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Institution: IBMB
Research Groups: Synthetic Structural Biology
Position: Group Leader
Home page: https://ibmb.csic.es/en/department-of-structural-and-molecular-biology/synthetic-structural-biology/
Contact email: ulrich.eckhard@ibmb.csic.es
BCB Committee: No committees assigned.
BCB Community: No communities assigned.
BCB Tools: No tools assigned.
BCB Services: No services assigned.
Research topics: Structural bioinformatics, Experimental structure determination, Protein/Nucleic Acid design
Biography: Current Research Position. I joined the IBMB-CSIC in Barcelona in 2019 through the Beatriu de Pinós MSCA COFUND program, and since 2022, I have been a Ramon y Cajal Research Investigator and Group Leader of the Synthetic Structural Biology Lab. My research lies at the interface of structural biochemistry, protein biotechnology, and synthetic microbiology. My group focuses on three core areas: redesigning proteolytic flagellins to harness flagellar display for biotechnology and biomedicine (PID2021-128682OA-I00), investigating the role of proteases and inhibitors in health and disease (RYC2020-029773-I; 2021SGR00423; CNS2024-154537), and enzyme engineering and protein design for BioMedTech (MMT24-IBMB-01; PLEC2023-010243).
Research Trajectory. I have a strong track record in the structural biochemistry of enzymes with high potential biotechnological applications and implications in health and disease, and have consistently demonstrated high productivity in four different countries. During my PhD at the University of Salzburg, Austria (2007-2011; 7 publications), I focused on clostridial collagenases, key pathogenicity factors (Eckhard et al. 2011, Nature Structural & Molecular Biology), while during my postdoc at the University of British Columbia in Vancouver, Canada (2011-2016; 20 publications), I comprehensively characterized the human matrix metalloprotease family, key signaling scissors during inflammation and tumor development (e.g., Eckhard et al. 2016, Matrix Biology), and used state-of-the-art proteomic technologies to identify proteolytic signatures in human tissues (e.g., Eckhard et al. 2015, Journal of Proteome Research). Moreover, I led the discovery and characterization of flagella-embedded proteolysis, nature's proof of flagellar display (Eckhard et al. 2017, Nature Communications), and the cornerstone of my current core research line – the flagellar display of enzymes for biotechnological applications. I then joined Uppsala University (2016-2017; 3 publications) where I tackled the overarching question of how protein structure and function are intertwined during evolution and ecological adaptation, before returning to the University of Salzburg (2017-2019; 2 publications) to focus on the biochemistry and role of proteolytic flagellins in bacterial lifestyle.
Training Capacity. At the IBMB, I have continued my active training and mentoring of the next generation of scientists. This includes hosting 7 Erasmus+ students, directing 3 TFG and 8 TFM projects, and (co-)supervising 4 PhD theses (1 completed cum laude, 3 ongoing). Furthermore, I have contributed to the evaluation of 3 external PhD theses.
Research Productivity. I have so far published 48 peer-reviewed papers, 20 as (shared) first author and 7 as (co)corresponding, and held 4 competitive research fellowships. Moreover, 1 publication was just accepted at PLOS Pathogens (as co-corresponding author), while 2 others are under review (Preprint 1 & 2). My research coherently deals with topics of high biomedical or biotechnological relevance, ranging from bacterial pathogenicity factors (e.g., clostridial collagenases), proteolytic signatures in human cells (e.g., platelets), tissues (e.g., dental pulp), and murine cancer models (e.g., pancreas), enzyme development for celiac disease management (neprosin), and most recently, the functionalization of bacterial flagella and the use of protein design methods for BioTechMed. According to Google Scholar, I have an h-index of 27, >3300 citations, an i10-index of 40, and a cumulative impact factor of >400.
