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The roles of GTPases in biogenesis of the large ribosomal subunit
No full textRibosomes are ribonucleoprotein complexes responsible for protein synthesis, and their biogenesis is a complex, highly orchestrated process requiring a significant amount of energy and the coordinated action of all three RNA polymerases. Disruptions in ribosomal subunit assembly can lead to dysfunctional ribosomes, causing severe congenital diseases (ribosomopathies), and may also contribute to tumorigenesis. Formation of the ribosomal subunits is coordinated by trans-acting ribosome biogenesis factors (RBFs) that mediate ribosomal RNA (rRNA) modification, folding and processing, as well as the incorporation and positioning of ribosomal proteins (RPs). GTPases are among the RBFs that consume energy to drive structural rearrangements of pre-ribosomal particles, and several of these enzymes play important roles in assembly of the large subunit. Much knowledge on ribosome biogenesis comes from the yeast Saccharomyces cerevisiae, and despite the conservation of key aspects of the process across eukaryotes, many human RBFs, including GTPases, remain to be fully characterised. Recent structural studies of human pre-60S particles have identified GTPBP4, GNL3, and GNL2 on the particles, suggest roles for these GTPases in 60S assembly, but their precise functions have remained elusive. Furthermore, another putative GTPase, GNL3L is enriched in nucleoli, a major site of ribosome assembly, but potential contributions of this enzyme to subunit assembly have remained unclear.
This study focused on analysing the roles of GTPBP4, GNL2, GNL3 and GNL3L during large ribosomal subunit maturation. Proteomics analyses provide insights into the timing of recruitment of these proteins to pre-ribosomal particles and their subsequent release, as well as the influence of nucleotides on their pre-ribosome association. Analyses of pre-rRNA processing in cells expressing GTP binding and hydrolysis mutants allowed to differentiate between the requirement for the presence of these proteins and the importance of their nucleotide binding/catalytic activities. Protein-RNA crosslinking approaches were used to identify GNL3L binding sites on pre-ribosomes and map RNA contact sites on the GTPase. Expression of truncated versions of GNL3 and GNL3L allowed the contribution of individual domains to pre-ribosome association to be determined. Also, the importance of the GTPase activity of GNL3L for ribosome function was explored. Collectively, these data provide new insights into the functions of GTPBP4, GNL3, and GNL2 during assembly of the large ribosomal subunit in humans and support the involvement of an additional GTPase, GNL3L. These findings contribute to further understand the biogenesis of human cytosolic ribosomes and the roles of GTPases in this process.2026-02-1
Untersuchung von Komplikationen nach elektiven makulachirurgischen Eingriffen
No full textBackground: Pars plana vitrectomy is an established surgical procedure for the treatment of tractional maculopathies. Over the past decades, several technical innovations have been introduced into the technique.
Objective: The primary aim of this study was to determine the complication rate of pars plana vitrectomy over a ten-year period at University Medical Center Goettingen.
Methods: A retrospective analysis was conducted using patient data from University Medical Center Goetttingen between 2010 and 2019. From the dataset comprising all vitrectomies, cases requiring reoperation due to postoperative complications were extracted and evaluated.
Results: In total, 3,113 vitrectomies were performed during the study period. Of these, 54 cases (1,73%) required reoperation due to postoperative complications, most commonly retinal detachment (1,48%) and endophthalmitis (0,26%). The estimated complication rate declined significantly over the ten years (p < 0.05).
