Comprehensive study of the function and interrelationships of the proteins controlling the metabolism of the neurotransmitter GABA is important not only for understanding the basic biology of neuronal signaling, but also for uncovering potential new therapies for many severe neurological disorders. Such study has been hampered by the current lack of specific research reagents targeting such molecules, in particular monoclonal antibodies that recognize key enzymes controlling the synthesis, delivery, and disposition of GABA. To address these needs, we intend to generate such antibodies and optimize their use in critical laboratory manipulations. These goals will be met through a program of antigen production, immunization, hybridoma fusion and antibody screening, and rigorous testing of generated antibodies in multiple laboratory techniques. The antibodies produced in this proposal, and in a follow-on phase II proposal, will serve the research community as available laboratory reagents to study basic biology, but will also contribute to novel therapy development in two ways: first, directly through their potential use as novel therapeutic agents, and second, through the new discoveries their laboratory use will allow.