Publications
Munsamy, G., Illanes-Vicioso, R., Funcillo, S., Nakou, I. T., Lindner, S., Ayres, G., Sheehan, L. S., Moss, S., Eckhard, U., Lorenz, P., & Ferruz, N. (2024). Conditional language models enable the efficient design of proficient enzymes. https://doi.org/10.1101/2024.05.03.592223
Mizgalska, D., Rodríguez-Banqueri, A., Veillard, F., Książęk, M., Goulas, T., Guevara, T., Eckhard, U., Potempa, J., & Gomis-Rüth, F. X. (2024). Structural and functional insights into the C-terminal signal domain of the Bacteroidetes type-IX secretion system. Open Biology, 14(6). https://doi.org/10.1098/rsob.230448
Estevan-Morió, E., Ramírez-Larrota, J. S., Bushi, E., & Eckhard, U. (2024). Dissecting Cytophagalysin: Structural and Biochemical Studies of a Bacterial Pappalysin-Family Metallopeptidase. Biomolecules, 14(12), 1604. https://doi.org/10.3390/biom14121604
Rodríguez-Banqueri, A., Moliner-Culubret, M., Mendes, S. R., Guevara, T., Eckhard, U., & Gomis-Rüth, F. X. (2023). Structural insights into latency of the metallopeptidase ulilysin (lysargiNase) and its unexpected inhibition by a sulfonyl–fluoride inhibitor of serine peptidases. Dalton Transactions, 52(12), 3610–3622. https://doi.org/10.1039/d3dt00458a
Książek, M., Goulas, T., Mizgalska, D., Rodríguez-Banqueri, A., Eckhard, U., Veillard, F., Waligórska, I., Benedyk-Machaczka, M., Sochaj-Gregorczyk, A. M., Madej, M., Thøgersen, I. B., Enghild, J. J., Cuppari, A., Arolas, J. L., de Diego, I., López-Pelegrín, M., Garcia-Ferrer, I., Guevara, T., Dive, V., … Gomis-Rüth, F. X. (2023). A unique network of attack, defence and competence on the outer membrane of the periodontitis pathogen Tannerella forsythia. Chemical Science, 14(4), 869–888. https://doi.org/10.1039/d2sc04166a
Godoy-Gallardo, M., Merino-Gómez, M., Mateos-Timoneda, M. A., Eckhard, U., Gil, F. J., & Perez, R. A. (2023). Advanced Binary Guanosine and Guanosine 5’-Monophosphate Cell-Laden Hydrogels for Soft Tissue Reconstruction by 3D Bioprinting. ACS Applied Materials & Interfaces, 15(25), 29729–29742. https://doi.org/10.1021/acsami.2c23277
Alegre-Martí, A., Jiménez-Panizo, A., Martínez-Tébar, A., Poulard, C., Peralta-Moreno, M. N., Abella, M., Antón, R., Chiñas, M., Eckhard, U., Piulats, J. M., Rojas, A. M., Fernández-Recio, J., Rubio-Martínez, J., Le Romancer, M., Aytes, Á., Fuentes-Prior, P., & Estébanez-Perpiñá, E. (2023). A hotspot for posttranslational modifications on the androgen receptor dimer interface drives pathology and anti-androgen resistance. Science Advances, 9(11). https://doi.org/10.1126/sciadv.ade2175
Jimenez‐Alesanco, A., Eckhard, U., Asencio del Rio, M., Vega, S., Guevara, T., Velazquez‐Campoy, A., Gomis‐Rüth, F. X., & Abian, O. (2022). Repositioning small molecule drugs as allosteric inhibitors of the BFT‐3 toxin from enterotoxigenic Bacteroides fragilis. Protein Science, 31(10). Portico. https://doi.org/10.1002/pro.4427
Mendes, S. R., Eckhard, U., Rodríguez-Banqueri, A., Guevara, T., Czermak, P., Marcos, E., Vilcinskas, A., & Gomis-Rüth, F. X. (2022). An engineered protein-based submicromolar competitive inhibitor of the Staphylococcus aureus virulence factor aureolysin. Computational and Structural Biotechnology Journal, 20, 534–544. https://doi.org/10.1016/j.csbj.2022.01.001
Ramírez-Larrota, J. S., & Eckhard, U. (2022). An Introduction to Bacterial Biofilms and Their Proteases, and Their Roles in Host Infection and Immune Evasion. Biomolecules, 12(2), 306. https://doi.org/10.3390/biom12020306
del Amo-Maestro, L., Mendes, S. R., Rodríguez-Banqueri, A., Garzon-Flores, L., Girbal, M., Rodríguez-Lagunas, M. J., Guevara, T., Franch, À., Pérez-Cano, F. J., Eckhard, U., & Gomis-Rüth, F. X. (2022). Molecular and in vivo studies of a glutamate-class prolyl-endopeptidase for coeliac disease therapy. Nature Communications, 13(1). https://doi.org/10.1038/s41467-022-32215-1
