The Synthetic Structural Biology Lab is headed by Ulrich Eckhard, a Ramon y Cajal Research Investigator (2022-2027) and Junior Group Leader at the IBMB-CSIC, and we welcome Erasmus+, Bachelor,l and Master students for working with us in the fields of Molecular Biochemistry, Synthetic Microbiology, and Structural Biotechnology. Please get in touch! Similarly, if you are interested in applying for competitive third-party funding for PhD and post-doc projects, please contact us.
Our group is dedicated to the understanding the structural basis of proteolytic flagellins, their biological role in biofilm remodeling and pathogenesis, and how they impact the life style of the respective bacteria. Likewise, we are interested in reprogramming naturally occurring structural flagellins to encode for enzymatic units, and to use these augmented bacteria for biotechnological applications.
More to come in the near future!
PROTEOLYTYC FLAGELLINS IN BIOFILM REMODELING AND PATHOGENICITY
(Lead by Ulrich Eckhard)
Bacterial flagella represent membrane-bound protein nanomachines that drive bacterial motility. Its flagellum is built by the self-polymerization of thousands of flagellin molecules, which are composed of two distinct domains: a highly conserved N- and C-terminal coiled-coil domain that forms the core of the filament, and a central hypervariable region (HVR) of high sequence diversity that builds the filament surface. In 2017, we identified a new class of flagellins which harbored a unique metallopeptidase domain within their HVR, and termed them proteolytic flagellins (Eckhard et al. 2017, Nature Communications). In C. haemolyticum, these flagellinolysins represent the second most abundant protein component of purified filaments, and we could show proteolytic activity for both recombinant protein and purified flagella. However, biochemical and structural information is scarce, and the biological role of flagellum-mediated proteolysis in both biofilm remodeling and pathogenicity is ill-defined.
FLAGELLAR DISPLAY IN BIOTECHNOLOGY
(Lead by Ulrich Eckhard)
The bacterial flagellum is a highly sophisticated organelle primarily evolved for motility and harbors a long filament consisting of up to 30,000 subunits of the proteinicious building block flagellin. We aim to modify naturally occurring structural flagellins, and augment them with enzymatic functions to create dedicated nanomachines for biotechnology.
Ulrich joined the IBMB-CSIC in 2019, supported by the Beatriu de Pinós COFUND program, and since fall 2022, he is a Ramon y Cajal Research Investigator and Junior Group Leader.
After his PhD with Prof. Hans Brandstetter at the University of Salzburg (2007–2011), where he focused on the enzymatic and structural characterization of bacterial collagenases, he joined the lab of Prof. Chris Overall at the University of British Columbia, funded by a post-doctoral fellowship from the Michael Smith Foundation for Health Research (MSFHR). In Vancouver, he mastered several proteomics-based techniques and critically contributed to many highly collaborative projects, including the profiling of various biomedically relevant protease families and elucidating proteolytic processing in health and disease. In 2016, he returned to Europe and joined the lab of Prof. Maria Selmer at Uppsala University to study enzyme promiscuity and protein evolution, including a highly active phage-encoded S-adenosyl methionine (SAM) lyase. Enabled by funding from the Peter and Traudl Engelhorn Foundation (PTES), he then returned to Salzburg to lead his independent project on flagella-embedded proteolysis. In October 2019, he joined the Proteolysis Lab of Prof. Xavier Gomis-Rüth, where he continued his research in structural biochemistry and where he is now developing his own research line at the interface of molecular biochemistry, synthetic microbiology, and structural biotechnology to develop functionalized flagellins for biomedicine and biotechnology.
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Eva graduated with a BSc in Biotechnology from the Polytechnic University of Valencia in summer 2022, and she is now pursuing a Master’s degree in Biomedical Research at Pompeu Fabra University in Barcelona. For her bachelor’s degree thesis, she joined the Genomic of Gene Expression Lab in the Institute for Integrative Systems Biology (I²SysBio) in Valencia, a joint center of the CSIC and the University of Valencia. At I²SysBio, Eva worked on the evaluation and improvement of quality control methods for long read-defined transcriptomes. Since January 2023, she has been working on her master’s thesis at the Department of Structural and Molecular Biology (DSMB) of the Molecular Biology Institute of Barcelona (IBMB-CSIC), where she is working on the structural biochemistry of extracellular bacterial proteases involved in collagen and extracellular matrix turnover. In February, she was awarded a “JAE Intro 2022” Fellowship, with which she will branch out to synthetic microbiology and the enzymatic functionalization of bacterial flagella.
