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

Publications
(* equal contribution, # corresponding author)

Devos S, Van Putte W, Vitse J, Van Driessche G, Stremersch S, Van Den Broek W, Raemdonck K, Braeckmans K, Stahlberg H, Kudryashev M, Savvides SN, Devreese B, Membrane vesicle secretion and prophage induction in multidrug-resistant Stenotrophomonas maltophilia in response to ciprofloxacin stress, Environ Microbiol. 2017 May 10, doi: 10.1111/1462-2920.13793

Castaño-Díez D, Kudryashev M, Stahlberg H. Dynamo Catalogue: Geometrical tools and data management for particle picking in subtomogram averaging of cryo-electron tomograms., J Struct Biol. 2016 Jun 8. pii: S1047-8477(16)30111-3

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. 2016 Jan 5;24(1):165-70

Nans A*, Kudryashev M*, Saibil HR, Hayward RD. Structure of a bacterial type III secretion system in contact with a host membrane in situ. Nature Communications. 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. 2015 Feb 26;160(5):952-62

  • Highlighted in: Nunes-Alves C, Nat. Rev. Microbiol., 2015, doi: 10.1038/nrmicro3459.

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 Apr;12(4):335-8.

Kudrayshev M#*, Diepold A#*, Amstutz M, Armitage JP, Stehlberg H#, Cornelis GR#, Yersinia enterocolitica type III secretion injectisomes form regularly spaced clusters which incorporate new machines upon activation, Mol. Microbiol., 2015 Mar;95(5):875-84.

Diepold A, Kudryashev M, Delalez NJ, Berry, RM, Armitage, JP, Composition, formation and regulation of the cytosolic C-ring, a dynamic component of the type III secretion injectisome, PLoS Biol, 2015 Jan; 13(1): e1002039.

Kudryashev M, Aktoudianaki A, Dedoglou D, Stahlberg H, Tsiotis G., The ultrastructure of Chlorobaculum tepidum revealed by cryo-electron tomography. Biochim Biophys Acta. 2014 Oct;1837(10):1635-42.

Schwan C, Kruppke AS, Nölke T, Schumacher L, Koch-Nolte F, Kudryashev M, Stahlberg H, Aktories K., Clostridium difficile toxin CDT hijacks microtubule organization and reroutes vesicle traffic to increase pathogen adherence, Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2313-8.

Kowal J, Chami M, Ringler P, Müller SA, Kudryashev M, Castaño-Díez D, Amstutz M, Cornelis GR, Stahlberg H, Engel A. Structure of the Dodecameric Yersinia enterocolitica Secretin YscC and Its Trypsin-Resistant Core. Structure, Dec 3; 21(12):2152-61.

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.

Degiacomi MT, Iacovache I, Chami M, Kudryashev M, Stahlberg H, van der Goot G, Dal Peraro M, The molecular assembly of the aerolysin pore reveals a swirling membrane insertion mechanism, Nat Chem Biol. 2013 Oct;9(10):623-9.

Hanssen E, Dekiwadia C, Riglar DT, Rug M, Lemgruber L, Cowman AF, Cyrklaff M, Kudryashev M, Frischknecht F, Baum J, Ralph SA., Electron tomography of Plasmodium falciparum merozoites reveals core cellular events that underpin erythrocyte invasion. Cell. Microbiol. 2013 Sep; 15(9):1457-72.

Lemgruber L*, Kudryashev M*, Dekiwadia C, Riglar DT, Baum J, Stahlberg H, Ralph SA, Frischknecht F., Cryo-electron tomography reveals four-membrane architecture of the Plasmodium apicoplast. Malaria J. 2013 Jan 19;12(1):25.

Kudryashev M, Münter S, Lemgruber L, Montagna G, Stahlberg H, Matuschewski K, Meissner M, Cyrklaff M, Frischknecht F., Structural basis for chirality and directional motility of Plasmodium sporozoites. Cell. Microbiol. 2012 Nov; 14(11):1757-68.

Maiorca M, Hanssen E, Kazmierczak E, Maco B, Kudryashev M, Hall R, Quiney H, Tilley L., Improving the quality of electron tomography image volumes using pre-reconstruction filtering. J Struct Biol. 2012 Oct; 180(1):132-42.

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.

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.

