Research mission

The laboratory for molecular biophysics, physiology and pharmacology studies the underlying mechanisms of the excitability of the heart or nervous system. The electrical activity is regulated by ionic currents passing the plasmamembrane, originating from the opening and closing of ion channels. The determination of the molecular architecture, the modulation by external factors or drugs, the elucidation of the structure function relationship as well as defects of ion channel activity causing congenital diseases are the main research topics of the laboratory. More specifically the following research topics are currently under investigation: - Molecular architecture of ion channel subunits in vivo. Specifically the role of the novel subunits Kv6.3, Kv10.1, Kv11.1 and KChIP1b are investigated. - The structure function relationship is investigated in Kv channels. The localization of the intracellular gate and the coupling to voltage sensing is determined. - Study of mutations that are associated with congenital long QT. At present this is focused on hERG and KCNQ1/KCNE1. Through collaboration also mutations involved in epilepsy (KCNQ2/KCNQ3) and deafness (KCNQ1/KCNE1) are investigated. - The electrical remodeling is studied in atrial fibrillation. - Effects of drugs on ion channel function. Methods: Molecular Biology: - Creating point mutaions and/or chimeric channels by PCR - Cloning of channels and/or ß-subunits - Screening for interacting subunits by protein-protein interaction assays - Demonstrating interactions with standard molecular biology techniques such as co-immuno precipitation - Construction of fusion proteins of channels and fluoresent markers - Cell culture and creating stable cell lines - Micro array experiments to determine in vivo expression - RNAi experiments to eliminate native expression - Creating contructs for transgenic animals Electrophysiology: - Transient expression of ion channels in different cell lines (HEK293, LTK-,CHO and COS) - Whole-cell and single-channel measurements with patch clamp - Determination of Kd and kinetics of interaction between drugs and ion channels In association with other labs: - Confocal microscopy for trafficking of ion channels in real time - FRET technique for in vivo interactions - EPR spectroscopy for structural clarification