Our overall goal is to develop knowledge, both descriptive and explanatory, of the phenomena of tolerance and the process of adaptation by the lung to unusual environments (hyperoxia and hypoxia) and stresses (dietary manipulation). Our approach is predicated on the notion that, by virtue of evolutionary pressures, we are now presented with an organ (lung) whose capability of tolerating stresses and adapting to change without incurring serious damage is better developed, and hence more important for the preservation of its gas-exchange structure and function, than is its ability for repair and replacement of seriously damaged functional units. We therefore intend to extend our long standing interest in lung protein metabolism and lung structure to the expansion of new ideas, regarding use of the processes and phenomena of imprinting, critical periods, and plasticity, to the generation of increaased long term tolerance and adaptation by the lung to unusual environments and stresses. We hope to achieve our goals by 1) continuing descriptive studies of imprinting, critical periods, and plasticity in lung development, and, 2) by performing experiments to elucidate the molecular and cellular basis of the lungs tolerance and adaptation to stress. We will apply techniques and concepts of biochemistry, morphometry and cell physiology to understand these aspects of lung physiology. We think our studies represent exciting new areas of lung physiology that have yet to be explored, which will eventually delineate safe ways to manipulate the lungs potential for tolerance and adaptation.
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