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

小行星9600963 嵌入神经细胞膜的特定分子（分子受体）如何介导神经系统的信号传导的细节仍然没有完全理解。 一种特殊的分子，烟碱乙酰胆碱受体介导骨骼肌、自主神经系统和大脑许多区域的神经传递。 已知在大脑中存在许多不同的烟碱乙酰胆碱受体亚型，但它们的功能仍然难以捉摸，因为亚型特异性探针不可用。 该研究项目的目标是分离出人工的、亚型特异性的肽毒素，这些肽毒素可用于研究不同烟碱乙酰胆碱受体亚型的功能。这些肽将使用噬菌体展示技术从随机肽文库中选择。 这种新技术允许同时选择展示在噬菌体颗粒表面上的肽，这些噬菌体颗粒也包含编码肽序列的DNA。 将选择噬菌体上展示的肽与烟碱受体亚型特异性序列结合。 此外，这笔赠款有助于支持分子神经生物学的新实验室课程。 这项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。 根据这项赠款开发的实验室课程有望提供一种新的分子神经生物学教学方法。

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.