Scripps Research Joint Appointments

Department of Neuroscience
Kellogg School of Science and Technology
Faculty, Kellogg School of Science and Technology

Research Focus

Membrane proteins, and ion channels in particular, are important molecular switches that control nerve cell activity in the brain.  Ion channels are drug targets for the treatment of brain afflictions including addiction, pain, depression, and loss of consciousness. My lab employs membrane protein crystallography, electrophysiology, and pharmacology to understand ion channel activation and develop receptor-selective compounds for the treatment of neurological disease.

My research is uniquely situated at the interface of ion channel regulation and lipid signaling. Recent findings, including my own, suggest that lipids bind to and modulate ion channels by chemical means analogous to classical agonists or neurotransmitters. The number of ion channels inhibited or activated by lipids is extensive; they include the K_ir, K_v, hERG, Slo, K₂P, CNG, ENaC, TRP, P₂X, nAChR, and GABA channels. We are developing the tools to answer important biophysical questions about lipid regulation of ion channels.

Individuals, who are interested in joining the lab, please email Scott Hansen. Postdoc applicants with experience in protein biochemistry, enzymology, electrophysiology, or pharmacology are particularly encouraged to apply. 

Professional Experience

Ph.D. University of California, San Diego 2005

Awards & Professional Activities

Postdoctoral Fellowship (2007-2011) Howard Hughes Medical Institute
Martin D. Kamen Award (2006), best doctoral thesis; University of California, San Diego
Young Scientist Travel Award (2006) American Society of Pharmacology and Experimental Therapeutics
Dissertation Fellowship (2003-2005) Tobacco Related Disease Research Program

Selected References

Hansen SB, Xiao Tao, Roderick MacKinnon “Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2” Nature 2011, 477:495-98

Hansen SB, Wang, HL, Taylor P, and Sine SM “An Ion-Selectivity Filter in the Extracellular Domain of Cys-loop Receptors Reveals Determinants for Ion Conductance. J Biol Chem. 2008 Dec 26:283(52):36066-70

Hansen SB and Taylor P “Galanthamine and Non-competitive Inhibitor Binding to ACh-binding Protein: Evidence for a Binding Site on Non-a-subunit Interfaces of Heteromeric Neuronal Nicotinic Receptors” J. Mol. Biol. 2007 June 369, 895-901 

Gao F, Mer G, Tonelli M, Hansen SB, Burghart TP, Taylor P, Sine SM. “Solution NMR of Acetycholine Binding Protein Reveals ACh-mediated Conformational Change of the C-loop” Mol Pharmacol. 2006 Oct 70(4): 1230-5

Bourne Y, Talley TT, Hansen SB, Taylor P and Marchot P “Crystal structure of a Cbtx-AChBP complex reveals essential interaction between snake a-neurotoxins and nicotinic receptors” Embo J 2005, 24: 1512-22

Hibbs RE, Johnson DA, Shi J, Hansen SB, and Taylor P “Structural Dynamics of the a-Neurotoxin-Acetylcholine Binding Protein Complex: Hydrodynamic and Fluorescence Anisotropy Decay Analyses” Biochemistry 2005, 44:16602-11

Hansen SB, Sulzenbacher G, Huxford T, Marchot P, Taylor P, and Bourne Y “Structures of Aplysia AChBP complexes with agonists and antagonists reveal distinctive binding interfaces and conformations” Embo J 2005, 24:3635-46

Gao F, Bren N, Burghardt TP, Hansen SB, Henchman RH, Taylor P, McCammon JA, Sine SM. “Agonist-mediated conformational changes in acetylcholine-binding protein revealed by simulation and intrinsic tryptophan fluorescence” J Biol Chem. 2005 Mar 4;280(9):8443-51

Bouzat C, Gumilar F, Spitzmaul G, Wang HL, Rayes D, Hansen SB, Taylor P, and Sine SM “Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel” Nature 2004 Aug 19:430:896-900

Hansen SB, Talley TT, Radic Z, and Taylor P. “Structural and ligand recognition characteristics of an acetylcholine binding protein from Aplysia californica” J Biol Chem. 2004 Jun 4:279(23):24197-202

Gao F, Bern N, Little A, Wang HL, Hansen SB, Talley TT, Taylor P, and Sine SM. “Curariform antagonists bind in different orientations to acetylcholine-binding protein” J Biol Chem. 2003 Jun 20;278(25):23020-6.

Hansen SB, Radic Z, Talley TT, Molles BE, Deerinck T, Tsigelny I, and Taylor P. “Tryptophan fluorescence reveals conformational changes in the acetylcholine binding protein” J Biol Chem. 2002 Nov 1;277(44):41299-302.

Issued Patents

Hansen SB, Radic Z, and Taylor P “Methods for identifying agents that modulate LGIC receptor activity.” United States Patent 7947466. 24 May 2011

Links

Neuroscience page

Press release, Appointment

Faculty of 1000

Webvision: notable paper