Bryan graduated from the University of Virginia (UVA), Charlottesville, USA, in 2020 with a Bachelor’s degree in Biology, and is currently pursuing a master’s degree in Biomedical Research at the University of Pompeu Fabra, Barcelona, Spain. During his undergraduate studies, he participated in a bioinformatics project focusing on the structural characterization and 3D modeling of the protein Smoothened (Smo) from Xenopus laevis, a key transmembrane protein of the hedgehog signaling pathway. He also completed a case study at the UVA Orthopedic Sports Medicine Clinic, where he investigated the effects of partial tearing of the anterior serratus muscle using clinical data. Since January 2023, he has been working on his Master’s thesis at the Molecular Biology Institute of Barcelona (IBMB-CSIC), where he focuses on the functionalization of bacterial flagella using synthetic biology and hybrid flagellins.
Oriol is currently in his final year of his Bachelor’s degree in Biotechnology at the University of Barcelona, and he is now completing his TFG internship and thesis at the IBMB-CSIC. During the last four years, he has acquired extensive knowledge in various fields, such as microbiology, immunology, and the industrial scale-up of biotechnological processes. As part of a research internship at the Barcelona Biomedical Research Park (PRBB), Oriol worked on fetal alcohol syndrome using the zebrafish model to analyze the impact of ethanol on early development. Oriol’s main objective is to understand biological processes and harness them for biomedical and biotechnological applications, and he has a key interest in biomedical engineering. In his Bachelor’s Thesis project, Oriol will expand our Synthetic Flagellin Toolkit by engineering new hybrid flagellins and creating orthogonal “Golden Gate Assembly”-compatible expression plasmids, which will allow the co-display of up to three flagellin variants.
Enkela graduated from the University of West Attica, Greece, in 2022 with a degree in Biomedical Sciences While studying, she volunteered as a laboratory assistant at both a public hospital and a clinical chemistry research laboratory, gaining experience in various lab skills and diagnostic lab equipment operations, which allowed her to develop her skills in specimen analysis, immunology, molecular biology techniques, and quality assurance. As part of her academic pursuits, she then completed a thesis titled “Gene Therapy for Male Infertility,” which investigated the feasibility and effectiveness of gene therapy in treating male infertility. After completing her studies, Enkela further expanded her knowledge in specimen collection, analysis, and result interpretation through an additional work experience at a diagnostic laboratory. In February 2023, she joined the IBMB-CSIC Department of Structural and Molecular Biology for an Erasmus+ internship, and she is now working at the intersection of proteolytic enzymes and synthetic microbiology.
I graduated from the Autonomous University of Barcelona in 2021 with a BSc in Microbiology, and I am now pursuing an MSc in Biomedical Research at Pompeu Fabra University. During my Erasmus+ exchange at the University of Helsinki, I worked in the Laboratory of Structural Biology at the HiLFE Institute of Biotechnology. I focused on the recombinant production of antibodies in mammalian cells against the infamous SARS-CoV-2 spike protein. I also did an internship at UAB’s Systems Biology of Infection Laboratory, where I tested new antimicrobial peptides against a variety of antibiotic-resistant pathogens. I investigated the emergence of cross-tolerances and tested various heparin binding peptides as antibiotic substitutes. Moreover, I volunteered as an instructor for the global Tiny Earth® initiative, which aims to tackle antibiotic resistance by engaging high school students in antibiotic research. Currently, I am working on my master’s thesis at the Molecular Biology Institute of Barcelona (IBMB), where I am focusing on the recombinant production of a plant endopeptidase with remarkable sequence specificity and great potential for biomedicine and food industry applications.
I completed my Bachelor’s Degree in Biology at the University of Zagreb in 2019. For my Bachelor’s thesis I focused on the biochemical properties of byssus, a protein structure secreted by certain mussels. Its ability to adhere in wet conditions, as well as its firm and elastic structure, make it an intriguing topic for future biotechnological and biomedical research. In 2022, I received my Master’s Degree in Molecular Biology from the same university. My Master’s Thesis project focused on the efficiency of somatic embryogenesis in Arabidopsis thaliana DNA methylation mutants. I assessed the embryogenic potential and its dependence on a functional de novo DNA methylation pathway, and analyzed gene expression levels of various embryogenesis-related genes. I am now conducting an Erasmus+ research internship at the Molecular Biology Institute of Barcelona (IBMB-CSIC), where I am attempting to restore motility in an Escherichia coli strain lacking flaglla using plasmid-derived flagellins, as well as to develop hybrid flagella with enzymatic activity.
I finished my bachelor’s degree in Biomedical Engineering at the University Pompeu Fabra in 2021. During my final year project at the BCN MedTech research unit, I developed an algorithm to scale a 3D knee joint model to match the dimensions of a patient with osteoarthritis, a key step towards a personalized and patient-specific model. Throughout my studies, I participated in several projects related to health problems, including the development of interfaces, mobile applications, medical devices, and the modelling of disease progression. I also extended my knowledge in computational modelling during my internship at IDIBAPS, where I studied aortic coarctation and implemented technological solutions related to the acquisition, processing, and interpretation of physiological and clinical data. Finally, a research stay at the Synthetic Biology Group at the Barcelona Biomedical Research Park allowed me to combine my engineering background with microbiology, immunology, and cellular biology to optimize bacterial cellulose production. Currently, I am pursuing a master’s degree in Biomedical Research, and my project focuses on the identification and characterization of minimal metallopeptidases by structural biochemistry. These scaffolds can then be used to design and engineer application-specific activities with customized activity and specificity profiles.