Conclusion: Pars plana vitrectomy demonstrates a relatively low complication rate in this cohort, with a statistically significant decreasing trend over the study period. These findings highlight the positive impact of technical advancements on patient outcomes and may guide further optimization of vitreoretinal surgery.2025-11-1
Untersuchung der Phagozytosefähigkeit humaner Vollblutleukozyten in Abhängigkeit von der Stimulation durch Gummi arabicum
No full textBackground: Gum arabic, a polysaccharide exudate from Acacia senegal (L.)Willdenow trees,
has already been used by African native people in natural medicine. Methods: Using whole-blood
samples from young (20–35 years) and older (>80 years) healthy volunteers (each group n = 10),
the effect of an aqueous solution of GA on phagocytosis of Escherichia coli was examined with a
gentamicin protection assay. Whole-blood samples of each volunteer were stimulated with GA and
as a control with CpG oligodeoxynucleotides (Toll-like receptor -9 agonists) for 2 h, then co-incubated
with E. coli for 30 min and thereafter treated with gentamicin for up to 240 min to kill extracellular
bacteria. Then, whole-blood cells were lysed with distilled water, and colony-forming units were
counted by quantitative plating. Cytokine enzyme-linked immunosorbent assay for the detection of
TNF-α and IL-6 was performed using the blood supernatant. Results: The GA concentration tested
(20 mg/mL) did not affect the viability of eukaryotic cells. Phagocytosis of E. coli by whole-blood
leukocytes derived from young (p = 0.008) and older (p = 0.004) healthy volunteers was increased
by 120.8% (young) and 39.2% (old) after stimulation with GA. In contrast, CpG only stimulated the
bacterial phagocytosis by cells derived from young volunteers (p = 0.004). Stimulation of whole
blood with GA increased the intracellular killing of E. coli in young (p = 0.045) and older volunteers
(p = 0.008) and induced a TNF-α release in whole blood collected from older volunteers but not from
younger ones (p = 0.008). Conclusions: These data encourage the isolation of active compounds of
GA and the initiation of clinical trials addressing the preventive effect of GA on bacterial infections.2025-11-2
Thermodynamics and Kinetics of Chemo-mechanical Energy Conversion
No full textUnderstanding the structure-dynamics-function linkage in biomolecular systems at a mechanistic and quantitative level is a fundamental challenge in contemporary biophysics. This thesis employs molecular dynamics (MD) simulations, Bayesian inference, and Markov modeling to address this challenge for two enzymatic systems of high biological and biomedical relevance: CRISPR/Cas13a and F1-ATPase.
In the first part of this thesis (Chapter 2), I investigated the conformational dynamics of CRISPR/Cas13a along its catalytic pathway. Cas13a is an RNA-guided endonuclease that has shown great potential in medical diagnostics and genetic therapy. Despite growing interest in its applications, a mechanistic understanding of its activation and catalysis remains elusive. Here, I combined all-atom molecular dynamics (MD) simulations with DEER/PELDOR spectroscopy data (provided by our collaborators) to characterize the structure and dynamics of Cas13a from the bacterium Leptotrichia buccalis in the four known binding states, including the apo state whose structure has not been experimentally resolved. Large-scale inter-domain rearrangements and increased structural flexibility of the apo state compared to the RNA-bound states were observed in the MD simulations. These predictions are qualitatively supported by the inter-residue distance distributions extracted from the DEER/PELDOR spectra, and suggest an RNA-induced ordering mechanism for Cas13a activation. However, quantitative discrepancies between the distance distributions predicted by the MD simulations and those extracted from the DEER/PELDOR spectra are present, to which a few factors might have contributed and require further investigation.
To accurately interpret the DEER/PELDOR spectra used in the Cas13a study, I implemented in the second part of this thesis (Chapter 3) a Bayesian approach for extracting distance distributions from those data. DEER/PELDOR spectroscopy measures an oscillatory time-domain signal that encodes the distribution of distances between a pair of spin centers introduced into the biomacromolecule. The state-of-the-art method for extracting the encoded distance distribution from a given DEER/PELDOR spectrum, based on Tikhonov regularization (TR), suffers from overfitting and lacks reliable uncertainty
estimation. To mitigate these issues, I implemented and tested a Bayesian approach. In benchmark tests against synthetic datasets and applications to experimental spectra of Cas13a, my Bayesian approach demonstrates general applicability, high robustness, and the capability to fully quantify uncertainties, thus complementing TR to enhance the reliability of structural interpretations based on DEER/PELDOR spectra.
