170824 cv schertler gebhard 2 - paul scherrer institute · methods. implementing room temperature...

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Curriculum Vitae Prof. Gebhard F. X. Schertler Personal Info Citizenship Austria Date of birth 1.2.1957 Address Division of Biology and Chemistry Address line 2 Paul Scherrer Institute Town Villigen PSI Postal code 5232 Country Switzerland Email [email protected] Website URL http://www.psi.ch/bio/ Prof. Gebhard Schertler is investigating the structure and function of membrane proteins with a strong focus on G protein coupled receptors (GPCRs). When the group was located at the MRC Laboratory for Molecular Biology (Cambridge, UK), it focused on 3D structural analysis by X-ray and electron crystallography and solved the atomic structures of several GPCRs (rho- dopsin, beta adrenergic receptors). With this expertise, Schertler successfully revealed the mechanisms of light-induced rhodopsin activation and agonist-binding to a GPCR. With his move to the Paul Scherrer Institute (PSI) in Villigen, Switzerland in 2010, Schertler became the head of the division of Biology and Chemistry (BIO) at the institute and he established his inter- disciplinary research group on GPCRs in the Laboratory for Biomolecular Research (LBR). Within his group he built up strong expertise in crystallography, electron microscopy, NMR, bio- physics, bioinformatics, and protein expression/purification/crystallization. He is responsible for biological applications using the Swiss Free Electron Laser (SwissFEL) and is involved in the experimental setup and design of biology beamlines for optimization of both, biomolecular nanocrystallography and biological X-FEL imaging. He also successfully established the PSI Electron Microscopy Facility (EMF) at BIO and integrated it into LBR. In addition, he is involved in the development of the innovation area at PSI, the Park innovAARE and he has founded two spin-out companies, leadXpro and InterAx, in this context. Besides leading the BIO division at PSI, Schertler is a member of the Board of Directors at the PSI and he is full Professor for Structural Biology at the ETH in Zürich, Switzerland. Major achievements Major contributions to the structure of visual pigments and GPCRs us- ing electron microscopy and high brilliance X-ray micro-diffraction methods. Implementing room temperature crystallography at FELs for retinal proteins.

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Curriculum Vitae

Prof. Gebhard F. X. Schertler

Personal Info Citizenship Austria Date of birth 1.2.1957 Address Division of Biology and Chemistry Address line 2 Paul Scherrer Institute Town Villigen PSI Postal code 5232 Country Switzerland Email [email protected] Website URL http://www.psi.ch/bio/

Prof. Gebhard Schertler is investigating the structure and function of membrane proteins with a strong focus on G protein coupled receptors (GPCRs). When the group was located at the MRC Laboratory for Molecular Biology (Cambridge, UK), it focused on 3D structural analysis by X-ray and electron crystallography and solved the atomic structures of several GPCRs (rho-dopsin, beta adrenergic receptors). With this expertise, Schertler successfully revealed the mechanisms of light-induced rhodopsin activation and agonist-binding to a GPCR. With his move to the Paul Scherrer Institute (PSI) in Villigen, Switzerland in 2010, Schertler became the head of the division of Biology and Chemistry (BIO) at the institute and he established his inter-disciplinary research group on GPCRs in the Laboratory for Biomolecular Research (LBR). Within his group he built up strong expertise in crystallography, electron microscopy, NMR, bio-physics, bioinformatics, and protein expression/purification/crystallization. He is responsible for biological applications using the Swiss Free Electron Laser (SwissFEL) and is involved in the experimental setup and design of biology beamlines for optimization of both, biomolecular nanocrystallography and biological X-FEL imaging. He also successfully established the PSI Electron Microscopy Facility (EMF) at BIO and integrated it into LBR. In addition, he is involved in the development of the innovation area at PSI, the Park innovAARE and he has founded two spin-out companies, leadXpro and InterAx, in this context. Besides leading the BIO division at PSI, Schertler is a member of the Board of Directors at the PSI and he is full Professor for Structural Biology at the ETH in Zürich, Switzerland.

