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

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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.