The overall objectives of the proposed research are: (i) to investigate the structure function relationships in biological membranes, in particular the relationship between membrane transport and its molecular structure; (ii) to reconstitute membranes from components; and (iii) to gain some insights into the basic principles underlying membrane aberrations in malignant cells. The basic experimental approach is to combine chemical, biochemical, biophysical, and genetic techniques to investigate membrane structure and transport, and to reconstitute membranes from components. We believe that our basic approach is one of the best ways to gain a systematic, deeper understanding of a complex biological problem like cell membranes. Nuclear magnetic resonance (NMR) spectroscopy will be used to investigate membrane structure and dynamics as well as conformational changes in deuterium-, carbon-13, and fluorine-19 labeled transport proteins and phospholipids in membranes during the transport process. We shall study the properties of transport proteins (recognition and translocation proteins), phospholipids, model membranes, and reconstituted membranes in relation to membrane transport. We shall also investigate the properties of the isotopically labeled as well as reconstituted membranes in relation to the properties of """"""""altered"""""""" membranes found in malignant cells. The conquest of cancer depends to a great extent on the progress made in numerous fields of fundamental biomedicine. Among the important aspects of cancer are the cell membrane anomalies, generally found in tumors. These membranes anomalies may account for several critical aspects of malignancy as well as the immunologic properties of most tumor cells. Even though we have chosen bacterial membranes for our initial studies, it is expected that the results of our proposed membrane research will contribute not only to a better understanding of some of the essential cellular processes in normal living cells but also be gaining some insights into the basic biochemical and biophysical principles underlying membrane aberrations in malignant cells.
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