Major achievements Major contributions to the structure of visual pigments and GPCRs us-

ing electron microscopy and high brilliance X-ray micro-diffraction methods. Implementing room temperature crystallography at FELs for retinal proteins.

Keywords structures of beta 1-adrenergic receptor with agonists and antagonists structure of beta 2-adrenergic receptor structures of active and inactive rhodopsin by X-ray crystallography structure of rhodopsin by cryo-EM (2D and 3D) development of micro crystallography

Education University of Munich, PhD, 1989, Biochemistry University of Innsbruck, Diploma, 1984, Chemistry

Positions held Member of Directorial Board, Paul Scherrer Institute (PSI), 2011 - Head of Division of Biology and Chemistry, PSI, 2010 - Head of Laboratory of Biomolecular Research, PSI, 2010 -2012 Full Professor of Structural Biology, ETH Zürich, 2010 - Group Leader, MRC-LMB Cambridge, 1998 - 2010 Staff Scientist, MRC-LMB Cambridge, 1991 - 1998 EMBO fellow, MRC-LMB Cambridge, 1989 -1991

Honors and Awards Research fellowship, Clare Hall, 1996 EMBO long term fellowship, Richard Henderson, 1989

Editorial Activities Editor of Membrane Protein Section, Current Opinion in Structural Bi-ology 2011

Organizational Chair, International Retinal Protein Conference 2012Activities Chair, Gordon Conference, Ligand Recognition and Molecular Gating,

2002 Advisory Board Member of Directorial Board, Paul Scherrer Institute, Villigen(past and present) Scientific Advisory Board, leadXpro AG, Switzerland (2015 - ) Scientific Advisory Board, InterAx Biotech, Switzerland (2015 - ) Scientific Advisory Board, Heptares Pharmaceuticals, UK (2007 - 2014)

International Retinal Protein Conference (1998 - ) Scientific advisory committee of MAX IV Laboratory, Sweden (2010 - )

Invited presentations More than hundred conference, workshop or invited presentations since 1989.

More than ten oral presentations per year during the last 15 years.

Publications Total publications = 118; Total citations = 12077; 24 publications ≥ 100 citations. I10 index = 69; H-­‐index = 40; Average Citations per Item = 102.35 (Source data: Google Scholar)

Publications since 2010, for the full publication list, please go to https://www.psi.ch/lbr/schertler-gerhard:

