9728147 TIGYI The goal of this research is to understand the fundamental mechanisms that regulate the development of neuronal connections in the brain. Past research by this group has led to the discovery of a novel group of molecules (lysophosphatidates) that inhibit the outgrowth of the neuronal processes that provide the wiring of the nervous system. Interestingly, these molecules are generated after injury to the central nervous system and might impair regeneration and recovery of function. Dr. Tigyi and his collaborators will investigate the molecular signals that mediate this inhibitory effect. Specifically, they will generate, using molecular biological techniques, special cell lines that are deficient in one of three key molecular switches, Cdc42, Rac, and Rho, which are presumed to be involved in the inhibitory effect. They will then analyze the molecular mechanism that turns these switches on and off. By using these engineered neuron-like cells, they will be able to answer which one or more of these three switches needs to be turned on for the inhibition to take place. Once the switches mediating the inhibitory effect are determined in the cell culture system, it will be possible in future research to investigate the specific role of lysophosphatidates and the switches they control in the development, regeneration, and repair of the nervous system.
