Research Interests
Serial Crystallography and the Dynamic Nature of Proteins
My research focuses on advancing time-resolved serial crystallography at synchrotrons and free-electron lasers to investigate the structural dynamics of proteins, in particular enzymes. A key goal is to adapt and extend methods developed at XFELs for use at synchrotron sources, thereby broadening the accessibility of dynamic structural studies. By using precisely timed external triggers, I aim to synchronize conformational changes in protein crystals and capture transient intermediates with atomic spatial and high temporal resolution.
A central part of my research program targets systems that lack intrinsic photoactivity. In these cases, the challenge lies in designing alternative triggering strategies that initiate specific molecular processes in a controlled and reproducible manner. My interest lies in combining such experimental approaches with advanced computational tools to resolve overlapping structural states, reconstruct reaction coordinates, and extract kinetic information directly from time-resolved crystallographic data. This includes dimensionality reduction, spectral and correlation analyses, and machine learning-based classification methods.
By integrating methodological development with computational analysis, I aim to establish time-resolved serial crystallography as a broadly applicable tool for understanding protein dynamics under functionally relevant conditions. My long-term objective is to gain deeper insight into enzyme mechanisms and to enable the rational manipulation of protein function.
In parallel to my PI role, I also serve as a senior scientist at LBR, where I support serial crystallography and time-resolved serial crystallography activities with my extensive experience in experimental design, data acquisition, and data processing.
Curriculum Vitae
PSI Publications
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Mulder M, Hwang S, Broser M, Brünle S, Skopintsev P, Schattenberg C, et al.
Structural insights into the opening mechanism of C1C2 channelrhodopsin
Journal of the American Chemical Society. 2025; 147(1): 1282-1290. https://doi.org/10.1021/jacs.4c15402
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Bertrand Q, Nogly P, Nango E, Kekilli D, Khusainov G, Furrer A, et al.
Structural effects of high laser power densities on an early bacteriorhodopsin photocycle intermediate
Nature Communications. 2024; 15: 10278 (11 pp.). https://doi.org/10.1038/s41467-024-54422-8
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Cellini A, Shankar MK, Nimmrich A, Hunt LA, Monrroy L, Mutisya J, et al.
Directed ultrafast conformational changes accompany electron transfer in a photolyase as resolved by serial crystallography
Nature Chemistry. 2024; 16: 624-632. https://doi.org/10.1038/s41557-023-01413-9
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Glover H, Saßmannshausen T, Bertrand Q, Trabuco M, Slavov C, Bacchin A, et al.
Photoswitch dissociation from a G protein-coupled receptor resolved by time-resolved serial crystallography
Nature Communications. 2024; 15(1): 10837 (13 pp.). https://doi.org/10.1038/s41467-024-55109-w
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Gotthard G, Mous S, Weinert T, Maia RNA, James D, Dworkowski F, et al.
Capturing the blue-light activated state of the Phot-LOV1 domain from Chlamydomonas reinhardtii using time-resolved serial synchrotron crystallography
IUCrJ. 2024; 11(5): (17 pp.). https://doi.org/10.1107/S2052252524005608
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Khusainov G, Standfuss J, Weinert T
The time revolution in macromolecular crystallography
Structural Dynamics. 2024; 11(2): 020901 (17 pp.). https://doi.org/10.1063/4.0000247
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Casadei CM, Hosseinizadeh A, Bliven S, Weinert T, Standfuss J, Fung R, et al.
Low-pass spectral analysis of time-resolved serial femtosecond crystallography data
Structural Dynamics. 2023; 10(3): 034101 (18 pp.). https://doi.org/10.1063/4.0000178
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Gruhl T, Weinert T, Rodrigues MJ, Milne CJ, Ortolani G, Nass K, et al.
Ultrafast structural changes direct the first molecular events of vision
Nature. 2023; 615: 939-944. https://doi.org/10.1038/s41586-023-05863-6
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Leonarski F, Nan J, Matej Z, Bertrand Q, Furrer A, Gorgisyan I, et al.
Kilohertz serial crystallography with the JUNGFRAU detector at a fourth-generation synchrotron source
IUCrJ. 2023; 10(6): 729-737. https://doi.org/10.1107/S2052252523008618
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Maestre-Reyna M, Wang P-H, Nango E, Hosokawa Y, Saft M, Furrer A, et al.