Chidyausiku, T. M., Mendes, S. R., Klima, J. C., Nadal, M., Eckhard, U., Roel-Touris, J., Houliston, S., Guevara, T., Haddox, H. K., Moyer, A., Arrowsmith, C. H., Gomis-Rüth, F. X., Baker, D., & Marcos, E. (2022). De novo design of immunoglobulin-like domains. Nature Communications, 13(1). https://doi.org/10.1038/s41467-022-33004-6
Mizgalska, D., Goulas, T., Rodríguez-Banqueri, A., Veillard, F., Madej, M., Małecka, E., Szczesniak, K., Ksiazek, M., Widziołek, M., Guevara, T., Eckhard, U., Solà, M., Potempa, J., & Gomis-Rüth, F. X. (2021). Intermolecular latency regulates the essential C-terminal signal peptidase and sortase of the Porphyromonas gingivalis type-IX secretion system. Proceedings of the National Academy of Sciences, 118(40). https://doi.org/10.1073/pnas.2103573118
Eckhard, U., Körschgen, H., von Wiegen, N., Stöcker, W., & Gomis-Rüth, F. X. (2021). The crystal structure of a 250-kDa heterotetrameric particle explains inhibition of sheddase meprin β by endogenous fetuin-B. Proceedings of the National Academy of Sciences, 118(14). https://doi.org/10.1073/pnas.2023839118
Godoy-Gallardo, M., Eckhard, U., Delgado, L. M., de Roo Puente, Y. J. D., Hoyos-Nogués, M., Gil, F. J., & Perez, R. A. (2021). Antibacterial approaches in tissue engineering using metal ions and nanoparticles: From mechanisms to applications. Bioactive Materials, 6(12), 4470–4490. https://doi.org/10.1016/j.bioactmat.2021.04.033
Blöchl, C., Holzner, C., Luciano, M., Bauer, R., Horejs-Hoeck, J., Eckhard, U., Brandstetter, H., & Huber, C. G. (2021). Proteolytic Profiling of Streptococcal Pyrogenic Exotoxin B (SpeB) by Complementary HPLC-MS Approaches. International Journal of Molecular Sciences, 23(1), 412. https://doi.org/10.3390/ijms23010412
Eckhard, U., Blöchl, C., Jenkins, B. G. L., Mansfield, M. J., Huber, C. G., Doxey, A. C., & Brandstetter, H. (2020). Identification and characterization of the proteolytic flagellin from the common freshwater bacterium Hylemonella gracilis. Scientific Reports, 10(1). https://doi.org/10.1038/s41598-020-76010-8
Guo, X., Söderholm, A., Kanchugal P, S., Isaksen, G. V., Warsi, O., Eckhard, U., Trigüis, S., Gogoll, A., Jerlström-Hultqvist, J., Åqvist, J., Andersson, D. I., & Selmer, M. (2020). Structure and mechanism of a phage-encoded SAM lyase revises catalytic function of enzyme family. https://doi.org/10.1101/2020.08.16.253161
Gustafsson, R., Eckhard, U., Ye, W., Enbody, E., Pettersson, M., Jemth, P., Andersson, L., & Selmer, M. (2020). Structure and Characterization of Phosphoglucomutase 5 from Atlantic and Baltic Herring—An Inactive Enzyme with Intact Substrate Binding. Biomolecules, 10(12), 1631. https://doi.org/10.3390/biom10121631
King, S. L., Goth, C. K., Eckhard, U., Joshi, H. J., Haue, A. D., Vakhrushev, S. Y., Schjoldager, K. T., Overall, C. M., & Wandall, H. H. (2018). TAILS N-terminomics and proteomics reveal complex regulation of proteolytic cleavage by O-glycosylation. Journal of Biological Chemistry, 293(20), 7629–7644. https://doi.org/10.1074/jbc.ra118.001978
Jerlström Hultqvist, J., Warsi, O., Söderholm, A., Knopp, M., Eckhard, U., Vorontsov, E., Selmer, M., & Andersson, D. I. (2018). A bacteriophage enzyme induces bacterial metabolic perturbation that confers a novel promiscuous function. Nature Ecology & Evolution, 2(8), 1321–1330. https://doi.org/10.1038/s41559-018-0568-5
Dufour, A., Bellac, C. L., Eckhard, U., Solis, N., Klein, T., Kappelhoff, R., Fortelny, N., Jobin, P., Rozmus, J., Mark, J., Pavlidis, P., Dive, V., Barbour, S. J., & Overall, C. M. (2018). C-terminal truncation of IFN-γ inhibits proinflammatory macrophage responses and is deficient in autoimmune disease. Nature Communications, 9(1). https://doi.org/10.1038/s41467-018-04717-4
