College of Medicine
Department of Neuroscience
- Molecular neurobiology
- Regulation of genes encoding neuronal nicotinic acetylcholine receptors
- Characterization of nicotinic receptors on adrenal chromaffin cells
Neuronal nAChRs are pentameric membrane proteins which function as ligand-gated ion channels and are composed of multiple a and ß subunits. Neuronal nAChR a genes encode the ligand binding subunit while the ß genes encode structural subunits. Eight neuronal nAChR a subunit genes (a2-a9) and three nAChR ß subunit genes (ß2-ß4) have been identified. Different combinations of and subunits produce nAChR subtypes with different pharmacological and ion conducting properties. Ongoing work is in three areas:
- Studies on transcriptional regulation of the a3 and a7 neuronal nAChR genes. Dr. Boyd's lab is identifying transcriptional control elements responsible for expression of these nAChR subunit genes in neurons and characterizing transcription factors binding to the nAChR subunit promoters. Dr. Boyd's lab is also examining the mechanisms controlling expression of these genes during differentiation and changes in membrane potential.
- Characterization of nAChRs expressed on adrenal chromaffin cells. In collaboration with Dr. Dennis McKay in the College of Pharmacy, they are identifying nAChR subtypes present on bovine adrenal chromaffin cells. Dr. Boyd's team has found that at least two nAChR subtypes are responsible for mediating catecholamine release from chromaffin cells. They are now determining the subunit composition of these subtypes and how the expression and turnover of these nAChRs are controlled.
- Identification of zebrafish neuronal nAChR genes. Zebrafish provide an excellent model for studying the effects of genetic mutations on nervous system development, especially at early times when mouse embryos in utero are inaccessible. Zebrafish also have potential as a system to study mechanisms underlying tolerance, sensitization and addiction to nicotine, a potent drug of abuse. The actions of nicotine are mediated by neuronal nAChRs. While a neuromuscular nAChR has been identified in zebrafish, nothing is known about zebrafish neuronal type nAChRs. Researchers are cloning zebrafish neuronal nAChRs and determining the expression pattern of zebrafish neuronal nAChR genes during development. The information derived from these studies will be used to develop zebrafish as a model for studying the role of nAChRs in development of the nervous system and the actions of nicotine on the vertebrate nervous system.
Research Techniques: Students in Dr. Boyd's laboratory learn and use these techniques in their research studies:Molecular: PCR, Northern and Southern blotting, genomic and cDNA cloning, DNA sequencing, DNAse I footprinting, gel-shift analysis of DNA-protein interactions and transinfection
Postdoctoral: University of California, San Diego, Dr. Darwin Berg