Serial millisecond crystallography for routine room- temperature structure determination at synchrotronsT Weinert, N Olieric, R Cheng, S Brünle, D James, D Ozerov, D Gashi, L Vera, M Marsh, K Jaeger, F Dworkowski, E Panepucci, S Basu, P Skopintsev, A Doré, T Geng, RM Cooke, M Liang, AE Prota, V Panneels, P Nogly, U Ermler, G Schertler, M Hennig, MO Steinmetz, Me Wang & J StandfussNature Communications accepted DOI: 10.1038/s41467-017-00630-4 A three-dimensional movie of structural changes in bacteriorhodopsinM Kubo, T Nakane, C Wickstrand, T Kimura, T Tanaka, K Tono, C Song, R Tanaka, T Arima, A Yamashita, J Kobayashi, T Hosaka, E Mizohata, P Nogly, M Sugahara, D Nam, T No-mura, T Shimamura, D Im, T Fujiwara, Y Yamanaka, B Jeon, T Nishizawa, K Oda, M Fu-kuda, R Andersson, P Bath, R Dods, J Davidsson, S Matsuoka, S Kawatake, M Murata, O Nureki, S Owada, T Kameshima, T Hatsui, Y Joti, G Schertler, M Yabashi, AN Bondar, J Standfuss, R Neutze and S IwataScience 354, 1552-1557 (2016). Diverse activation pathways in class a GPCRs converge near the G-protein-coupling regionAJ Venkatakrishnan, X Deupi, G Lebon, FM Heydenreich, T Flock, T Miljus, S Balaji, M Bouvier, DB Veprintsev, CG Tate, GF Schertler and MM BabuNature 536, 484-487 (2016). Structural role of the T94I rhodopsin mutation in congenital stationary night blindnessA Singhal, Y Guo, M Matkovic, G Schertler, X Deupi, EC Yan and J StandfussEMBO Rep 17, 1431-1440 (2016). Lipidic cubic phase injector is a viable crystal delivery system for time-resolved serial crys-tallographyP Nogly, V Panneels, G Nelson, C Gati, T Kimura, C Milne, D Milathianaki, M Kubo, W Wu, C Conrad, J Coe, R Bean, Y Zhao, P Bath, R Dods, R Harimoorthy, KR Beyerlein, J Rheinberger, D James, D DePonte, C Li, L Sala, GJ Williams, MS Hunter, JE Koglin, P Berntsen, E Nango, S Iwata, HN Chapman, P Fromme, M Frank, R Abela, S Boutet, A Barty, TA White, U Weierstall, J Spence, R Neutze, G Schertler and J StandfussNat Commun 7, 12314 (2016). Backbone NMR reveals allosteric signal transduction networks in the beta 1 adrenergic re-ceptorS Isogai, X Deupi, C Opitz, FM Heydenreich, CJ Tsai, F Brueckner, GF Schertler, DB Veprintsev and S GrzesiekNature 530, 237-241 (2016). Complete reversible refolding of a G-protein coupled receptor on a solid supportN Di Bartolo, EL Compton, T Warne, PC Edwards, CG Tate, GF Schertler and PJ BoothPLoS One 11, e0151582 (2016). Conformational selection in a protein-protein interaction revealed by dynamic pathway analysisKS Chakrabarti, RV Agafonov, F Pontiggia, R Otten, MK Higgins, GF Schertler, DD Oprian and D KernCell Rep 14, 32-42 (2016). Batch crystallization of rhodopsin for structural dynamics using an X-ray free-electron laserW Wu, P Nogly, J Rheinberger, LM Kick, C Gati, G Nelson, X Deupi, J Standfuss,

G Schertler and V PanneelsActa Crystallogr F Struct Biol Commun 71, 856-860 (2015). Probing G alpha i1 protein activation at single-amino acid resolutionD Sun, T Flock, X Deupi, S Maeda, M Matkovic, S Mendieta, D Mayer, RJ Dawson, GF Schertler, MM Babu and DB VeprintsevNat Struct Mol Biol 22, 686-694 (2015). Rhodopsin on tracks: New ways to go in signalingGF SchertlerStructure 23, 606-608 (2015). Time-resolved structural studies with serial crystallography: A new light on retinal proteinsV Panneels, W Wu, CJ Tsai, P Nogly, J Rheinberger, K Jaeger, G Cicchetti, C Gati, LM Kick, L Sala, G Capitani, C Milne, C Padeste, B Pedrini, XD Li, J Standfuss, R Abela and G SchertlerStruct Dyn 2, 041718 (2015). Lipidic cubic phase serial millisecond crystallography using synchrotron radiationP Nogly, D James, D Wang, TA White, N Zatsepin, A Shilova, G Nelson, H Liu, L Johansson, M Heymann, K Jaeger, M Metz, C Wickstrand, W Wu, P Bath, P Berntsen, D Oberthuer, V Panneels, V Cherezov, H Chapman, G Schertler, R Neutze, J Spence, I Moraes, M Burghammer, J Standfuss and U WeierstallIUCrJ 2, 168-176 (2015). Membrane protein structural biology using X-ray free electron lasersR Neutze, G Branden and GF SchertlerCurr Opin Struct Biol 33, 115-125 (2015). Conformational activation of visual rhodopsin in native disc membranesE Malmerberg, MB-G PH, G Katona, X Deupi, D Arnlund, C Wickstrand, LC Johansson, S Westenhoff, E Nazarenko, GF Schertler, A Menzel, WJ de Grip and R NeutzeSci Signal 8, ra26 (2015). GPCR structure, function, drug discovery and crystallography: Report from academia-industry international conference (UK Royal Society)A Heifetz, GF Schertler, R Seifert, CG Tate, PM Sexton, VV Gurevich, D Fourmy, V Cherezov, FH Marshall, RI Storer, I Moraes, IG Tikhonova, CS Tautermann, P Hunt, T Ceska, S Hodgson, MJ Bodkin, S Singh, RJ Law and PC BigginNaunyn Schmiedebergs Arch Pharmacol 388, 883-903 (2015). Large scale expression and purification of the rat 5-HT2c receptorX He, N Robertson, A Jazayeri, AG Gasperina, G Schertler and X LiProtein Expr Purif 106, 1-9 (2015). Three-dimensional mass density mapping of cellular ultrastructure by ptychographic X-ray nanotomographyA Diaz, B Malkova, M Holler, M Guizar-Sicairos, E Lima, V Panneels, G Pigino, AG Bitter-mann, L Wettstein, T Tomizaki, O Bunk, G Schertler, T Ishikawa, R Wepf and A MenzelJ Struct Biol 192, 461-469 (2015). 7 angstrom resolution in protein two-dimensional-crystal X-ray diffraction at linac coherent light sourceB Pedrini, CJ Tsai, G Capitani, C Padeste, MS Hunter, NA Zatsepin, A Barty, WH Benner, S Boutet, GK Feld, SP Hau-Riege, RA Kirian, C Kupitz, M Messerschmitt, JI Ogren, T Pardini, B Segelke, GJ Williams, JC Spence, R Abela, M Coleman, JE Evans, GF Schertler, M Frank and XD LiPhilos Trans R Soc Lond B Biol Sci 369, 20130500 (2014).