The third part of this thesis (Chapter 4) addresses the catalytic mechanism of F1-ATPase. As the catalytic domain of ATP synthase, F1-ATPase is pivotal for mechano-chemical energy conversion in mitochondria. Despite wide acceptance of the rotary catalysis concept, a quantitative description of the thermodynamics and kinetics within the catalytic pathway of F1-ATPase remains elusive. Here we developed a minimal yet thermodynamically consistent Markov model for F1-ATPase that involves the relevant conformational and chemical degrees of freedom and reproduces all relevant experimental data. Within the generic construction of a Markov model considering discrete orientations of the γ-subunit and several conformations and nucleotide binding states of each individual β-subunit, we systematically evaluated over 14,000 model variants via exhaustive Bayesian search in the large parameter space of transition rates, cross-validation, and analysis of physical and
chemical restraints. Unexpectedly, we find that a fully functional minimal model requires four distinct β-subunit conformations. Further, our model reconciles the decade-long bi-site vs. tri-site controversy, clarifying that both pathways contribute depending on ATP concentration. Additionally, our model suggests a Brownian-ratchet-like mechanism that explains the observation that one ATP hydrolysis event can trigger larger than 120◦ rotations, thereby explaining seemingly over 100% chemo-mechanical coupling efficiency.
The projects presented in this thesis provide not only new insights into specific biological systems, but also generally applicable tools and frameworks. Particularly, I have extended the application of Bayesian inference to the analysis of DEER/PELDOR spectroscopy data, and to the parametrization of Markov models. Further, the methodology developed in
Chapter 2 combining MD simulations and DEER/PELDOR spectroscopy could be useful for studying protein conformational dynamics with structural details at atomic resolution. Finally, the theoretical framework established in Chapter 4 for Markov modeling and hypothesis testing could enable one to study many other molecular machines whose enzymatic mechanisms involve close coupling between conformational motions, substrate binding, and chemical reactions.2025-10-1
Quantitative Analysis of Ankle Joint Motion Restriction Caused by Ankle Orthoses in Real-Time MRI
No full textAkute Bandverletzungen des oberen Sprunggelenks stellen eine der häufigsten
muskuloskelettalen Verletzungen dar und führen oft zu anhaltenden Schmerzen oder
chronischen Instabilitäten. In der Therapie haben sich Sprunggelenksorthesen als Standard
etabliert. Das Ziel der durchgeführten Studie war daher, die Bewegungseinschränkung durch
Sprunggelenksorthesen im oberen Sprunggelenk mithilfe der Echtzeit-MRT zu untersuchen.
In der Echtzeit-MRT wurden der Bewegungsradius in sagittaler Ebene über die gesamte
Plantarflexion und Dorsalextension sowie der Bewegungsradius in coronarer Ebene über die
gesamte Inversion und Eversion gemessen. Hierfür wurden neun Probanden in die Studie
eingeschlossen, die die Bewegungen ohne Sprunggelenksorthese und bei Anlage der vier
Sprunggelenksorthesen Juzo Pro Malleo, Malleo TriStep, PushMed Knöchelbandage und
AIRCAST AIR-STIRRUP II durchführten. Anhand vordefinierter anatomischer Landmarken
wurde die Bewegungslimitation beim Tragen der Sprunggelenksorthesen ermittelt.