Hellmann JK, Münter S, Kudryashev M, Schulz S, Heiss K, Müller AK, Matuschewski K, Spatz JP, Schwarz US, Frischknecht F, Environmental constraints guide migration of malaria parasites during transmission, PLoS Pathog. 2011 Jun; 7(6):e1002080.

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

Kudryashev M, Cyrklaff M, Alex B, Lemgruber L, Baumeister W, Wallich R, Frischknecht F, Evidence of direct cell-cell fusion in Borrelia by cryogenic electron tomography, Cell Microbiol. 2011 May; 13(5):731-41.

  • Highlighted: van Ooij, Bacterial physiology: Wrapped up in each other, Nat. Rev. Microbiol. 9, 227; April 2011.

Hegge S*, Kudryashev M*, Barniol L*, Frischknecht F, Key factors regulating Plasmodium berghei sporozoite survival and transformation revealed by an automated visual assay, FASEB J. 2010 Dec;24(12):5003-12.

Kudryashev M, Lepper S, Baumeister W, Cyrklaff M, Frischknecht F, Geometric constrains for detecting short actin filaments by cryogenic electron tomography, PMC Biophys. 2010 Mar 5; 3(1):6.

Kudryashev M, Lepper S, Stanway R, Bohn S, Baumeister W, Cyrklaff M, Frischknecht F, Positioning of large organelles by a membrane- associated cytoskeleton in Plasmodium sporozoites, Cell. Microbiol. 2010 Mar; 12(3):362-71.

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.

Münter S*, Sabass B*, Selhuber-Unkel C*, Kudryashev M, Hegge S, Engel U, Spatz JP, Matuschewski K, Schwarz US, Frischknecht F, Plasmodium sporozoite motility is modulated by the turnover of discrete adhesion sites, Cell Host Microbe. 2009 Dec 17; 6(6):551-62.

Hegge S*, Kudryashev M*, Smith A, Frischknecht F, Automated classification of Plasmodium sporozoite motility patterns reveals the shift towards productive motility during salivary gland infection. Biotech. J. 2009 May19. Jun; 4(6):903-13.

Kudryashev M, Cyrklaff M, Baumeister W, Simon M, Wallich R, Frischknecht F, Comparative cryo-electron tomography of pathogenic Lyme disease spirochetes. Mol Microbiol,2009 Mar;7(6):1415-34.

Cyrklaff M, Kudryashev M, Leis A, Leonard K, Baumeister W, Menard R, Meissner M, Frischknecht F. Cryoelectron tomography reveals periodic material at the inner side of subpellicular microtubules in apicomplexan parasites, J. Exp. Med., 2007 Jun 11;204(6).

Garvalov BK, Zuber B, Bouchet-Marquis C, Kudryashev M, Gruska M, Beck M, Leis A, Frischknecht F, Bradke F, Baumeister W, Dubochet J, Cyrklaff M. Luminal particles within cellular microtubules, J. Cell Biol.. 2006 Sep 11; 174(6):759-65.

 

Reviews, Book Chapters

Kudryashev M#, Resolution in Electron Tomography, Book Chapter in the Springer Book on Electron Tomography, Ed. Eric Hanssen, in press

Cyrklaff M, Frischknecht F, Kudryashev M, Functional insights into pathogen biology from 3D electron microscopy, FEMS Microbiology Reviews, https://doi.org/10.1093/femsre/fux041

Gold V#, Kudryashev M#. Recent progress in structure and dynamics of dual-membrane-spanning bacterial nanomachines. Curr Opin Struct Biol. 2016 Mar 17;39:1-7.

Kudryashev M#, Castaño-Díez D, Stahlberg H, Limiting factors in single particle cryo electron tomography, Comp. Struct. Biotechnol. J., 2012, Jul; 1(2): e201207002.

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 (alumni), Misha, Eva, Daniel (alumni), Patricia, Ariane, Yingyi, Luise, Wenbo and Ricardo

Gruppenmitglieder:

Group Leader:

Postdoctoral Researchers:

Ph.D. Students:

  • Scott Chang
  • Wenbo Chen
  • Ricardo Sanchez
  • Yingyi Zhang

Research assistant:

  • Luise Eckhardt-Strelau

Master Students:

  • Robert Gebauer
  • Ariane Sahebzade

Group Alumni:

  • Daniel Schröder
    project student Sept. 2016 - March 2017,
    moved to EMBL Heidelberg for a Master Project
  • Simon Wiessing
    Master Student May 2016 - Sept 2017, moved to an industry job as a service engineer