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Professor of Biology

Office: 133 Stanley
Phone: (765) 983-1464
Fax: (765) 983-1497
E-Mail: rosenbo@earlham.edu

Ph.D., Physiology, Yale University
A.B., Physics, Oberlin College

Research Interests: Molecular mechanisms of activation of ion channels

Our research is focused on the molecular mechanisms of activation of neuronal nicotinic acetylcholine receptors. These receptors mediate cholinergic neurotransmission and are essential for normal synaptic activity in the brain. They are the target for nicotine, so they are an important component in nicotine addiction. Abnormalities of cholinergic neurotransmission are important in Alzheimer’s disease, schizophrenia, epilepsy, and other neurological disorders.

We are testing the hypothesis that acetylcholine-driven conformational changes of the receptors that occur during receptor activation include subunit rotation and intrasubunit movements of a specific beta-sheet.  To characterize these conformational changes, we use cysteine mutagenesis, analysis of chemical modification rates, and electrophysiological approaches to characterize the functional properties of cloned receptors. We use a molecular model of the ligand-binding domain of the receptors to guide our mutagenesis and to help us interpret the results.

Courses

• Cells, Genes, and Inheritance (CGI)
• Cell Physiology
• Anatomy and Physiology: Excitable Cells
• Anatomy and Physiology: Metabolism and Endocrinology

Other Activities and Interests: Learning Spanish and flying

Links: Curriculum vita and NIH Biosketch

Recent and selected earlier publications

• Barron SC, McLaughlin JT, See JA, Richards VL, Rosenberg RL (2009) An allosteric modulator of alpha7 nicotinic receptors, N-(5-Chloro-2,4-dimethoxyphenyl)-N'-(5-methyl-3-isoxazolyl)-urea (PNU-120596), causes conformational changes in the extracellular ligand binding domain similar to those caused by acetylcholine.Molecular Pharmacology 76: 253-263. abstract
• McLaughlin JT, Barron SC, See JA, Rosenberg RL (2009) Conformational changes in alpha 7 acetylcholine receptors underlying allosteric modulation by divalent cations. BMC Pharmacology 9: 1-10. abstract
• McLaughlin JT, Fu J, Rosenberg RL (2007) Agonist-driven conformational changes in the inner beta-sheet of alpha7 nicotinic receptors. Molecular Pharmacology 71: 1312-1318. abstract
• Olesky M, Zhao S, Rosenberg RL, Nicholas RA (2006) Porin-mediated antibiotic resistance in Neisseria gonorrhoeae: ion, solute, and antibiotic permeation through PIB proteins with penB mutations. Journal of Bacteriology188: 2300-2308. abstract
• McLaughlin JT, Fu J, Sproul AD, Rosenberg RL (2006) Role of the outer beta-sheet in divalent cation modulation of alpha7 nicotinic receptors. Molecular Pharmacology. 70: 16-22. abstract
• Lyford LK, Sproul AD, Eddins D, McLaughlin JT, Rosenberg RL (2003) Agonist-induced conformational changes in the extracellular domain of alpha 7 nicotinic acetylcholine receptors. Molecular Pharmacology. 64: 650-658. abstract
• Lyford LK, Rosenberg RL (1999) Cell-free expression and functional reconstitution of homo-oligomeric alpha7 nicotinic acetylcholine receptors into planar lipid bilayers. Journal of Biological Chemistry 274: 25675-25681. abstract
• Koplas PA, Rosenberg RL, Oxford GS. (1997) The role of calcium in the desensitization of capsaicin responses in rat dorsal root ganglion neurons. Journal of Neuroscience 17: 3525-3537. abstract
• Desai SA, Rosenberg RL (1997) Pore size of the malaria parasite's nutrient channel. Proceedings of the National Academy of Sciences USA. 94: 2045-2049. abstract
• Rosenberg RL, East JE (1992) Cell-free expression of functional Shaker potassium channels. Nature 360: 166-169. abstract