Meeting Abstract
Marine mammals exhibit dramatic physiological adaptations and offer unparalleled insights into mechanisms that drive convergent evolution on a short time-scale. Some of those adaptations (i.e. extreme tolerance to hypoxia, prolonged food deprivation) challenge established principles of matching metabolic supply and demand. Non-targeted omics studies have begun to uncover the genetic basis of such adaptations, but tools for testing their functional significance are currently lacking. A powerful approach for understanding the molecular etiology of physiological adaptation is cellular modeling, which is essential for accelerating genome-to-phenome research in organisms in which transgenesis is impossible. Gene perturbation in primary cells can directly evaluate whether positive selection or gene loss confers functional advantages such as hypoxia or stress tolerance. Hence, we have established ex vivo systems (skeletal muscle myotubes, flow-adapted endothelial cells) to conduct functional studies that can provide the missing link between genome- and organism-level understanding of physiological adaptation in marine mammals. Using these systems, we are starting to uncover the adaptive responses that drive stress tolerance in elephant seal muscles, which can switch metabolic pathways to support ATP production during chronic exposure to glucocorticoids. We are also dissecting the molecular drivers of hypoxia and oxidative stress tolerance in seal endothelial cells, which face constant fluctuations in oxygen tension derived from the diving response. Finally, we are developing adipocyte cultures from mesenchymal stem cells and muscle cells from reprogrammed skin cells to study the molecular drivers of metabolic adaptation in less accessible species.
