinetics of autophagy during starvation and during nutrient replenishment; visualizes how cell populations traverse the 'autophagic space' during activation/inactivation of autophagy; and provides a genome-wide map of the genetic network of autophagy-regulating genes.