Tharmarajah, G., Eckhard, U., Jain, F., Marino, G., Prudova, A., Urtatiz, O., Fuchs, H., de Angelis, M. H., Overall, C. M., & Van Raamsdonk, C. D. (2018). Melanocyte development in the mouse tail epidermis requires the Adamts9 metalloproteinase. Pigment Cell & Melanoma Research, 31(6), 693–707. Portico. https://doi.org/10.1111/pcmr.12711
Butler, G. S., Connor, A. R., Sounni, N. E., Eckhard, U., Morrison, C. J., Noël, A., & Overall, C. M. (2017). Degradomic and yeast 2-hybrid inactive catalytic domain substrate trapping identifies new membrane-type 1 matrix metalloproteinase (MMP14) substrates: CCN3 (Nov) and CCN5 (WISP2). Matrix Biology, 59, 23–38. https://doi.org/10.1016/j.matbio.2016.07.006
Eckhard, U., Bandukwala, H., Mansfield, M. J., Marino, G., Cheng, J., Wallace, I., Holyoak, T., Charles, T. C., Austin, J., Overall, C. M., & Doxey, A. C. (2017). Discovery of a proteolytic flagellin family in diverse bacterial phyla that assembles enzymatically active flagella. Nature Communications, 8(1). https://doi.org/10.1038/s41467-017-00599-0
Abbey, S. R., Eckhard, U., Solis, N., Marino, G., Matthew, I., & Overall, C. M. (2017). The Human Odontoblast Cell Layer and Dental Pulp Proteomes and N-Terminomes. Journal of Dental Research, 97(3), 338–346. https://doi.org/10.1177/0022034517736054
Klein, T., Eckhard, U., Dufour, A., Solis, N., & Overall, C. M. (2017). Proteolytic Cleavage—Mechanisms, Function, and “Omic” Approaches for a Near-Ubiquitous Posttranslational Modification. Chemical Reviews, 118(3), 1137–1168. https://doi.org/10.1021/acs.chemrev.7b00120
Eckhard, U., Marino, G., Butler, G. S., & Overall, C. M. (2016). Positional proteomics in the era of the human proteome project on the doorstep of precision medicine. Biochimie, 122, 110–118. https://doi.org/10.1016/j.biochi.2015.10.018
Prudova, A., Gocheva, V., auf dem Keller, U., Eckhard, U., Olson, O. C., Akkari, L., Butler, G. S., Fortelny, N., Lange, P. F., Mark, J. C., Joyce, J. A., & Overall, C. M. (2016). TAILS N-Terminomics and Proteomics Show Protein Degradation Dominates over Proteolytic Processing by Cathepsins in Pancreatic Tumors. Cell Reports, 16(6), 1762–1773. https://doi.org/10.1016/j.celrep.2016.06.086
Eckhard, U., Huesgen, P. F., Schilling, O., Bellac, C. L., Butler, G. S., Cox, J. H., Dufour, A., Goebeler, V., Kappelhoff, R., Keller, U. auf dem, Klein, T., Lange, P. F., Marino, G., Morrison, C. J., Prudova, A., Rodriguez, D., Starr, A. E., Wang, Y., & Overall, C. M. (2016). Active site specificity profiling of the matrix metalloproteinase family: Proteomic identification of 4300 cleavage sites by nine MMPs explored with structural and synthetic peptide cleavage analyses. Matrix Biology, 49, 37–60. https://doi.org/10.1016/j.matbio.2015.09.003
Eckhard, U., Huesgen, P. F., Schilling, O., Bellac, C. L., Butler, G. S., Cox, J. H., Dufour, A., Goebeler, V., Kappelhoff, R., auf dem Keller, U., Klein, T., Lange, P. F., Marino, G., Morrison, C. J., Prudova, A., Rodriguez, D., Starr, A. E., Wang, Y., & Overall, C. M. (2016). Active site specificity profiling datasets of matrix metalloproteinases (MMPs) 1, 2, 3, 7, 8, 9, 12, 13 and 14. Data in Brief, 7, 299–310. https://doi.org/10.1016/j.dib.2016.02.036
Eckhard, U., Marino, G., Abbey, S. R., Tharmarajah, G., Matthew, I., & Overall, C. M. (2015). The Human Dental Pulp Proteome and N-Terminome: Levering the Unexplored Potential of Semitryptic Peptides Enriched by TAILS to Identify Missing Proteins in the Human Proteome Project in Underexplored Tissues. Journal of Proteome Research, 14(9), 3568–3582. https://doi.org/10.1021/acs.jproteome.5b00579
Eckhard, U., Marino, G., Abbey, S. R., Matthew, I., & Overall, C. M. (2015). TAILS N-terminomic and proteomic datasets of healthy human dental pulp. Data in Brief, 5, 542–548. https://doi.org/10.1016/j.dib.2015.10.003
Marino, G., Eckhard, U., & Overall, C. M. (2015). Protein Termini and Their Modifications Revealed by Positional Proteomics. ACS Chemical Biology, 10(8), 1754–1764. https://doi.org/10.1021/acschembio.5b00189
