Monoclonal Antibodies to GABA Metabolic Pathway Proteins

描述（由申请人提供）：控制神经递质GABA代谢的蛋白质的功能和相互关系的综合研究不仅对于理解神经元信号传导的基础生物学很重要，而且对于发现许多严重神经系统疾病的潜在新疗法也很重要。目前缺乏靶向这些分子的特异性研究试剂，特别是识别控制GABA合成、递送和处置的关键酶的单克隆抗体，阻碍了这种研究。为了满足这些需求，我们打算产生这样的抗体，并优化它们在关键实验室操作中的使用。这些目标将通过抗原生产、免疫接种、杂交瘤融合和抗体筛选程序以及在多种实验室技术中对生成的抗体进行严格测试来实现。在该提案中产生的抗体，以及在后续的第二阶段提案中，将作为研究社区的可用实验室试剂来研究基础生物学，但也将以两种方式促进新疗法的开发：第一，直接通过其作为新型治疗剂的潜在用途，第二，通过其实验室用途将允许的新发现。

DESCRIPTION (provided by applicant): 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.