Ohne Sprunggelenksorthese wurde ein Bewegungsradius in sagittaler Ebene von maximaler
Plantarflexion bis maximaler Dorsalextension von 53° gemessen. Bei allen vier
Sprunggelenksorthesen wurde eine signifikante Bewegungslimitation in sagittaler Ebene
beobachtet. Der Bewegungsumfang ohne Sprunggelenksorthese in coronarer Ebene von der
maximalen Inversion bis zur maximalen Eversion betrug 6,9°. Bei keiner der getesteten
Sprunggelenksorthesen wurde eine signifikante Bewegungseinschränkung in coronarer Ebene
beobachtet. Weder Gewicht, Größe und BMI, noch die Bauweise der Sprunggelenksorthesen
zeigten einen signifikanten Einfluss auf die Bewegungseinschränkung.
Die Untersuchung kann durch Messungen im unteren Sprunggelenk ergänzt werden, um die
Auswirkungen von Sprunggelenksorthesen auf das gesamte Sprunggelenk besser
nachzuvollziehen. Gleichzeitig ist weitere Forschung notwendig, um das Verständnis der
Wirkungsweise von Sprunggelenksorthesen zu verbessern. Darüber hinaus eröffnet die
Bewegungsquantifizierung mit der Echtzeit-MRT auch an anderen Gelenken vielfältige
Anwendungsmöglichkeiten.Acute ligament injuries of the upper ankle joint represent one of the most common musculoskeletal injuries and frequently lead to persistent pain or chronic instability. In therapy, ankle orthoses have become a standard treatment option.
The aim of the present study was therefore to quantitatively assess the motion restriction of the upper ankle joint caused by different ankle orthoses using real-time magnetic resonance imaging (MRI).
In real-time MRI, the range of motion in the sagittal plane (from maximum plantarflexion to maximum dorsiflexion) and in the coronal plane (from maximum inversion to maximum eversion) was measured. Nine healthy volunteers were included in the study and performed these movements without an orthosis and with four different ankle orthoses applied: Juzo Pro Malleo, Malleo TriStep, PushMed Ankle Brace, and Aircast Air-Stirrup II. Motion limitation while wearing each orthosis was determined based on predefined anatomical landmarks.
Without an orthosis, the total sagittal range of motion from plantarflexion to dorsiflexion was 53°. All four ankle orthoses significantly restricted motion in the sagittal plane. The total coronal range of motion from inversion to eversion without an orthosis was 6.9°; however, none of the tested orthoses produced a significant limitation in the coronal plane. Neither body weight, height, nor BMI, nor the specific design of the orthoses had a significant influence on the degree of motion restriction.
Future studies should include measurements of the lower ankle joint to better understand the overall biomechanical effects of ankle orthoses. Further research is also needed to deepen the understanding of their mechanisms of action. Moreover, quantitative motion analysis using real-time MRI offers broad potential for application to other joints.2025-11-1
Studies on Testicular Development and Aging in the Common Marmoset (Callithrix jacchus) and the Establishment of Somatic Testicular Cell Lines
No full textThe phenomenon of reproductive ageing in women has been known for a long time and some aspects of this phenomenon are well understood. However, ageing effects in the testes were not recognized for a long time, as aged males can still produce offspring. Only in recent years more and more findings have been made on the male side that the mammalian testis also shows clear signs of ageing, which could also be relevant for the development and health of the offspring. These effects and findings are important for human reproductive medicine and family planning, as the age of fathers has increased significantly in recent decades, particularly in “western” societies. For example, the average age of men at the birth of a child in Germany rose by 3.7 years between 1991 and 2022. Studies on male reproductive ageing are therefore necessary from the epidemiological-psychological level down to the molecular level in order to better understand this phenomenon and assess its effects.
