CAREER: Novel Subtype-Specific Peptide Ligands of the Nicotinic Acetylcholine Receptor from Phage Display Libraries

9600963麦克莱恩关于神经细胞膜(分子受体)中的特定分子如何调节神经系统的信号传递的细节仍不完全清楚。烟碱型乙酰胆碱受体是一种特殊的分子，它在骨骼肌、自主神经系统和大脑的许多区域介导神经传递。众所周知，大脑中有许多不同的烟碱型乙酰胆碱受体亚型，但由于没有亚型特异性探针，它们的功能仍然难以捉摸。这项由这笔赠款资助的研究项目的目标是分离出可用于研究不同烟碱型乙酰胆碱受体亚型功能的人工亚型特异性多肽毒素。这些多肽将通过噬菌体展示技术从随机多肽库中挑选出来。这项新技术允许同时选择展示在噬菌体颗粒表面的多肽，这些噬菌体颗粒也包含编码多肽序列的DNA。展示在噬菌体上的多肽将被选择与烟碱受体亚型特定序列结合。此外，这笔赠款还帮助资助了一门新的分子神经生物学实验室课程。这项由这笔赠款资助的研究有望为神经元的分子功能提供重要的见解，并为进一步研究神经元受体的分子生物学提供新的工具。根据这笔赠款开发的实验室课程有望为分子神经生物学的教学提供一种新的方法。

9600963 McLane The details of how specific molecules imbedded in nerve cell membranes (molecular receptors) mediate the signaling of nervous systems are still not fully understood. One particular molecule, the nicotinic acetylcholine receptor mediates neurotransmission in skeletal muscle, in the autonomic nervous system, and in many areas of the brain. It is known that there are many different nicotinic acetylcholine receptor subtypes in the brain, but their function remains elusive because subtype-specific probes are not available. The goal of the research project funded by this grant is to isolate artificial, subtype-specific peptide toxins that can be used to study the function of different nicotinic acetylcholine receptor subtypes. These peptides will be selected from random peptide libraries using phage display technology. This new technology allows the simultaneous selection of peptides that are displayed on the surface of bacteriophage particles, which also contain the DNA encoding the peptide sequence. Peptides displayed on phage will be selected for binding to nicotinic receptor subtype-specific sequences. In addition, this grant helps support a new laboratory course in molecular neurobiology. The research funded by this grant is expected to provide important insights into the molecular function of neurons and to lead to new tools for further research into the molecular biology of neuronal receptors. The laboratory course to be developed under this grant is expected to provide a novel approach to teaching molecular neurobiology.