Molecular mechanism of phosphorylation-dependent arrestin activationMK Ostermaier, GF Schertler and J StandfussCurr Opin Struct Biol 29C, 143-151 (2014). The 2.1 angstrom resolution structure of cyanopindolol-bound beta 1-adrenoceptor identi-fies an intramembrane na+ ion that stabilises the ligand-free receptorJL Miller-Gallacher, R Nehme, T Warne, PC Edwards, GF Schertler, AG Leslie and CG TatePLoS One 9, e92727 (2014). Crystallization scale preparation of a stable GPCR signaling complex between constitutively active rhodopsin and G-proteinS Maeda, D Sun, A Singhal, M Foggetta, G Schmid, J Standfuss, M Hennig, RJ Dawson, DB Veprintsev and GF SchertlerPLoS One 9, e98714 (2014). Advancing membrane protein crystallography using the LCLSM Hunter, BW Segelke, N Zatsepin, M Coleman, WH Benner, S Hauriege, C-J Tsai, X-d Li, B Pedrini and G SchertlerPROTEIN SCIENCE 23, 236-237 (2014). Retinal proteins - you can teach an old dog new tricksJ Heberle, X Deupi and G SchertlerBiochim Biophys Acta 1837, 531-532 (2014). Femtosecond X-ray diffraction from two-dimensional protein crystalsM Frank, DB Carlson, MS Hunter, GJ Williams, M Messerschmidt, NA Zatsepin, A Barty, WH Benner, K Chu, AT Graf, SP Hau-Riege, RA Kirian, C Padeste, T Pardini, B Pedrini, B Segelke, MM Seibert, JC Spence, CJ Tsai, SM Lane, XD Li, G Schertler, S Boutet, M Coleman and JE EvansIUCrJ 1, 95-100 (2014). Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin ARM Benoit, D Frey, M Hilbert, JT Kevenaar, MM Wieser, CU Stirnimann, D McMillan, T Ceska, F Lebon, R Jaussi, MO Steinmetz, GF Schertler, CC Hoogenraad, G Capitani and RA KammererNature 505, 108-111 (2014). Constitutively active rhodopsin mutants causing night blindness are effectively phosphory-lated by GRKs but differ in arrestin-1 bindingSA Vishnivetskiy, MK Ostermaier, A Singhal, V Panneels, KT Homan, A Glukhova, SG Sligar, JJ Tesmer, GF Schertler, J Standfuss and VV GurevichCell Signal 25, 2155-2162 (2013). Molecular signatures of G-protein-coupled receptorsAJ Venkatakrishnan, X Deupi, G Lebon, CG Tate, GF Schertler and MM BabuNature 494, 185-194 (2013). Two alternative conformations of a voltage-gated sodium channelCJ Tsai, K Tani, K Irie, Y Hiroaki, T Shimomura, DG McMillan, GM Cook, GF Schertler, Y Fujiyoshi and XD LiJ Mol Biol 425, 4074-4088 (2013). Insights into congenital stationary night blindness based on the structure of G90D rhodop-sinA Singhal, MK Ostermaier, SA Vishnivetskiy, V Panneels, KT Homan, JJ Tesmer, D Veprintsev, X Deupi, VV Gurevich, GF Schertler and J StandfussEMBO Rep 14, 520-526 (2013).