Visualizing the DNA repair process by a photolyase at atomic resolution
Science. 2023; 382(6674): eadd7795 (14 pp.). https://doi.org/10.1126/science.add7795
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Rodrigues MJ, Casadei CM, Weinert T, Panneels V, Schertler GFX
Correction of rhodopsin serial crystallography diffraction intensities for a lattice-translocation defect
Acta Crystallographica Section D: Structural Biology. 2023; 79(3): D79 (10 pp.). https://doi.org/10.1107/S2059798323000931
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Wranik M, Kepa MW, Beale EV, James D, Bertrand Q, Weinert T, et al.
A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers
Nature Communications. 2023; 14(1): 7956 (12 pp.). https://doi.org/10.1038/s41467-023-43523-5
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Wranik M, Weinert T, Slavov C, Masini T, Furrer A, Gaillard N, et al.
Watching the release of a photopharmacological drug from tubulin using time-resolved serial crystallography
Nature Communications. 2023; 14(1): 903 (12 pp.). https://doi.org/10.1038/s41467-023-36481-5
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Cellini A, Shankar MK, Wahlgren WY, Nimmrich A, Furrer A, James D, et al.
Structural basis of the radical pair state in photolyases and cryptochromes
Chemical Communications. 2022; 58(31): 4889-4892. https://doi.org/10.1039/D2CC00376G
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Gao L, Meiring JCM, Varady A, Ruider IE, Heise C, Wranik M, et al.
In vivo photocontrol of microtubule dynamics and integrity, migration and mitosis, by the potent GFP-imaging-compatible photoswitchable reagents SBTubA4P and SBTub2M
Journal of the American Chemical Society. 2022; 144(12): 5614-5628. https://doi.org/10.1021/jacs.2c01020
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Mous S, Gotthard G, Ehrenberg D, Sen S, Weinert T, Johnson PJM, et al.
Dynamics and mechanism of a light-driven chloride pump
Science. 2022; 375(6583): 845-851. https://doi.org/10.1126/science.abj6663
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Gao L, Meiring JCM, Kraus Y, Wranik M, Weinert T, Pritzl SD, et al.
A robust, GFP-orthogonal photoswitchable inhibitor scaffold extends optical control over the microtubule cytoskeleton
Cell Chemical Biology. 2021; 28(2): 228-241. https://doi.org/10.1016/j.chembiol.2020.11.007
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Nass K, Bacellar C, Cirelli C, Dworkowski F, Gevorkov Y, James D, et al.
Pink-beam serial femtosecond crystallography for accurate structure-factor determination at an X-ray free-electron laser
IUCrJ. 2021; 8: 905-920. https://doi.org/10.1107/S2052252521008046
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Nass K, Cheng R, Vera L, Mozzanica A, Redford S, Ozerov D, et al.
Advances in long-wavelength native phasing at X-ray free-electron lasers
IUCrJ. 2020; 7: 965-975. https://doi.org/10.1107/S2052252520011379
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Skopintsev P, Ehrenberg D, Weinert T, James D, Kar RK, Johnson PJM, et al.
Femtosecond-to-millisecond structural changes in a light-driven sodium pump
Nature. 2020; 583: 314-318. https://doi.org/10.1038/s41586-020-2307-8
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Weinert T, Panneels V
Membrane protein preparation for serial crystallography using high-viscosity injectors: rhodopsin as an example
In: Perez C, Maier T, eds. Expression, purification, and structural biology of membrane proteins. Methods in molecular biology. New York: Humana; 2020:321-338. https://doi.org/10.1007/978-1-0716-0373-4_21
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Jaeger K, Bruenle S, Weinert T, Guba W, Muehle J, Miyazaki T, et al.
Structural basis for allosteric ligand recognition in the human CC chemokine receptor 7
Cell. 2019; 178(5): 1222-1230. https://doi.org/10.1016/j.cell.2019.07.028
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James D, Weinert T, Skopintsev P, Furrer A, Gashi D, Tanaka T, et al.
