The ultimate aim of this research program is to study certain structural features of ferritin and relate these to the mechanisms by which the protein incorporates, stores and ultimately mobilizes iron. Experiments have been designed to probe the overall 3-dimensional structure of the protein and aspects of its subunit structure. Environmental perturbants, and in particular some denaturants will be employed and their effects on the physical and chemical properties of the protein will be monitored. Some of the primary physical techniques to be used during this study include photoelectron spectroscopy and circular dichroism, and attempts will be made to further the theory and development of these methods for more general application in the study of biomolecules. The mechanism of incorporation of phosphate into ferritin and its participation in the iron loading process will be examined in the context of an approach to ferritin biosynthesis. Ferritins obtained from various tissues in normal and diseased states will be compared on a structural basis and also compared to normal ferritin. We will attempt to gain insight into details of the role of ferritin in iron metabolism in these tissues.