Department of Psychology
Department of Psychology

Dr. Marcel Goldschen-Ohm, "Ion Channel Ligand Association Mechanisms Using Single-Molecule Spectroscopy”

Wed, February 22, 2017 | NHB 1.720

10:00 AM

Department of Neuroscience
Faculty Recruitment Seminar


Marcel Goldschen-Ohm, Ph.D.
University of Wisconsin-Madison
Department of Neuroscience
Baron Chanda Laboratory



“Ion Channel Ligand Association Mechanisms Using Single-Molecule Spectroscopy”



Wednesday, February 22nd
11 am - NHB 1.720


A chalk-talk will follow on Thursday, Feb 23rd at 10 am in NHB 3.202


Abstract: Molecular recognition is a cornerstone of cellular signaling processes. However, most observations of binding rely on ensemble measurements that average over and thereby obscure the individual underlying steps. Single-molecule fluorescence can reveal these dynamic events, but is traditionally limited to low concentrations of fluorophores only suitable for studying high affinity reactions. Here, we show how a combination of fluorescence resonance energy transfer (FRET) and zero-mode waveguide nanophotonic devices can be used to study single-molecule association dynamics at the micromolar to millimolar concentrations necessary for many relevant signaling pathways. As an exemplar system, we apply this approach to cyclic nucleotide binding at its receptor domain from hyperpolarization cyclic nucleotide-gated (HCN) ion channels. Our observations reveal the underlying dynamic events during cyclic nucleotide binding: an initial encounter complex when the binding site is in its receptive state, followed by an isomerization of the bound complex that traps the ligand in the binding site.

My background includes electrophysiology and spectroscopy at both single-molecule and macroscopic levels, and kinetic modeling of ion channel function. I plan to combine these approaches to study dynamic events underlying allosteric channel behavior that are difficult to observe with structural or bulk averaged methods.

 

Sponsored by: Department of Neuroscience

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