Dr. Guillaume Cyril Gotthard


Beamline Scientist

Paul Scherrer Institut
Forschungsstrasse 111
5232 Villigen PSI


Guillaume Gotthard is an accomplished scientist with a strong academic background in Structural Biology. He completed his Bachelor's degree in Biochemistry, followed by a Master's degree in Structural Biology at the renowned Université de la Méditerranée (Marseille, France). His deep interest in structural biochemistry led him to pursue a Ph.D. a, where he successfully defended his thesis in 2013, on the structure-guided engineering of hyperthermophilic phosphotriesterase and lactonase enzymes.

In 2014, Guillaume joined the Structural Biology group at the European Synchrotron Radiation Facility (ESRF, Grenoble, France). Under the guidance of Dr. Antoine Royant, he played a pivotal role in the development of the in crystallo optical spectroscopy (icOS) beamline as a postdoctoral and junior scientist. This experience allowed him to contribute to cutting-edge research and further his expertise in various scientific fields such as Fluorescent proteins, X-ray Radiation damage and Room Temperature crystallography.

In 2019, Guillaume received a prestigious PSI-Marie Skłodowska Curie Fellowship, where he joined the group of Pr. Gebhard Schertler (PSI) and worked under the guidance of Dr. Przemyslaw Nogly (ETH Zürich). During this period, Guillaume focused on topics related to time-resolved serial crystallography at synchrotrons and X-ray Free Electron Lasers, making significant contributions to the field.

Currently, Guillaume holds the position of Beamline Scientist in the MX group at the Swiss Light Source. Leveraging his expertise and experience, he continues to contribute to groundbreaking research and advancements in the field of structural biology.

Scientific Research

Guillaume Gotthard's scientific research journey has been marked by a strong focus on methodology topics at synchrotron facilities. In 2014, he developed a keen interest in the domain of room temperature and X-ray induced radiation damage. This early exploration allowed him to acquire valuable expertise in understanding and mitigating the effects of radiation damage in crystallography experiments.

Building upon this foundation, in 2019, Guillaume became deeply involved in several impactful projects in the field of time-resolved crystallography at synchrotrons and X-ray Free Electron Lasers (X-FEL). His contributions to these projects have expanded our understanding of ultrafast structural dynamics in biomolecules, paving the way for exciting advancements in the field. Today, as a beamline scientist in the MX group, Guillaume leverages his extensive experience and expertise in these fields to support users at the Cristallina experimental station of SwissFEL and the PX beamlines of SLS.


Ultrafast structural changes direct the first molecular events of vision. Gruhl, T., Weinert, T., Rodrigues, M., Milne, C. J., Ortolani, G., Nass, K., Nango, E., Sen, S., Johnson, P. J. M., Cirelli, C., Furrer, A., Mous, S., Skopintsev, P., James, D., Dworkowski, F., Båth, P., Kekilli, D., Ozerov, D., Tanaka, R., Glover, H., Bacellar, C., Brünle, S., Casadei, C. M., Diethelm, A. D., Gashi, D., Gotthard, G., Guixà-González, R., Joti, Y., Kabanova, V., Knopp, G., Lesca, E., Ma, P., Martiel, I., Mühle, J., Owada, S., Pamula, F., Sarabi, D., Tejero, O., Tsai, C.-J., Varma, N., Wach, A., Boutet, S., Tono, K., Nogly, P., Deupi, X., Iwata,
S., Neutze, R., Standfuss, J., Schertler, G. F., Panneels, V. & Leiden. Nature 615, 939–944. (2023).

Slow protein dynamics probed by time-resolved oscillation crystallography at room temperature. Aumonier, S., Engilberge, S., Caramello, N., von Stetten, D., Gotthard, G., Leonard, G. A., Mueller-Dieckmann, C. & Royant, A. IUCrJ 9 (6 Nov. 2022).

Dynamics and mechanism of a light-driven chloride pump. Mous, S., Gotthard, G., Ehrenberg, D., Sen, S., Weinert, T., Johnson, P. J. M., James, D., Nass, K., Furrer, A., Kekilli, D., Ma, P., Brünle, S., Casadei, C. M., Martiel, I., Dworkowski, F., Gashi, D., Skopintsev, P., Wranik, M., Knopp, G., Panepucci, E., Panneels, V., Cirelli, C., Ozerov, D., Schertler, G. F. X., Wang, M., Milne, C., Standfuss, J., Schapiro, I., Heberle, J. & Nogly, P. Science 375, 845–851. (Feb. 2022).