In the first part of the present study, the expression pattern of two factors in the testis of the common marmoset (Callithrix jacchus), which is a useful model for human testicular biology, was investigated: p16INK4a and NR2F1. For this purpose, (1) analyses were performed during three stages of postnatal testicular development and (2) studies of adult testes in four age groups.
p16INK4a is known as a tumor suppressor protein that plays an important role in cell cycle regulation. It is encoded by the CDKN2A gene. Via cyclin-dependent kinases, p16INK4a inhibits the phosphorylation of the retinoblastoma protein and represses the transition of the cell from G1 to S phase. However, its role in the primate testis has only been initially investigated and not in a cell-type- and development-specific manner. Here we show that p16INK4a is expressed in all developmental stages and age groups of the marmoset testis. The expression of p16INK4a was restricted to the tubular compartment. p16INK4a is first specifically detectable in immature germ cells in the neonatal testis, but then in the adult testis at the protein level only in Sertoli cells. Furthermore, the expression of p16INK4a in the adult testis was age-dependent, with the proportion of Sertoli cells expressing p16INK4a increasing significantly with age. However, this observation does not appear to apply to all primate species. In the common marmoset testis, however, p16INK4a shows a clear development- and age-dependent expression pattern.
NR2F1 belongs to the group of nuclear orphan receptors. Its known functions include the regulation of central nervous system development, including the visual pathway. However, the expression of NR2F1 in the mammalian testis is unknown at the protein level and during development and aging; only limited transcriptomic data are available. In newborn testes, NR2F1 is detectable in both the tubular compartment (germ cells) and the interstitial compartment (possibly immature Leydig cells). In juvenile marmosets, expression was mostly restricted to the tubular compartment (germ cells), but a few interstitial cells (possibly Leydig cells) were also stained. In adult testicular tissue, NR2F1 was specifically detectable in spermatogonia. It was shown that NR2F1 expression increases with age, but then decreases in the oldest testes of marmosets. In general, NR2F1 is a novel marker for spermatogonia in the adult testis of the marmoset.
In vivo studies in primates, including humans, are often neither ethically nor practically feasible. Therefore, cell-based in vitro models of testicular function play an important role in understanding at least some aspects of gonadal function. Here, immortalized cell lines (as opposed to primary cell cultures) can be a useful substitute for in vivo studies as well as an unlimited resource due to their long-term stability in cell culture and the fact that they do not require further animal invasive procedures. Therefore, in the second part of this thesis I have generated immortalized monoclonal cell lines from adult and juvenile Sertoli and Leydig cells of marmosets. Immunofluorescence and PCR analyses confirmed the identity of one juvenile and one adult immortalized Sertoli and Leydig monoclonal cell line. The identity of the generated cell lines was confirmed by transcriptome analysis for the juvenile Sertoli and both Leydig cell lines, whereas the identity of the adult Sertoli cell line could not be confirmed and the results rather point to a Leydig cell identity. Overall, to our knowledge for the first time, somatic cells from the testis of the marmoset could be immortalized and are available as a resource for future in vitro studies, e.g. for in vitro interaction studies with germ cells or germ cell-like cells.
Taken together, the results presented contribute to a better understanding of aspects of aging in the marmoset testis and provide a new resource for animal-free in vitro investigation of primate testicular function.2025-10-2
Electron-Heralded Parametric Photon Generation
No full textAktueller Forschung zufolge besitzen quantenmechanische Phänomene großes Potential, die moderne Technologie zu verbessern, zum Beispiel über die Erhöhung von Rechengeschwindigkeit und durch sichere Datenverschlüsselung. Die zugrunde liegenden technologischen Fortschritte beruhen auf der effizienten Erzeugung von speziell zugeschnittenen "quantenoptischen Zuständen", die typischerweise durch nichtlineare optische Effekte, oder Licht-Materie Wechselwirkung entstehen. Bemerkenswerterweise soll die direkte Streuung zwischen freien Elektronen und optischen Moden auch als eine Quelle dieser quantenoptischen Strahlung fungieren, bei der die Eigenschaften der generierten Photonen, wie die spektrale Verteilung, die Polarisation und die Zustandsstatistik, durch die Elektronenenergie und die Streugeometrie vorgegeben werden.
