The overall aim of this project is to define the genesis, evolution and eventual senescence of the normal red cell membrane. Long-term objectives which may accrue from these studies are the development of some understanding of the pathophysiologic mechanisms involved in hemolysis and the more general application of model information gathered on red cell membrane development and maturation towards the understanding of those processes in other somatic cells. Four complementary approaches towards our overall aim will be employed: 1) studies to isolate the genes responsible for directing the synthesis of selected red cell membrane proteins; 2) studies to define the nature of the red cell membrane in fetal and neonatal cells, and to compare it to adult cells; 3) studies to examine the nature of free radical or oxidative damage to red cell membranes during their development, circulation and maturation, and 4) studies attempting to define the senescent red cell membrane and the mechanisms of its production. A broad range of methods from the disciplines of molecular biology, biochemistry, immunology, cell biology and biophysics will be utilized in these studies which will be conducted in five laboratories, a supporting "morphologic" core, and two consulting laboratories. It is hoped that this effort to gain some understanding of the development of the red cell membrane, from its birth to its death, will eventually provide insights which will be useful for the management of hemolytic anemias and other clinical disorders where cell membrane development may be disordered.