This award will facilitate cooperation between Professor Donald M. Marcus, Baylor College of Medicine, and Dr. Akemi Suzuki, The Tokyo Metropolitan Institute of Medical Science, Japan, and colleagues in both countries working with them. They will collaborate in a study of the molecular basis of the interaction between certain carbohydrate antigens and the specific antibodies that "recognize" them. The work is of biomedical significance because of the protection such antibodies provide against microorganisms, and because of their role in blood transfusion and organ transplantation. The researchers will carry out experiments aimed at learning the sequence of amino acids and the molecular geometry in that portion of the antibody responsible for binding to the carbohydrate. Using the technique of site-directed mutagenesis, they will alter selectively the amino acid sequences in the antibody molecule, and observe the resulting effect on the binding. They will also employ nuclear magnetic resonance (nmr) studies and computer modeling in this effort to better understand the structure of the antibody combining site. Professor Marcus is an immunologist, with expertise in determining the structure of immunoglobulin genes. His Japanese colleagues are biophysicists with considerable experience in the use of nmr in determining the three-dimensional structures of carbohydrates and proteins. The complementary strengths of the two groups will permit a multidisciplinary approach that should enhance an understanding of the mechanism of the antibody-carbohydrate interaction and, more generally, provide additional information on the characteristic specificity of antigen-antibody reactions.
