Cells are able to sense and respond to oxygen deprivation (hypoxia) by modifying their metabolism to cope with low oxygen levels. The evolutionarily conserved hypoxia response plays a crucial role for survival under changing environmental conditions, as well as in diseases, including cancer, ischemia, and stroke. In Drosophila larvae, hypoxia induces tracheal growth and branching, resembling angiogenic responses induced by hypoxic tumor cells. We use hypoxia-induced tracheal growth as a paradigm to address the interrelation between cellular metabolism and gas exchange. To this aim we developed tools to visualize hypoxic signaling in living larvae under changing physiological conditions (hypoxia, hyperoxia, oxidative stress), as well as upon perturbations of mitochondrial metabolism and cellular growth control. We plan to apply our hypoxia reporter system in high-throughput screens (using large-particle flow cytometry) to identify genes and compounds that modulate hypoxia responses. The aim of this work is a better understanding of hypoxic effects during development, with implications for tumor metabolism and the regulation of angiogenesis by metabolic cues.