Eckhard, U., Huesgen, P. F., Brandstetter, H., & Overall, C. M. (2014). Proteomic protease specificity profiling of clostridial collagenases reveals their intrinsic nature as dedicated degraders of collagen. Journal of Proteomics, 100, 102–114. https://doi.org/10.1016/j.jprot.2013.10.004
Barré, O., Dufour, A., Eckhard, U., Kappelhoff, R., Béliveau, F., Leduc, R., & Overall, C. M. (2014). Cleavage Specificity Analysis of Six Type II Transmembrane Serine Proteases (TTSPs) Using PICS with Proteome-Derived Peptide Libraries. PLoS ONE, 9(9), e105984. https://doi.org/10.1371/journal.pone.0105984
Prudova, A., Serrano, K., Eckhard, U., Fortelny, N., Devine, D. V., & Overall, C. M. (2014). TAILS N-terminomics of human platelets reveals pervasive metalloproteinase-dependent proteolytic processing in storage. Blood, 124(26), e49–e60. https://doi.org/10.1182/blood-2014-04-569640
Huesgen, P. F., Lange, P. F., Rogers, L. D., Solis, N., Eckhard, U., Kleifeld, O., Goulas, T., Gomis-Rüth, F. X., & Overall, C. M. (2014). LysargiNase mirrors trypsin for protein C-terminal and methylation-site identification. Nature Methods, 12(1), 55–58. https://doi.org/10.1038/nmeth.3177
auf dem Keller, U., Prudova, A., Eckhard, U., Fingleton, B., & Overall, C. M. (2013). Systems-Level Analysis of Proteolytic Events in Increased Vascular Permeability and Complement Activation in Skin Inflammation. Science Signaling, 6(258). https://doi.org/10.1126/scisignal.2003512
Eckhard, U., Schönauer, E., & Brandstetter, H. (2013). Structural Basis for Activity Regulation and Substrate Preference of Clostridial Collagenases G, H, and T. Journal of Biological Chemistry, 288(28), 20184–20194. https://doi.org/10.1074/jbc.m112.448548
Marino, G., Huesgen, P. F., Eckhard, U., Overall, C. M., Schröder, W. P., & Funk, C. (2013). Family-wide characterization of matrix metalloproteinases from Arabidopsis thaliana reveals their distinct proteolytic activity and cleavage site specificity. Biochemical Journal, 457(2), 335–346. https://doi.org/10.1042/bj20130196
Kofler, S., Asam, C., Eckhard, U., Wallner, M., Ferreira, F., & Brandstetter, H. (2012). Crystallographically Mapped Ligand Binding Differs in High and Low IgE Binding Isoforms of Birch Pollen Allergen Bet v 1. Journal of Molecular Biology, 422(1), 109–123. https://doi.org/10.1016/j.jmb.2012.05.016
Eckhard, U., Schönauer, E., Nüss, D., & Brandstetter, H. (2011). Structure of collagenase G reveals a chew-and-digest mechanism of bacterial collagenolysis. Nature Structural & Molecular Biology, 18(10), 1109–1114. https://doi.org/10.1038/nsmb.2127
Eckhard, U., & Brandstetter, H. (2011). Polycystic kidney disease-like domains of clostridial collagenases and their role in collagen recruitment. Bchm, 392(11), 1039–1045. https://doi.org/10.1515/bc.2011.099
Ducka, P., Eckhard, U., Schönauer, E., Kofler, S., Gottschalk, G., Brandstetter, H., & Nüss, D. (2009). A universal strategy for high-yield production of soluble and functional clostridial collagenases in E. coli. Applied Microbiology and Biotechnology, 83(6), 1055–1065. https://doi.org/10.1007/s00253-009-1953-4
Eckhard, U., Nüss, D., Ducka, P., Schönauer, E., & Brandstetter, H. (2008). Crystallization and preliminary X-ray characterization of the catalytic domain of collagenase G fromClostridium histolyticum. Acta Crystallographica Section F Structural Biology and Crystallization Communications, 64(5), 419–421. https://doi.org/10.1107/s1744309108010476
Eckhard, U., Schönauer, E., Ducka, P., Briza, P., Nüss, D., & Brandstetter, H. (2008). Biochemical characterization of the catalytic domains of three different clostridial collagenases. Bchm, 390(1), 11–18. https://doi.org/10.1515/bc.2009.004
Research lines:
There are no lines of investigation associated with this user.