Riboflavin-binding proteins for singlet oxygen production. Photochemical Photobiological Sciences. Lafaye, C., Aumonier, S., Torra, J., Signor, L., von Stetten, D., Noirclerc-Savoye, M., Shu, X., Ruiz-González, R., Gotthard, G., Royant, A. & Nonell, S. (Jan. 2022).

Kinetic and Structural Characterization of the Self-Labeling Protein Tags HaloTag7, SNAP-tag, and CLIP-tag. Wilhelm, J., Kühn, S., Tarnawski, M., Gotthard, G., Tünnermann, J., Tänzer, T., Karpenko, J., Mertes, N., Xue, L., Uhrig, U., Reinstein, J., Hiblot, J. & Johnsson, K. Biochemistry, acs.biochem.1c00258. (Aug. 2021).

Mechanism and dynamics of fatty acid photodecarboxylase. Sorigué, D., Hadjidemetriou, K., Blangy, S., Gotthard, G., Bonvalet, A., Coquelle, N., Samire, P., Aleksandrov, A., Antonucci, L., Benachir, A., Boutet, S., Byrdin, M., Cammarata, M., Carbajo, S., Cuiné, S., Doak, R. B., Foucar, L., Gorel, A., Grünbein, M., Hartmann, E., Hienerwadel, R., Hilpert, M., Kloos, M., Lane, T. J., Légeret, B., Legrand, P., Li-Beisson, Y., Moulin, S. L. Y., Nurizzo, D., Peltier, G., Schirò, G., Shoeman, R. L., Sliwa, M., Solinas, X., Zhuang, B., Barends, T. R. M., Colletier, J.-P., Joffre, M., Royant, A., Berthomieu, C., Weik, M., Domratcheva, T., Brettel, K., Vos, M. H., Schlichting, I., Arnoux, P., Müller, P. & Beisson, F. Science 372, eabd5687. (2021).

Mechanistic Investigations of Green mEos4b Reveal a Dynamic Long-Lived Dark State. De Zitter, E., Ridard, J., Thédié, D., Adam, V., Lévy, B., Byrdin, M., Gotthard, G., Van Meervelt, L., Dedecker, P., Demachy, I. & Bourgeois, D. Journal of the American Chemical Society 142, 10978–10988. (2020).

Aequorea’s secrets revealed: New fluorescent proteins with unique properties for bioimaging and biosensing. Lambert, G. G., Depernet, H., Gotthard, G., Schultz, D. T., Navizet, I., Lambert, T., Adams, S. R., Torreblanca-Zanca, A., Chu, M., Bindels, D. S., Levesque, V., Moffatt, J. N., Salih, A., Royant, A. & Shaner, N. C. PLoS Biology 18, 1–22. (2020).

Millisecond time-resolved serial oscillation crystallography of a blue-light photoreceptor at a synchrotron. Aumonier, S., Santoni, G., Gotthard, G., von Stetten, D., Leonard, G. A. & Royant, A. IUCrJ 7, 728–736. (July 2020).

Selecting the first chemical molecule inhibitor of HSP110 for colorectal cancer therapy. Gozzi, G. J., Gonzalez, D., Boudesco, C., Dias, A. M. M., Gotthard, G., Uyanik, B., Dondaine, L., Marcion, G., Hermetet, F., Denis, C., Hardy, L., Suzanne, P., Douhard, R., Jego, G., Dubrez, L., Demidov, O. N., Neiers, F., Briand, L., Sopková-de Oliveira Santos, J., Voisin-Chiret, A.-S. & Garrido, C. Cell Death & Differentiation 27, 117–129. (Jan. 2020).

The Drosophila odorant-binding protein 28a is involved in the detection of the floral odour ß-ionone. Gonzalez, D., Rihani, K., Neiers, F., Poirier, N., Fraichard, S., Gotthard, G., Chertemps, T., Maïbèche, M., Ferveur, J.-F. & Briand, L. Cellular and Molecular Life Sciences 77, 2565–2577. (July 2020).

Specific radiation damage is a lesser concern at room temperature. Gotthard, G., Aumonier, S., De Sanctis, D., Leonard, G., von Stetten, D. & Royant, A. IUCrJ 6, 665–680. (July 2019).

