STUDY OF GROWTH-ASSOCIATED PROTEINS

THE OBJECTIVE OF THIS PROJECT IS TO EXAMINE THE MOLECULAR CHANGES THAT UNDERLIE SPINAL CORD REGENERATION IN THE LAMPREY. WE WILL IDENTIFY AND ISOLATE NOVEL GROWTH-ASSOCIATED PROTEINS (GAPS) DERIVED FROM THE CENTRAL NERVOUS SYSTEM THAT ARE EXPRESSED DURING THE COURSE OF NORMAL DEVELOPMENT AND SUBSEQUENT TO CNS INJURY. IN HIGHER VERTEBRATES, GAPS ARE KNOWN TO BE EXPRESSED IN GREATER THAN NORMAL QUANTITIES DURING PERIODS OF AXONAL OUTGROWTH AND IN RESPONSE TO INJURY. THE SEARCH FOR GAPS DERIVED FROM THE CNS OF THE SEA LAMPREY REPRESENTS A POTENTIALLY VALUABLE AVENUE OF RESEARCH AS LAMPREYS ARE THE ONLY VERTEBRATES TO DEMONSTRATE FUNCTIONAL RECOVERY FOLLOWING COMPLETE SPINAL CORD TRANSECTION. THEREFORE, THE GAPS EXPRESSED IN THIS SPECIES COULD PROVIDE UNIQUE TOOLS FOR THE INVESTIGATION OF THE MECHANISMS OF BOTH NORMAL AXONAL OUTGROWTH AND NERVE REGENERATION. DURING PHASE I WE WILL DEVELOP A NOVEL IN VITRO ISOLATED NEURAXIS PREPARATION THAT TAKES ADVANTAGE OF THE UNIQUE FEATURES OF LAMPREY CNS PHYSIOLOGY. THIS PREPARATION WILL BE USED IN CONJUNCTION WITH TWO-DIMENSION (2-D) GEL ELECTROPHORESIS OF RADIOLABELED PROTEINS, AS IT HAS BEEN EMPLOYED SUCCESSFULLY IN THE PAST IN THE IDENTIFICATION AND ISOLATION OF GAPS FOUND IN MANY OTHER VERTEBRATE SPECIES.