Evolution of thermogenic mechanisms in brown adipose tissue: exploring the origin and ecophysiological diversity

Brown adipose tissue (BAT) is a fascinating evolutionary outcome that allows generation of endogenous heat through mitochondrial uncoupling protein 1 (UCP1), thereby enabling small eutherian mammals to survive the cold. Yet, it is still unknown how evolutionary selection has shaped BAT and UCP1-dependent thermogenesis.

Most biomedical motivated research focuses on mice, neglecting nature’s diversity of thermoregulatory strategies that provides the “blueprint” to reconstruct the molecular evolution of thermogenesis.

Here, we will study exciting new CRISPR-Cas generated UCP1 knockouts of non-eutherian species to explore the physiological role of UCP1-dependent thermogenesis prior eutherian evolution and directly compare UCP1 functionality in novel cellular systems.

We will delineate the origin and evolution of UCP1-dependent thermogenesis by combining state-of-the-art metabolic phenotyping, ´omics´ and bioenergetic technologies.Specifically, this research project aimsto unravel the physiological role and ancient function of UCP1 prior to thermogenesis in ectotherms using a novel zebrafish UCP1 knockout;to determine whether the role of UCP1 in marsupials, which are non-eutherian mammals, is thermogenic or not, using primary opossum fat cells and exploring a new, unique UCP1-knockout opossum;to identify the molecular adjustments of UCP1 during evolution and ecophysiological adaptation by directly testing protein variants in a customized cellular test system.