Improving high viscosity extrusion of microcrystals for time-resolved serial femtosecond crystallography at X-ray lasers
Journal of Visualized Experiments. 2019; 2019(144): e59087 (12 pp.). https://doi.org/10.3791/59087
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Weinert T, Skopintsev P, James D, Dworkowski F, Panepucci E, Kekilli D, et al.
Proton uptake mechanism in bacteriorhodopsin captured by serial synchrotron crystallography
Science. 2019; 365(6448): 61-65. https://doi.org/10.1126/science.aaw8634
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Aher A, Kok M, Sharma A, Rai A, Olieric N, Rodriguez-Garcia R, et al.
CLASP suppresses microtubule catastrophes through a single TOG domain
Developmental Cell. 2018; 46(1): 40-58.e8. https://doi.org/10.1016/j.devcel.2018.05.032
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Huang C-Y, Olieric V, Howe N, Warshamanage R, Weinert T, Panepucci E, et al.
In situ serial crystallography for rapid de novo membrane protein structure determination.
Communications Biology. 2018; 1: 124 (8 pp.). https://doi.org/10.1038/S42003-018-0123-6
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Nogly P, Weinert T, James D, Carbajo S, Ozerov D, Furrer A, et al.
Retinal isomerization in bacteriorhodopsin captured by a femtosecond x-ray laser
Science. 2018; 361(6398): eaat0094 (7 pp.). https://doi.org/10.1126/science.aat0094
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Tsai C-J, Pamula F, Nehmé R, Mühle J, Weinert T, Flock T, et al.
Crystal structure of rhodopsin in complex with a mini-Go sheds light on the principles of G protein selectivity
Science Advances. 2018; 4(9): aat7052 (9 pp.). https://doi.org/10.1126/sciadv.aat7052
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Jiang S, Wang L, Huang M, Jia Z, Weinert T, Warkentin E, et al.
DM9 domain containing protein functions as a pattern recognition receptor with broad microbial recognition spectrum
Frontiers in Immunology. 2017; 8: 1607 (17 pp.). https://doi.org/10.3389/fimmu.2017.01607
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Markovic-Mueller S, Stuttfeld E, Asthana M, Weinert T, Bliven S, Goldie KN, et al.
Structure of the full-length VEGFR-1 extracellular domain in complex with VEGF-A
Structure. 2017; 25(2): 341-352. https://doi.org/10.1016/j.str.2016.12.012
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Vercellino I, Rezabkova L, Olieric V, Polyhach Y, Weinert T, Kammerer RA, et al.
Role of the nucleotidyl cyclase helical domain in catalytically active dimer formation
Proceedings of the National Academy of Sciences of the United States of America PNAS. 2017; 114(46): E9821-E9828. https://doi.org/10.1073/pnas.1712621114
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Weinert T, Olieric N, Cheng R, Brünle S, James D, Ozerov D, et al.
Serial millisecond crystallography for routine room-temperature structure determination at synchrotrons
Nature Communications. 2017; 8(1): 542 (11 pp.). https://doi.org/10.1038/s41467-017-00630-4
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Huang C-Y, Olieric V, Ma P, Howe N, Vogeley L, Liu X, et al.
In meso in situ serial X-ray crystallography of soluble and membrane proteins at cryogenic temperatures
Acta Crystallographica Section D: Structural Biology. 2016; 72(1): 93-112. https://doi.org/10.1107/S2059798315021683
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Olieric V, Weinert T, Finke AD, Anders C, Li D, Olieric N, et al.
Data-collection strategy for challenging native SAD phasing
Acta Crystallographica Section D: Structural Biology. 2016; 72(3): 421-429. https://doi.org/10.1107/S2059798315024110
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Waltersperger S, Olieric V, Pradervand C, Glettig W, Salathe M, Fuchs MR, et al.
PRIGo: a new multi-axis goniometer for macromolecular crystallography
Journal of Synchrotron Radiation. 2015; 22: 895-900. https://doi.org/10.1107/S1600577515005354
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Weinert T, Olieric V, Waltersperger S, Panepucci E, Chen L, Zhang H, et al.
Fast native-SAD phasing for routine macromolecular structure determination
Nature Methods. 2015; 12(2): 131-133. https://doi.org/10.1038/nmeth.3211
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