An organism’s evolutionary viability depends on its ability to respond to various environmental challenges. These challenges can range from highly complex ecological rearrangements to seemingly simple changes such as the lack of a particular nutrient. Even for these “simpler” changes, the responses of an organism often involve profound physiological reorganization. In bacteria, for instance, shifting from a nutrient-rich to a nutrient-deprived environment causes dramatic changes in their physiology. In such a shift, machinery that supports exponential growth becomes poorly suited for survival in a non-growing state. Thus, bacteria must reshape their proteome, condense their DNA, etc., to better cope with the new environment. These responses are inherently variable yet reflective of bacterial regulatory programs shaped by evolution. Variability underlies bet-hedging strategies, but it is unclear how it arises and determines the survival of bacteria in a stationary phase. During my postdoc in the van Nimwegen group, I aim to identify quantitative rules governing physiological rearrangements and gene expression variability at the entry into the stationary phase. By combining experimental and modeling work, I will investigate the relative contribution of both passive processes (e.g., exhaustion of intracellular resources) and active regulatory responses (e.g., targeted protein degradation, up- and down-regulation of gene expression) during the transition into the stationary phase. Besides ecology and evolution, the physiology of bacteria in the stationary phase shapes bacterial responses to antibiotics, which makes understanding the mechanisms of growth arrest clinically relevant as well.