I graduated with a BSc in Animal Biotechnology from the University Abdelmalek Essaâdi (UAE) in Tangier, Morocco, in 2020, and I am now enrolled in the Molecular Biotechnology master’s program at the University of Barcelona (UB). For my bachelor degree project, I worked on parasitic infections, specifically the pathology and epidemiology of cutaneous and visceral Leishmaniasis in Morocco. I focused on a variety of topics, including disease pathology, clinical data analysis, and the evaluation of cost-effective prevention methods based on sandfly vector eradication. I also completed several trainings and internships in a clinical microbiology laboratory, where I worked on various aspects of clinical diagnosis, such as the isolation and identification of STD causing bacteria. Since spring 2022, I have been working on my master thesis project at the IBMB-CSIC with the goal to replace the surface exposed domains of a structural flagellin with a proteolytic domain to create an E. coli strain with flagellum-embedded enzymatic capability.
I completed my bachelor’s degree in “Molecular Biomedicine” at the University of Applied Sciences in Cologne, Germany, in 2021, and I am now pursuing a master’s degree in “Medical Immunosciences and Infection” at University of Bonn, Germany. During my bachelor’s degree, I worked in a diagnostic laboratory in Cologne, first in their microbiology department and later, when the COVID-19 pandemic began, I was transferred to the molecular biology department to assist with their RT-qPCR pipeline. For my bachelor thesis, I joined a tumor immunology group at the University Hospital of Bonn, where I got extensive research training in mouse work, cell culture, and flow cytometry. In August 2022, I joined the IBMB-CSIC Department of Structural and Molecular Biology as an Erasmus+ student to work on the functionalization of bacterial flagella.
Emma Bloch, University of Montpellier, France. Master Program work placement, 6 months. 2020
Camilla Winkler, RWTH Aachen. Erasmus+ internship, 6 months. 2019
The crystal structure of a 250-kDa heterotetrameric particle explains inhibition of sheddase meprin β by endogenous fetuin-B.
Eckhard U*, Körschgen H*, von Wiegen N., Stöcker W, and Gomis-Rüth FX (2021).
Proc Natl Acad Sci USA, 118(14): e2023839118.
Discovery of a proteolytic flagellin family in diverse bacterial phyla that assembles enzymatically active flagella.
Eckhard U*, Bandukwala H*, Mansfield MJ*, Marino G, Cheng J, Wallace I, Holyoak T, Charles TC, Austin J, Overall CM, and Doxey AC (2017).
Nature Communications, 8(1):521.
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.
Eckhard U*, Huesgen PF*, Schilling O*, Bellac CL, Butler GS, Cox JH, Dufour A, Goebeler V, Kappelhoff R, Auf dem Keller U, Klein T, Lange PF, Marino G, Morrison CJ, Prudova A, Rodriguez D, Starr AE, Wang Y, and Overall CM (2016).
Matrix Biology, 49:37-60.
Structure of collagenase G reveals a chew-and-digest mechanism of bacterial collagenolysis.
Eckhard U, Schönauer E, Nüss D, and Brandstetter H (2011). Structure of collagenase G reveals a chew-and-digest mechanism of bacterial collagenolysis.
Nature Structural & Molecular Biology, 18:10, 1109-1114.
Please refer to PubMed for a full and up-to-date publication record. A detailed CV can be obtained here: 09/2021; 10/2022.
- Title: “Structural Biochemistry of Proteolytic Enzymes”
- Dates: from 01/09/2022 to 31/08/2027
- Principal Investigator: Ulrich Eckhard
Ayuda RYC2020-029773-I financiada por:
Title: “Redesigning bacterial flagella to harbor functional domains for biotechnology and biomedicine (Flagella 3.0)”
- Dates: from 01/09/2022 to 31/08/2025
- Principal Investigator: Ulrich Eckhard
Proyecto PID2021-128682OA-I00 financiado por:
Title: “Structural and Computational Biochemistry of Proteins (BIOSTROMP)”
- Consolidated Research Groups of Catalonia Grant, Generalitat of Catalonia.
- Reference: 2021SGR00423 (40,000 EUR)
- Dates: 2023-2025
- Coordinator: Prof. F. Xavier Gomis-Rüth
- Role: Co-PI (€10,000 EUR)
We welcome Bachelor and Master students for working on their theses in the fields of Molecular Biochemistry and Structural Biotechnology with us. Please contact Ulrich Eckhard (firstname.lastname@example.org) for more details or to arrange an interview.
For more information, please see here.