This project seeks to understand the molecular mechanisms by which fucose alpha (1,2) galactose (Fuc alpha (1,2)Gal) saccharides influence recognition and communication between nerve cells in the brain. Several lines of evidence suggest that Fuccx (1,2) Gal saccharides play an important role in modulating the connections between nerve cells important for long-term memory. However, relatively little is known about their precise structure or function in the brain. The proposed research combines chemistry and neurobiology to identify the molecular components -- i.e., fucosyl saccharides, glycoproteins and lectins -- and to study the mechanisms by which they regulate the flow of information across the synapse. ? ? The specific aims of this project are to: 1. Design and synthesize chemical probes to study the role of fucose-galactose in the brain 2. Apply the chemical probes, in conjunction with advance mass spectrometry methods, to identify (a) fucose-galactose binding proteins (i.e. lectins) and (b) fucose-galactose glycoproteins 3. Use co-immunoprecipitation and fluorescence microscopy studies to investigate pairwise interactions between the lectins and glycoproteins identified in the previous section 4. Study the role of fucose-galactose saccharides in regulating the morphology and function of nerve cells ? ? The long-term goal of this program is to provide a better understanding of the molecular and cellular underpinnings of learning and memory. Because the program takes a distinctly chemical approach, these studies may ultimately reveal novel points of therapeutic intervention and enable the design of molecules capable of modulating cognition and improving deficits associated with age and neurodegenerative disease.
