In this project, a cross-disciplinary team of scientists will uncover the mechanisms underlying how animals specialize for life in the deep ocean. The volume of the deep sea is vastly larger than all other habitats on earth combined, but only highly specialized organisms can survive its extreme conditions. How do deep-sea animals keep their cells functioning under freezing temperatures and crushing pressures -- hundreds of times that at the surface? In a surprising twist, once animals have adapted to the deep sea, surface conditions often turn extreme to them, and they fail to survive anywhere except in the deep sea. The researchers will focus on the cell membranes of deep-sea animals -- molecular structures that are very sensitive to pressure and temperature. The team will apply the latest methods in deep-ocean exploration, genomics, lipidomics, biophysics, synthetic biology, and computer modeling to uncover the molecular and cellular features that allow for survival in different marine environments. Success will lead to new knowledge about the biochemical limits of life and give insight into how environmental changes might affect diversity and abundance of marine animals. Broad preparation is an essential aspect of transformative research, because breakthroughs come when scientists integrate information from a variety of domains. Thus, this project will provide cross-disciplinary training for Ph.D. students to produce a new generation of diverse scientists who are trained in integrative approaches to biological research. The team's findings will also be incorporated into an integrative education curriculum for K-12 students in partnership with educators across the country.<br/><br/>The project uses ctenophores -- commonly called comb jellies -- as a model system to discover rules that underlie an organism's ability to tolerate the extreme conditions found in the deep sea. Many scientists have never seen a live ctenophore, yet this phylum represents an excellent model system for the study of adaptation to extreme environmental conditions. Ctenophores inhabit a wide range of temperatures (-2°C to 30°C) and pressures (1 to 700 bar), and they have convergently adapted to these conditions, with closely related species also being found in very deep and very shallow habitats. Recently it has become possible to maintain them in lab culture for several generations, and there are high-quality transcriptomes and chromosome-scale genomes available. Thin layers of tissue are essentially all that distinguishes a ctenophore from the surrounding water, so adaptation must be focused at the cellular level. The overall hypothesis driving this project is that adaptations in lipid metabolism can be used to overcome the inhibition of cell-membrane dynamics by pressure. The project combines bioinformatics, whole-animal experiments, pressurized biochemical characterization, high-pressure small-angle x-ray scattering, molecular dynamics simulations, and synthetic biology to uncover the genetic and physicochemical mechanisms by which ctenophore membranes adapt to the deep ocean. Predictions that emerge from integrated observations will be tested by engineering lipid metabolism in microorganisms. The "rules" that emerge will be relevant to marine biology, biotechnology, food science, and the physiology of animals subjected to extreme conditions.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.