Functional and structural characterization of small molecule interactions with ion channels

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Goal of this research project is to rationally design small molecules that interact with ion channels and investigate their mechanism of action in detail. For this purpose, a variety of biophysical methods including electrophysiology and solid-state nuclear magnetic resonance (ssNMR) spectroscopy shall be combined to study the action of synthetically designed channel ligands at a structural and functional level. Structural analysis will be based on multidimensional ssNMR experiments with potassium channel - small molecule complexes in a lipid bilayer environment. The spectroscopic results will be complemented with both biochemical binding experiments and electrophysiological recordings including mammalian voltage-gated potassium channels of therapeutic interest. Combination of these experiments with synthetic organic chemistry will enable the design of novel pharmacological compounds relevant for the treatment of a variety of human diseases and should lead to novel molecular tools for modulating electrical properties of neurons.