// YOUSRA EL GHALEB 
Flucher Research Group
Institute of Physiology,
Medical University of Innsbruck
// INFORMATION
Nationality: Dutch
Education: MSc in Molecular Neuroscience at the University of Amsterdam
E-Mail: yousra.el-ghaleb@i-med.ac.at
ORCID
Supervisor: Univ.-Prof. Dr. Bernhard Flucher
// PROJECT
In my research I focus on Cav1.1 and Cav3.3, the first and the last member of the family of ten different voltage gated calcium channels. In line with studying the two extremes of the calcium channel family, I also work with two extremes when it comes to the approach we use.
In order to elucidate the mechanisms of calcium channel voltage gating, I use on one hand a bottom-up approach starting with putative molecular interactions in Cav1.1 identified by our structure modeler Monica Fernández-Quintero. I then use site-directed mutagenesis and electrophysiology to study the potential role of these interactions in the regulation of voltage sensing and/or gating kinetics.
On the other hand, I use a top-down approach for my Cav3.3 studies. Here the starting point is putative disease mutations identified in patients with neurodevelopmental disorders and epilepsy. Again, I use site-directed mutagenesis and electrophysiology to research the effect of these mutations on channel gating and in order to understand, on biophysical level, how these mutations result in the phenotype observed in the patients of our collaborators. Additionally, we go all the way back down from phenotype to channel structure in order to explain the effects we see on a biophysical level by studying the change in molecular interactions caused by the mutation.
In this way we learn more and more about how specific interactions in voltage gated calcium channels differently orchestrate the complex mechanisms of channel opening and closing, and how changes on the atomic level can lead to dramatic changes in channel gating and sever disease in patients.
Methods: whole-cell patch-clamp, skeletal muscle cell culture and transfection, mutagenesis
// PUBLICATIONS
El Ghaleb Y, Campiglio M, Flucher BE (2019) Correcting the R165K substitution in the first voltage-sensor of CaV1.1 right-shifts the voltage-dependence of skeletal muscle calcium channel activation. Channels (Austin) 13(1):62–71.
// INTERNAL COLLABORATIONS
// EXTERNAL COLLABORATIONS
Prof. Kerstin Kutsche at the Institute of Human Genetics of the University Medical Center Hamburg-Eppendorf