Forschungsprofil Dr. Misha Kudryashev

Dr. Misha Kudryashev
  • Since Nov 2015 Group Leader at MPI for Biophysics and BMLS, Goethe University of Frankfurt.
    Sofja Kovalevskaja Award – funded group (from the Humboldt Foundation)
    Associated member of SFB807 (www.sfb807.de)  and Cluster of Excellence on Macromolecular Complexes (www.cef-mc.de)
  • 2009-2015 Postdoc with Henning Stahlberg and Marek Basler at Biozentrum, University of Basel, Switzerland
  • 2005-2009 PhD with Freddy Frischknecht at University of Heidelberg, Germany
  • 2000-2005 Diploma in Physics from Krasnoyarsk State University, Russia

Native structure and gating of ion channels

Recent developments in cryo electron microscopy allow approaching problems that was difficult to solve with the other structural biology methods. In particular, it is now possible to understand structure of non-crystalline ion channels in atomic details at a resolution of 3-4 angstrom (http://www.ncbi.nlm.nih.gov/pubmed/25910205). This allows 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 like depression and schizophrenia. We use single particle cryo-EM to gain insights into gating and regulation of these important molecules.

Even more exciting, now it is possible to study structure of membrane proteins at high resolution in membranes which Is critical for maintaining native conformations and functionality. For this we use sub-tomogam averaging from cryo electron tomograms (http://www.ncbi.nlm.nih.gov/pubmed/26724993, the image is adapted from this article), this allows observing 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



Selected Publications on structure of large macromolecular complexes:

Nans A*, Kudryashev M*, Saibil HR, Hayward RD. Structure of a bacterial type III secretion system in contact with a host membrane in situ. Nat Commun. 2015 Dec 11;6:10114

Kudryashev M
, Wang R, Brackmann M, Scherer S, Maier T, Baker D, DiMaio F, Stahlberg H, Egelman EH, Basler M, The structure of the type six secretion system contractile sheath solved by cryo-electron microscopy, Cell 160 (5), 952-962

Kudryashev M*, Stenta M*, Schmelz S*, Amstutz M*, Wiesand U*, Castaño-Díez D, Degiacomi M, Münnich S, Bleck CKE, Kowal J, Diepold A, Heinz DW, Dal Peraro M, Cornelis GR, Stahlberg H, In situ Structural Analysis of the Yersinia enterocolitica. Injectisome, Elife. 2013 Jul 30;2:e00792.

Dudkina NV, Kudryashev M, Stahlberg H, Boekema EJ, Interaction of complexes I, III, and IV within the bovine respirasome by single particle cryoelectron tomography, PNAS. 2011 Sep 13;108(37):15196-200, .

Kudryashev M#, Cyrklaff M, Wallich R, Baumeister W, Frischknecht F#. Distinct in situ structures of the Borrelia flagellar motor, J Struct Biol. 2010 Jan;169(1):54-61

 

Selected publications on method development:

Kudryashev M#, Castaño-Díez D, Deluz C, Hassaine G, Grasso L, Graf-Meyer A, Vogel H#, Stahlberg H. The Structure of the Mouse Serotonin 5-HT3 Receptor in Lipid Vesicles. Structure 2015 24(1): 165–170

Wang R, Kudryashev M, Li X, Egelman EH, Basler M, Cheng Y, Baker D, DiMaio F, Accurate de novo protein structure determination from near-atomic resolution cryo-EM maps, Nature methods, 2015 12 (4), 335-338

Castano-Diez D, Kudryashev M, Arheit M, Stahlberg H, Dynamo: A flexible, user-friendly development tool for subtomogram averaging of cryo-EM data in High Performance Computing environments, J Struct Biol. 2012, May;178(2):139-51.

Kudryashev M, Stahlberg H, Castaño-Díez D, Assessing the benefits of focal pair cryo-electron tomography, J Struct Biol. 2012 May;178(2):88-97.

* equal contribution
# corresponding author

Kontaktinformationen:

Max-Planck-Institut für Biophysik

Dr. Misha Kudryashev
Sofja Kovalevskaja Gruppe

Tel.: +49 (0) 69 6303 1700
Fax: +49 (0) 69 6303 3002

E-Mail:misha.kudryashev(at)biophys.mpg.de

October 2016; Simon, Misha, Eva, Daniel (alumni), Patricia, Ariane, Yingyi, Luise, Wenbo and Ricardo

Gruppenmitglieder:

Group Leader:

Postdoctoral Researchers:

  • Dr. Eva Cunha
  • Dr. Patricia Dijkman

Ph.D. Students:

  • Wenbo Chen
  • Ricardo Sanchez
  • Yingyi Zhang

Research assistant:

  • Luise Eckhardt-Strelau

Master Students:

  • Robert Gebauer
  • Ariane Sahebzade
  • Simon Wiessing

Group Alumni:

  • Daniel Schröder
    project student Sept. 2016 - March 2017,
    moved to EMBL Heidelberg for a Master Project