Misha Kudryashev: Native Structure and Gating of Ion Channels
Guest Group – from August 2021 Misha Kudryashev moved to the Max Delbrück Center for Molecular Medicine in Berlin, Germany
In situ structural biology of membrane protein complexes
Our research aims at understanding structure and regulation of medically important membrane proteins mostly from excitable cells. We are particularly interested in the effects that lipids, transmembrane gradients and native interacting partners have on activation of ion channels. To experimentally determine the defined conformations of ion channels in my group we use membrane protein biochemistry, biophysics, cryo electron microscopy (cryo-EM) and tomography (cryo-ET) as well as computer science.
We use two structural methods as main tools: firstly, single particle cryo-EM to understand protein structure at near-atomic resolution in presence of lipids in the defined functional states (open, closed, deactivated). Secondly, in situ structural biology by cryo electron tomography and subtomogram averaging (StA), which enables structural analysis in native or native-like environment. While a few high-resolution structures have already been reported, the method is currently cumbersome and mostly results in structures with lower resolution. In order to turn subtomogram averaging into a broadly used structural biology technique we develop algorithmic tools and transparent software workflows providing significant boost in resolution.
We are primarily funded by the amazing Sofja Kovalevskaja Award from the Alexander von Humboldt Foundation. We further thank German Research Foundation (DFG) for a generous project grant. Fellowship programmes from: Chinese Student Council, Taiwaneese Government, Josef Buchmann Foundation, Max Planck International Graduate School (IMPRS), G-Max Precision. The group received funding from the state of Hesse two large research consortia: Collaborative Research Project on Membrane Transport (http://www.sfb807.de/) and Cluster of Excellence on Macromolecular Complexes (https://www.cef-mc.de/), both funded by DFG.
We are a multinational multidisciplinary group working together to solve challenging basic problems related to membrane proteins. If you are interested to join us on a relatively long-term basis please write an email to misha.kudryashev(at)biophys.mpg.de and with a CV and a few words about your interests.