Adhering to the original philosophy that has guided the Alcohol Research Center from its inception, we bring together researchers with a background in biophysics, biochemistry, cell biology, molecular biology and pathology around the central theme of """"""""Alcohol and the Cell"""""""". The common focus of the different research components remains the elucidation of (1) the relationship between the structural and functional effects of ethanol on cells and subcellular structures, (2) the adaptations occurring during long-term exposure of the organism to ethanol, and (3) the molecular basis for irreversible cell injury associated with long- term ethanol intake. Studies focus on a variety of different tissues, including liver, heart, brain, erythrocytes, cell lines of different origins and model membrane systems. Techniques to be used include electron paramagnetic resonance, 13C-, 2H- and 31P nuclear magnetic resonance, fluorescence microscopic imaging of single cell calcium transients, electron microscopy, HPLC separation of lipids and lipid derivatives (both on an analytical and preparative scale) capillary gas chromatography and molecular biological techniques. Individual projects focus on the thermodynamics of alcohol-membrane interactions; the changes in phospholipid metabolism induced by chronic ethanol treatment; effects of ethanol on membrane-protein kinase C interactions at the membrane surface; changes in cellular signal transduction pathways after chronic ethanol treatment; effects of ethanol on excitation-contraction coupling in the heart, and on the activity of the 1GF-I receptor in human glioma cell lines; effects of chronic ethanol exposure on the sensitivity to mitochondrial inhibitors and anoxia in relation to cell injury; and the response of the creatine-kinase transfected liver to redox stress in alcohol metabolism, as measured by 31P NMR. We expect that these studies will contribute to elucidating the relationship between ethanol-induced alterations at the molecular and cellular level and the development of ethanol-related diseases.