Structure Solution of the Fluorescent Protein Cerulean Using MeshAndCollect. Hutin, S., Santoni, G., Zander, U., Foos, N., Aumonier, S., Gotthard, G., Royant, A., Mueller-Dieckmann, C. & Leonard, G. Journal of Visualized Experiments, 1–7. (Mar. 2019).

Dynamics of a family of cyan fluorescent proteins probed by incoherent neutron scattering. Golub, M., Guillon, V., Gotthard, G., Zeller, D., Martinez, N., Seydel, T., Koza, M. M., Lafaye, C., Clavel, D., von Stetten, D., Royant, A. & Peters, J. Journal of The Royal Society Interface 16, 20180848. (Mar. 2019).

Tailing miniSOG: structural bases of the complex photophysics of a flavin-binding singlet oxygen photo-sensitizing protein. Torra, J., Lafaye, C., Signor, L., Aumonier, S., Flors, C., Shu, X., Nonell, S., Gotthard, G. & Royant, A. Scientific Reports 9, 2428. (Dec. 2019).

Tracking the route of molecular oxygen in O2-tolerant membrane-bound [NiFe] hydrogenase. Kalms, J., Schmidt, A., Frielingsdorf, S., Utesch, T., Gotthard, G., von Stetten, D., van der Linden, P., Royant, A., Mroginski, M. A., Carpentier, P., Lenz, O. & Scheerer, P. Proceedings of the National Academy of Sciences of the United States of America 115, E2229–E2237. (2018).

Recombinant expression of Mimivirus L725 ORFan gene product. Sobhy, H., Gotthard, G., Chabrière, E., Raoult, D. & Colson, P. Acta Virologica 61, 123–126. (2017).

Chromophore Isomer Stabilization Is Critical to the Efficient Fluorescence of Cyan Fluorescent Proteins. Gotthard, G., von Stetten, D., Clavel, D., Noirclerc-Savoye, M. & Royant, A. Biochemistry 56, 6418–6422. (Dec. 2017).

Rational engineering of a native hyperthermostable lactonase into a broad spectrum phosphotriesterase. Jacquet, P., Hiblot, J., Daudé, D., Bergonzi, C., Gotthard, G., Armstrong, N., Chabrière, E. & Elias, M. Scientific Reports 7, 16745. ISSN: 2045-2322. (2017).

Serial Femtosecond Crystallography and Ultrafast Absorption Spectroscopy of the Photoswitchable Fluorescent Protein IrisFP. Colletier, J. P., Sliwa, M., Gallat, F. X., Sugahara, M., Guillon, V., Schirò, G., Coquelle, N., Woodhouse, J., Roux, L., Gotthard, G., Royant, A., Uriarte, L. M., Ruckebusch, C., Joti, Y., Byrdin, M., Mizohata, E., Nango, E., Tanaka, T., Tono, K., Yabashi, M., Adam, V., Cammarata, M., Schlichting, I., Bourgeois, D. & Weik, M.Journal of Physical Chemistry Letters 7, 882–887. (2016).

MScarlet: A bright monomeric red fluorescent protein for cellular imaging. Bindels, D. S., Haarbosch, L., Van Weeren, L., Postma, M., Wiese, K. E., Mastop, M., Aumonier, S., Gotthard, G., Royant, A., Hink, M. A. & Gadella, T. W. Nature Methods 14, 53–56. (2016).

Structural analysis of the bright monomeric yellow-green fluorescent protein mNeonGreen obtained by directed evolution. Clavel, D., Gotthard, G., von Stetten, D., De Sanctis, D., Pasquier, H., Lambert, G. G., Shaner, N. C. & Royant, A. Acta Crystallographica Section D Structural Biology 72, 1298–1307. (2016).

Surface plasmon resonance imaging of pathogens: the Yersinia pestis paradigm. Huynh, H. T. T., Gotthard, G., Terras, J., Aboudharam, G., Drancourt, M. & Chabrière, E. BMC Research Notes 8, 259. (Dec. 2015).

Ancestral mutations as a tool for solubilizing proteins: The case of a hydrophobic phosphate-binding protein. Gonzalez, D., Hiblot, J., Darbinian, N., Miller, J. C., Gotthard, G., Amini, S., Chabriere, E. & Elias, M. FEBS Open Bio 4, 121–127. (2014).