Diese kumulative Dissertation zeigt die Elektronen-induzierte Generation von nicht-klassischem Licht in einem Transmissionselektronenmikroskop durch direkte Streuung freier Elektronen an der optischen Mode eines Wellenleiters. Durch die Anpassung der Phasengeschwindigkeit der optischen Mode an die Geschwindigkeit der hochenergetischen Elektronen wird deren Interaktionswahrscheinlichkeit verbessert, was zu einer erheblichen Steigerung der Photonenausbeute führt. Die gestreuten Elektronen und erzeugten Photonen werden in Koinzidenz detektiert, wodurch ihre zeitliche und energetische Korrelation zutage tritt und unkorreliertes Rauschen unterdrückt wird. Dies ermöglicht die Demonstration von Elektron-Photon-Paarzuständen und eine ausführliche Analyse des Photonen-Erzeugungsprozesses, die in zwei Artikeln präsentiert werden. Die Kombination der Koinzidenz-Detektion mit einer Post-Selektion von inelastisch gestreuten Elektronen bei einem definierten Energieverlust ermöglicht schließlich die Detektion Elektron-angekündigter Photonenzahl-Zustände, die als quantenoptisch gelten. Darüber hinaus wird die Koinzidenzfilterung detektierter Elektronen und Photonen demonstriert, welche eine rauscharme und kontrastverstärkte Bildgebung optischer Moden ermöglicht.
Diese Ergebnisse, welche sich auf Elektronen-Photonen-Streuung auf Einzel-Teilchen Ebene stützen, versprechen effiziente Anwendungen in koinzidenzverbesserter Elektronenmikroskopie und ermöglichen zukünftige Forschung im Bereich der freie-Elektronen-Quantenoptik, wie bespielsweise die vielseitige Photonenzustands-Erzeugung, und die Elektron-Photon Verschränkung.Recent research on quantum phenomena has shown great potential to enhance modern technology by increasing computation speed and enabling secure data encryption. Its underlying technological advancements rely on the efficient generation of tailored "quantum optical states", typically generated through nonlinear optical effects, or the interaction of light and matter. Notably, direct scattering between free electrons and optical modes is also anticipated to serve as a source of such non-classical, or quantum light, in which the generated photon properties, such as the spectral distribution, polarization, and state statistics, are defined by the electron beam energy and the scattering geometry.
This cumulative thesis showcases the electron-induced generation of non-classical light in a transmission electron microscope through the direct scattering of free electrons with the optical mode of a waveguide. By matching the phase velocity of the optical mode to the velocity of the high-energy electrons, the single-electron interaction probability is significantly enhanced, resulting in a substantial increase in photon yield. The inelastically scattered electrons and generated photons are detected in coincidence, revealing their temporal and energetic correlation, while suppressing uncorrelated noise. This enables the demonstration of electron-photon pair states and a detailed analysis of the photon generation process, which is explored in two subsequent articles. By combining the coincidence detection scheme with post-selection on inelastically scattered electrons at a defined energy loss, electron-heralded photon number states can be detected, which are considered non-classical. Furthermore, coincidence-gating of detected electrons and photons is demonstrated to enable noise-reduced and contrast-enhanced photonic mode imaging.
These findings, which harness electron-photon scattering on a single-particle level, promise application in coincidence-enhanced electron microscopy and facilitate future free-electron quantum optics research, encompassing versatile photon state generation and electron-photon entanglement, a field with vast potential.2025-10-3
Classifying spaces for quasi-topological groups
No full textThis thesis provides a quick introduction into quasi-topological spaces, first introduced by Spanier. It then constructs notions of numerable principal G-bundles in the quasi-topological case and constructs a quasi-topological classifying space for a quasi-topological group.2025-10-3
In situ Structural Studies of α-Synuclein Fibrils
No full textProtein aggregation into amyloid fibrils is a hallmark of many human diseases, yet the structural principles that govern fibril organization and their physiological consequences remain incompletely understood. This thesis examined how amyloid fibrils fold, interact with their surroundings, and may be detected in material derived from patients.
