This proposal requests support for a Gordon Research sponsored Conference on Cobalamins to be held between Jul 6-11, 2003 at Colby College, Waterville in Maine. The field of cobalamin research has been experiencing a renaissance and important insights into the structures and functions of complex transporters and of enzymes that utilize the cofactor to effect radical or heterolytic chemistry-based transformations have been emerging over the past decade. Investigations into the biosynthesis of cobalamin have revealed that it is the most complex of any known metabolic pathway requiring in excess of thirty enzymes for its complete de novo synthesis. To complicate things further, there are both aerobic and anaerobic versions of this biosynthesis, providing a rich natural resource for evolutionary biologists to probe its early biotic origins. In addition, application of bioinformatic approaches have led to the discovery of disease-causing genes involved in cobalamin metabolism and to the identification of pathogenic mutations. Epidemiolgical studies point to an inverse correlation between cobalamin and homocysteine levels, the latter when elevated, is an independent risk factor for cardiovascular diseases, neural tube defects and Alzheimer's disease. The conference on Cobalamins will bring together, clinicians, biologists and chemists working on varied aspects of the field and provide a venue for discourse and free exchange of ideas. By combining investigators with expertise in spectroscopic methods, membrane proteins, mouse genetics and computational chemistry together with physicians with access to patient cell lines, it is expected that the meeting will stimulate collaborations and catalyze scientific progress.
