Synthetic Structural Biology – 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.

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.

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.