Production of GPCRs and GPCR complexes for structure determinationS Maeda and GF SchertlerCurr Opin Struct Biol 23, 381-392 (2013). Structure of beta-adrenergic receptorsF Brueckner, CL Piscitelli, CJ Tsai, J Standfuss, X Deupi and GF SchertlerMethods Enzymol 520, 117-151 (2013). Conserved activation pathways in G-protein-coupled receptorsX Deupi, J Standfuss and G SchertlerBiochem Soc Trans 40, 383-388 (2012). Ligands stabilize specific GPCR conformations: But how?X Deupi, XD Li and GF SchertlerStructure 20, 1289-1290 (2012). Stabilized G protein binding site in the structure of constitutively active metarhodopsin-IIX Deupi, P Edwards, A Singhal, B Nickle, D Oprian, G Schertler and J StandfussProc Natl Acad Sci U S A 109, 119-124 (2012). Preparation of an activated rhodopsin/transducin complex using a constitutively active mu-tant of rhodopsinG Xie, AM D'Antona, PC Edwards, M Fransen, J Standfuss, GF Schertler and DD OprianBiochemistry 50, 10399-10407 (2011). The structural basis for agonist and partial agonist action on a beta 1 adrenergic receptorT Warne, R Moukhametzianov, JG Baker, R Nehme, PC Edwards, AG Leslie, GF Schertler and CG TateNature 469, 241-244 (2011). Adaptation of pineal expressed teleost exo-rod opsin to non-image forming photoreception through enhanced meta II decayEE Tarttelin, MP Fransen, PC Edwards, MW Hankins, GF Schertler, R Vogel, RJ Lucas and J BellinghamCell Mol Life Sci 68, 3713-3723 (2011). MembranesRM Stroud and GF SchertlerCurr Opin Struct Biol 21, 495-496 (2011). The structural basis of agonist-induced activation in constitutively active rhodopsinJ Standfuss, PC Edwards, A D'Antona, M Fransen, G Xie, DD Oprian and GF SchertlerNature 471, 656-660 (2011). Two distinct conformations of helix 6 observed in antagonist-bound structures of a beta 1 adrenergic receptorR Moukhametzianov, T Warne, PC Edwards, MJ Serrano-Vega, AG Leslie, CG Tate and GF SchertlerProc Natl Acad Sci U S A 108, 8228-8232 (2011).

"4D biology for health and disease" workshop reportJP Abrahams, R Apweiler, R Balling, MG Bertero, JM Bujnicki, NE Chayen, P Chene, GL Corthals, T Dylag, F Forster, AJ Heck, PJ Henderson, R Herwig, P Jehenson, SJ Kokalj, E Laue, P Legrain, L Martens, C Migliorini, A Musacchio, M Podobnik, GF Schertler, G Schreiber, TK Sixma, AB Smit, D Stuart, DI Svergun and MJ TaussigN Biotechnol 28, 291-293 (2011).

Tracking G-protein-coupled receptor activation using genetically encoded infrared probes

S Ye, E Zaitseva, G Caltabiano, GF Schertler, TP Sakmar, X Deupi and R VogelNature 464, 1386-1389 (2010).

Spial: Analysis of subtype-specific features in multiple sequence alignments of proteinsA Wuster, AJ Venkatakrishnan, GF Schertler and MM BabuBioinformatics 26, 2906-2907 (2010).