The first project investigated cardiac amyloid fibrils (AL59) from a patient with systemic light chain amyloidosis. Cryo-electron tomography showed that AL59 amyloid fibrils are consistently decorated by the extracellular matrix protein collagen VI. Interestingly, collagen appeared to helically wrap around the fibrils, revealing a case of chirality transfer from amyloids to matrix components. This finding provides one of the clearest structural examples of how amyloids can impose order on their environment, raising broader questions about how fibril–matrix interactions contribute to tissue pathology.
The second project focused on the structural consequences of novel α-synuclein (aSyn) mutations, K58N and G14R, which were recently identified in patients with Parkinson’s disease (PD) and atypical parkinsonism. Single-particle cryo-electron microscopy (cryo-EM) showed that these variants alter the protofilament balance in distinct ways: while wild-type aSyn forms a mixture of single- and double-protofilament fibrils (1PF and 2PF, respectively), K58N stabilises a 2PF arrangement, whereas G14R exclusively forms 1PF fibrils. Notably, G14R fibrils closely resemble pathogenic folds observed in multiple system atrophy and juvenile-onset synucleinopathy, suggesting a structural link between sequence variation and disease phenotype. Together, these results illustrate how single amino acid changes can reweight the structural landscape of aSyn fibrils and bias them towards disease-associated folds.
The third project explored whether fibrillar aSyn can be detected ex vivo from living patients by analysing patient-derived biological material using negative-stain transmission electron microscopy and cryo-EM. Despite their low abundance, fibrillar structures were detected that bore morphological resemblance to recombinant aSyn fibrils. This proof-of-concept demonstrates that such samples could provide a minimally invasive route to access native aSyn aggregates in patients.
Together, these studies demonstrate the value of structural approaches for bridging the gap between recombinant fibrils, patient-derived material, and physiological context. They reveal how amyloids can shape their environment, how disease mutations bias structural ensembles, and how native fibrils might be sampled from living patients.2025-11-1
Empirical Findings and Design Approaches for the Use of Distributed Ledger Technologies in Supply Chains
No full textDie Komplexität moderner Lieferketten erfordert die Koordination und Kommunikation einer Vielzahl an Wertschöpfungspartnern und benötigt somit resiliente und transparente Systeme, um Störungen effektiv zu bewältigen und eine verlässliche Versorgung sicherzustellen. Diese Notwendigkeit wird angesichts von unvorhergesehenen Störungen wie Pandemien, geopolitischen Konflikten wie Kriegen oder ökoligischer Rahmenbedingungen noch verstärkt und erfordert widerstandsfähige, transparente und nachhaltige Wertschöpfungsnetzwerke, um sowohl regulatorische Anforderungen als auch gesellschaftliche Erwartungen zu erfüllen. Vor diesem Hintergrund bietet die Distributed-Ledger-Technologie (DLT) durch Eigenschaften wie Unveränderlichkeit, Transparenz und Automatisierung über Smart Contracts das Potential, Kommunikationsineffizienzen, mangelnde Nachvollziehbarkeit sowie Defizite bei der Compliance-Prüfung in SC überwinden zu können. Da es sich bei DLTs jedoch um eine Technologie handelt, die erst im Jahr 2008 mit der Bitcoin-Blockchain aufkam, ist das vorhandene Wissen zum DLT-Einsatz in Lieferketten in Forschung und Praxis zum aktuellen Zeitpunkt begrenzt. Die vorliegende Dissertation adressiert dies und leitet gestaltungsorientiertes Wissen für den Einsatz von DLTs in Lieferketten her. Eingangs zeigt eine Literatur-Analyse als Teil der Dissertation, dass die Forschung bislang eine Fokussierung auf sektorspezifische Prototypen und technische Konzepte aufweist, Dies führt dazu, dass generalisierbare Erkenntnisse, praxisorientierte Implementierungs¬strategien und systematische Governance-Überlegungen weitestgehend fehlen. Aufbauend auf diesen Erkenntnissen adressieren fünf komplementäre, im Rahmen der Dissertation durchgeführte Forschungsbeiträge diese