Long-range DHPS mutations unexpectedly increase Mycobacterium chimaera susceptibility to sulfonamides. Gotthard, G., Muhammed Ameen, S., Drancourt, M. & Chabriere, E. Journal of Global Antimicrobial Resistance 1, 181–188. (2013).

Crystallization and preliminary X-ray diffraction analysis of a high-affinity phosphate-binding protein endowed with phosphatase activity from Pseudomonas aeruginosa PAO1. Djeghader, A., Gotthard, G., Suh, A., Gonzalez, D., Scott, K., Chabriere, E. & Elias, M. Acta Crystallogr Sect F Struct Biol Cryst Commun 69, 1143–1146 (2013).

Crystallization and preliminary X-ray diffraction analysis of a DING protein from Pseudomonas aeruginosa PA14. Djeghader, A., Gotthard, G., Suh, A., Gonzalez, D., Scott, K., Elias, M. & Chabriere, E. Acta Crystallogr Sect F Struct Biol Cryst Commun 69, 425–429. (2013).

Crystallization and preliminary X-ray diffraction analysis of the organophosphorus hydrolase OPHC2 from Pseudomonas pseudoalcaligenes. Gotthard, G., Hiblot, J., Gonzalez, D., Chabrière, E. & Elias, M. Acta Crystallographica Section F: Structural Biology and Crystallization Communications 69, 73–76. (2013).

Differential Active Site Loop Conformations Mediate Promiscuous Activities in the Lactonase SsoPox. Hiblot, J., Gotthard, G., Elias, M. & Chabriere, E. PLoS ONE 8, e75272. (Sept. 2013).

Crystallization and preliminary X-ray diffraction analysis of the lactonase VmoLac from Vulcanisaeta moutnovskia. Hiblot, J., Gotthard, G., Champion, C., Chabriere, E. & Elias, M. Acta Crystallographica Section F: Structural Biology and Crystallization Communications 69, 1235–1238 (2013).

Structural and enzymatic characterization of the phosphotriesterase OPHC2 from Pseudomonas pseudoalcaligenes. Gotthard, G., Hiblot, J., Gonzalez, D., Elias, M. & Chabriere, E. PLoS ONE 8 (2013).

The Level of DING Proteins Is Increased in HIV-Infected Patients: In Vitro and In Vivo Studies. Djeghader, A., Aragonès, G., Darbinian, N., Elias, M., Gonzalez, D., García-Heredia, A., Beltrán-Debón, R., Kaminski, R., Gotthard, G., Hiblot, J., Rull, A., Rohr, O., Schwartz, C., Alonso-Villaverde, C., Joven, J., Camps, J. & Chabriere, E. PLoS ONE 7, e33062. (Mar. 2012).

Structural and Enzymatic characterization of the lactonase SisLac from Sulfolobus islandicus. Hiblot, J., Gotthard, G., Chabriere, E. & Elias, M. PLoS ONE 7, e47028. (Oct. 2012).

Characterisation of the organophosphate hydrolase catalytic activity of SsoPox. Hiblot, J., Gotthard, G., Chabriere, E. & Elias, M. Scientific Reports 2, 779. (Dec. 2012).

Crystallization and preliminary X-ray diffraction analysis of the hyperthermophilic Sulfolobus islandicus lactonase. Gotthard, G., Hiblot, J., Elias, M., Chabrière, E. & Chabrire, E. Acta Crystallographica Section F Structural Biology and Crystallization Communications 67, 354–357. (Mar. 2011).

Human-Phosphate-Binding-Protein inhibits HIV-1 gene transcription and replication. Cherrier, T., Elias, M., Jeudy, A., Gotthard, G., Le Douce, V., Hallay, H., Masson, P., Janossy, A., Candolfi, E., Rohr, O., Chabrière, E. & Schwartz, C. Virology journal 8, 352 (2011).

Structural insights and ab initio sequencing within the DING proteins family. Elias, M., Liebschner, D., Gotthard, G. & Chabriere, E. Journal of Synchrotron Radiation 18 (2011), 45–49.

Eukaryotic DING Proteins Are Endogenous: An Immunohistological Study in Mouse Tissues. Collombet, J.-M., Elias, M., Gotthard, G., Four, E., Renault, F., Joffre, A., Baubichon, D., Rochu, D. & Chabrière, E. PLoS ONE 5, e9099. (Feb. 2010).