Ion channel structural biology - from basic to applied sciences

Ion channels are essential for cellular life and imperative for basic and applied biomedical research. Despite their significance many ion channel classes remain elusive at the molecular level.

The overarching goal of this cutting-edge research program is to elucidate the molecular principles and determinants of human ion channel conductance, and how flux can be modulated through interference with ligands, which is critical for health and represent highly attractive targets in the treatment of disease.

The focus will be on three separate ion channel families, voltage-gated KCNQ potassium channels, magnesium Mrs2 channels and optogenetic non-specific channelrhodopsins.

To accomplish this ambitious goal, a multidisciplinary strategy is proposed involving a complementary set of biochemical, biophysical and structural biology techniques centered on single particle Cryo Electron Microscopy (cryo-EM), thereby revealing imperative aspects of the mechanism and regulation that could not be obtained with either approach separately.

The five-year program extends naturally from recent breakthroughs of the proposer and is based on promising preliminary results, including multiple complementary membrane protein structures. Positive results will significantly move the frontiers within this rapidly developing field.

Furthermore, a framework will be provided for downstream in-depth studies and for attenuation efforts of ion channels, with potential therapeutic interest.