Dr. Misha Kudryashev
Independent Research Group (Sofia Kovaleskaja)
Native structure and gating of ion channels
Recent developments in cryo electron microscopy allow approaching problems that have been difficult or impossible to solve with the other structural biology methods. In particular, it is now possible to understand the structure of non-crystalline ion channels in atomic detail at a near-atomic resolution of 3-4 Angstrom (http://www.ncbi.nlm.nih.gov/pubmed/25910205).
This allows for a mechanistic understanding of gating and opens eventual opportunities for rational drug design. Our lab targets complex ion channels in the human brain implicated in numerous neurodegenerative diseases such as depression and schizophrenia. We use single particle cryo-EM to gain insights into gating and regulation of these important molecules. High-resolution single particle cryo electron microscopy, also known as “cool microscope technology which revolutionised biochemistry” was recognised by a Noble Prize in Chemistry to Jacques Dubochet, Joachim Frank and Richard Henderson in 2017 (https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2017/press.html)
Even more exciting, it is now possible to study the structure of membrane proteins at high resolution directly within membranes, which is critical for maintaining native conformations and functionality. For this we use subtomogram averaging from cryo electron tomograms (http://www.ncbi.nlm.nih.gov/pubmed/26724993, the image is adapted from this article), this allows to observe ion channels at a resolution of secondary structure and may be combined with induction of the defined functional states. This “in situ” structural biology approach still requires developments in hardware and software. In our group we develop algorithms for subtomogram averaging at higher resolution using the entire range of modern tools. The developments are based on our Matlab-based package Dynamo (https://wiki.dynamo.biozentrum.unibas.ch/w/index.php/Main_Page), and are actively shared with the EM community.
For informal job inquires at bachelor-master-predoc-postdoc levels and other questions please write me to misha.kudryashev(at)biophys.mpg.de