identifizierten Forschungslücken. Hierfür werden zuerst sinnvolle Einsatzgebiete für eine DLT im SC-Kontext erfasst und anschließend Erfolgsfaktoren sowie Barrieren für die technologische sowie organisatorische Einführung formuliert. Diese Erkenntnisse werden u. a. aus der Literatur sowie gescheiterten Praxisprojekten wie TradeLens oder Serai erhoben. Abschließend erfolgen gestaltungsorientierte Studien, die einen Prototypen für Zollprozesse sowie eine Interviewstudie umfassen und die identifizierten Erkenntnisse der Dissertation in 19 Gestaltungsempfehlungen zur Einführung von DLTs in Lieferketten überführen. Diese umfassen hierbei nicht nur die technische Implementierung, sondern auch Gestaltungswissen für das Betriebsmodell einer DLT, da diese von mehreren Lieferkettenparteien gemeinsam betrieben und genutzt werden muss. Die Ergebnisse zeigen somit, dass erfolgreiche DLT-Anwendungen nicht allein von technischer Machbarkeit, sondern vor allem von Governance-Strukturen, Anreizmechanismen und regulatorischer Einbettung abhängen. Damit liefert die Arbeit sowohl theoretische Beiträge zur Weiterentwicklung bestehender Rahmenwerke als auch praxisorientierte Gestaltungsempfehlungen für die schrittweise Einführung dezentraler Systemarchitekturen in Lieferketten. Die Dissertation schließt mit einem Ausblick auf zukünftige Forschung, insbesondere der Integration von DLT mit Internet-of-Things- und Electronic-Data-Interchange-Systemen.Due to the complexity of modern supply chains (SCs), coordination and communication among numerous value-creation partners are required. This, in turn, necessitates resilient and transparent systems to manage disruptions and ensure the reliable provision of goods. Unforeseen disturbances such as pandemics, geopolitical conflicts like wars, or ecological constraints reinforce this need for solutions by requiring resilient, transparent, and sustainable value networks capable of meeting regulatory requirements and societal expectations. Against this background, Distributed Ledger Technology (DLT) can address communication inefficiencies, traceability gaps, and compliance challenges in SCs through its inherent properties such as immutability, transparency, and smart-contract automation. However, since DLT is a technology that emerged only in 2008 with the Bitcoin blockchain, existing knowledge on its application in SCs is limited in research and practice. This dissertation addresses this gap by deriving design-oriented expertise for deploying DLT in SCs. Initially, a literature review conducted as part of the dissertation demonstrates that existing research has focused predominantly on sector-specific prototypes and technical concepts. This resulted in a lack of generalizable insights, practice-oriented implementation strategies, and systematic governance considerations. Building on these findings, five complementary research contributions conducted within the dissertation address the identified research gaps. First, suitable application areas for DLT in the SC context were identified, followed by the formulation of success factors and technological and organizational adoption barriers. These insights are drawn, among other sources, from literature and failed practical projects such as TradeLens and Serai. Finally, design-oriented studies, which comprise a prototype for customs processes and an interview study, translated the dissertation’s findings into 19 design recommendations for implementing DLT in SCs. These recommendations encompass technical implementation and operational model considerations, given that a DLT must be jointly operated and utilized by multiple SC parties. The results demonstrate that successful DLT applications depend not solely on technical feasibility but on governance structures, incentive mechanisms, and regulatory embedding. Accordingly, this work provides both theoretical contributions for advancing existing frameworks and practical design recommendations for the incremental implementation of decentralized system architectures in SCs. The dissertation concludes with an outlook on future research, particularly the integration of DLT with Internet-of-Things and Electronic Data Interchange systems.2025-11-1