The world is changing at an unprecedented pace. Climate change projections predict both higher average temperatures and a greater frequency of extreme weather events (e.g., hot, cold, dry, etc.). The ability of animal populations to survive such changes rests on how much genetic and physiological variation they possess for environmental tolerance. As the climate changes, predicting the responses of animal populations to thermal change will require understanding the consequences of thermal stress at fine scale genetic and physiological levels. Thus, the main objective of this project is to characterize mechanistically the genetic and physiological bases of thermotolerance with the long-term goal of predicting and monitoring mechanistic changes in animal populations in real time. The model fruit fly, Drosophila melanogaster, is well suited for this research because it is widely distributed and shows the capacity to adapt to novel thermal conditions in the field and laboratory while also being genetically and physiologically tractable. The immediate aims of this project are to: 1) Identify genomic regions harboring natural genetic variation affecting cold tolerance in nature; 2) Test current hypotheses about biochemical and physiological mechanisms underlying the evolution of cold tolerance; and 3) Integrate the complex data sets generated by genomic screens and hypothesis-directed physiological and biochemical assays to identify the candidate genes that matter for the evolution of cold tolerance. Linking whole-organism thermotolerance and physiological mechanisms of tolerance with genetic variation in these candidate genes will provide a foundation for understanding the capacity for animal populations to adapt to a changing climate. The project will also provide educational opportunities for young scientists at multiple levels.