Diverse physiologic actions of gases such as O₂, NO, CO, CO₂, H₂S have attracted great interests, while mechanisms for the gas reception and their roles for regulating biological systems as a whole remain largely unknown. Recent observations unveiled by metabolome analysis suggest that rate-limiting enzymes of major metabolic pathways with metal-centered prosthetic groups might sense gases and trigger post-translational modification of macromolecules, suggesting their crucial roles for stress-responsive adaptation involving management of energy metabolism and tissue repair and remodeling. Overcoming technical difficulties to mine receptors for gases, to visualize gas-mediated signaling events in vivo and to examine their effects on metabolic systems deserves further studies to utilize outcomes of Gas Biology for medicine. This proposal challenges to dissect the gas-responsive mechanisms for bioregulation through multidisciplinary approaches involving advanced imaging massspectrometry, nanobiotechnology, computational biosimulation and development of genetically engineered humanized animal platforms with multimodal intravital microscopy.