Grant: Discovery Grants Program - Individual

An adequate supply of oxygen is important for the survival of all tissues in all vertebrates, but is especially critical for tissues with high energy demands such as heart and brain. Hypoxic stress (low oxygen) (environmentally induced such as at altitude, in burrows and in O2 poor waters, or metabolically induced such as by exercise, digestion and reproduction) has driven the evolution of novel adaptations in animals that encounter such conditions. The key to tolerating hypoxia is to match O2 supply to O2 demand. The first step in the process of regulating O2 supply, is ventilation, and one goal of my research program is to determine why animals breathe the way they do under different conditions (at rest, sleep, exercise, altitude, dormancy, hibernation, diving, etc.). Breathing is essential for gas exchange in all large, multicellular organisms, but the mechanistic basis of respiratory rhythm generation and the manner in which the basic rhythm is modified to meet changing demands are not fully understood. We also don't fully understand how the other steps in the gas transport cascade that move O2 and CO2 between the atmosphere and the mitochondria are regulated and integrated to meet fluctuating demands in different environments. These steps include the diffusion of gases across the gills/lungs, the transport of O2 in the blood by the pumping of the heart, the capacity of blood to hold O2, and the diffusion of O2 from the blood into the tissues. All of these steps are modulated by the interaction of peripheral sensory feedback and such descending inputs as those associated with locomotion, changes in arousal state (such as sleep, dormancy and hibernation) and body temperature. By investigating the mechanistic basis of the regulatory steps in this cascade, our work provides insight into the developmental (phenotypic) and evolutionary (genotypic) plasticity of one of the most essential process for life; gas exchange. There is also another side to this equation. Matching oxygen supply and demand can be met under hypoxic conditions not only by increasing supply but also by suppressing demand. The mechanistic basis of hypoxic metabolic suppression and the manner in which it is modified in the face of changing oxygen supply are even less well understood, as is the manner in which the balance between increasing supply versus reducing demand is orchestrated. Using species differences (phylogeny), developmental changes (ontogeny) and genetic manipulations as tools, my students and I hope to determine the ways in which the mechanisms matching metabolic supply and demand have been shaped by evolution to meet the demands of vertebrates with varied life histories living in different environments.