Nicotinic acetylcholine receptors (nAChRs) are neurotransmitter-gated ion channels that are implicated in neurological and psychiatric disorders such as Alzheimer’s disease and schizophrenia. A current focus of the Millar lab (UCL) is to use molecular and electrophysiological techniques to examine the pharmacological diversity of this important receptor family. In recent years, much of the work in the lab has had a ‘drug discovery’ focus and has involved collaborations with UCL-based synthetic chemists and also industrial collaborations. In addition, this PhD project will also provide an opportunity (through interaction with the Wallace lab at Birkbeck) to develop computer-based models of drug-receptor interactions.
Gill, J.K., Savolainen, M., Young, G.T., Zwart, R., Sher, E. and Millar, N.S. (2011) Agonist activation of α7 nicotinic acetylcholine receptors via an allosteric transmembrane site. Proceedings of the National Academy of Sciences USA 108, 5867-5872.
Pa?czy?ska, M.M., Jindrichova, M., Gibb, A.J. and Millar, N.S. (2012) Activation of α7 nicotinic receptors by orthosteric and allosteric agonists: influence on single-channel kinetics and conductance. Molecular Pharmacology 82, 910-917.
Gill, J.K., Dhankher, P., Sheppard, T.D., Sher, E. and Millar, N.S. (2012) A series of α7 nicotinic allosteric modulators with close chemical similarity but diverse pharmacological properties. Molecular Pharmacology 81, 710-718.
Ulmschneider, M.B., Bagnéris, C., McCusker, E.C., DeCaen, P.G., Delling, M., Clapham, D.E., Ulmschneider, J.P. and Wallace, B.A. (2013) Molecular dynamics of ion transport through the open conformation of a bacterial voltage-gated sodium channel. Proc. Nat. Acad. Sci. USA 110, 6364-6369.
Bagnéris, C., DeCaen, P.G., Hall, B.A., Naylor, C.E., Clapham, D.E., Kay, C.W.M., Wallace, B.A. (2013) Role of the C-terminal domain in the structure and function of tetrameric sodium channels, Nature Communications 4:2645.