There is a pressing need to comprehensively understand species' responses to environmental change. Species living close to their physiological limits are especially vulnerable to climate change. Current advances describe physiological climactic limits at the organismal level, but the cellular mechanisms that underlie the physiology of stress responses remain elisive. This proposal will integrate powerful genetic and evolutionary approaches to generate a systematic understanding of how molecular mechanisms allow organisms to counter environmental stress. The outcome is a better understanding of fundamental processes in response to the environment with far reaching implications for climate change research, biodiversity and human health.