open_UMR

Aaron Beller

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Willkommen auf open_UMR!

Open_UMR ist ein digitales Repositorium: Ein fachübergreifendes Publikationsportal, das wissenschaftliche Textpublikationen, Ressourcen, Forschungsdaten und Software von Universitätsangehörigen der Philipps-Universität sammelt, verfügbar hält und im open access offen zugänglich macht. Im Sinne einer hohen Qualität sowie einer potentiellen Nachnutzbarkeit ist dieses Repositorium kuratiert.

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Open Access
Structural insights into the energy-converting methanogenic Mtr complex by Cryo-EM
(2026-07-23)
Reif-Trauttmansdorff, Tristan
;
Schuller, Jan Michael
;
Hochberg, Georg
Methanogenic archaea are the primary biological source of methane emissions, with current global emissions estimated at approximately ~0.5 Gt/year. Through methanogenesis, they catalyze the terminal step of organic matter degradation under strictly anaerobic conditions, occurring in environments such as soils, wetlands, rice paddies, marine and freshwater sediments, landfills, sewage and wastewater treatment systems, as well as the digestive tracts of ruminants and termites. A substantial fraction of global methane emissions is biogenic in origin, arising from these anaerobic microbial processes in both natural and anthropogenic systems, and contributing significantly to total anthropogenic methane emissions. Due to its substantially higher radiative efficiency and Global Warming Potential relative to carbon dioxide (CO₂), methane is a major contributor to contemporary climate change. More than a century of research on methanogenic archaea has established a detailed scientific framework for understanding their physiology and metabolism. In recent decades, the core pathway of methanogenesis has been extensively investigated. The enzymatic steps involved in the conversion of substrates to methane, the unique cofactors required, and the majority of the participating enzymes have been well characterized. Despite these advances, several knowledge gaps remain, particularly with regard to energy conservation mechanisms in methanogenesis. For example, the molecular details of how the exergonic methyl transfer from methyl-tetrahydromethanopterin (CH₃–H₄MPT) to coenzyme M (CoM) is coupled to sodium ion translocation remain unresolved. This reaction, catalyzed by the membrane-bound Mtr complex, represents the only energy conserving step in hydrogenotrophic methanogenesis and is essential in the major methanogenic pathways that utilize only one substrate. In this thesis, I present my work on the Mtr complex from the mesophilic, freshwater methanogen Methanosarcina mazei. By applying genetic tools in the native organism, one-step purification of the Mtr complex was enabled using a strep-tagged MtrE subunit, thereby isolating an intact complex. Cryo-EM of the complex purified under aerobic conditions yielded a full assembly, revealing its overall architecture. Unexpectedly, a small protein, termed MtrI, was bound at the membrane-embedded MtrCDE trimeric core. Mass spectrometry demonstrated that MtrI associates with the complex only upon exposure to oxygen and is absent under strictly anoxic conditions, suggesting a role as an oxygen-responsive binding factor. Subsequent cryo-EM analysis of the anaerobically purified complex revealed an unexpected metallocluster located within the cavity formed by the MtrCDE trimer, at the position previously occupied by MtrI. The geometry of this cluster closely resembles nitrogenase FeMo/FeV/FeFe cofactors and was modelled as an [Fe₈S₉C] L-type cluster. Its location adjacent to the coenzyme M binding site and the corrinoid, together with its close proximity to the conserved sodium binding site, suggests a direct role in the coupling of methyl transfer to sodium translocation. Distinct conformational states of the complex further reveal helical motions implying a putative sodium translocation pathway. Altogether, this thesis advances our understanding of the molecular mechanisms underlying energy conservation in methanogenic archaea.
Open Access
Continuous-flow stimulation for high-resolution temporal analysis of single-cell transcriptome data
(2026-06-18)
Nelson, Philipp P.
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Chung, Ho-Ryun
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Schumacher, Johannes
Since its first attempts more than 15 years ago, single-cell sequencing has become a powerful technique for the analyses of cellular behavior. Compared to classical bulk sequencing, a considerable advantage is the possibility to study cellular dynamics on single-cell level, for example in differentiation and signal transduction. For this, the cal-culation of pseudotime based on similarities in the expression profile between the ana-lyzed cells has become a frequently applied technique and can be used to visualize dy-namical processes in single-cell experiments. A prototypical and well-characterized intracellular signaling pathway in the immune response is the NF-κB signaling system. In this system, it was shown that stimulus speci-ficity of the immune response is encoded by dynamical features like peak amplitude, duration of the signal, or oscillation both on protein and mRNA level. However, in almost all recent single-cell time-series experiments with stimulated cells, multiple samples are taken at specific time points during the experiment and the trajectories in between are imputed. To not depend on mathematical predictions and to increase the temporal resolution of the analyses by real data, a continuum of cells with theoretically all possi-ble stimulation times would be required. So far, no experimental approach exists for the generation of such a sample. In this work, a new experimental setup to create such a continuum for single-cell sequencing was developed from scratch and termed µCONST (microfluidic continuous-flow stimulation). The well-described NF-κB signaling system was chosen due to its rele-vance in autoinflammatory diseases and autoimmune disorders. During the develop-ment of the µCONST setup, different approaches were tested and critical steps were optimized. Finally, using microfluidics, millions of THP-1 cells could be stimulated with TNF continuously for a total stimulation time of five hours. From these cells, a dataset with more than 18,000 cells and approximately 65,000 reads per cell could be generated after using the BD Rhapsody™ platform for encapsulation and barcoding. By fractionized sample collection and multiplexing during sequencing, information on real-time was available as reference for cellular pseudotime. Preliminary analyses showed promising findings and the potential for further investigations but also unspecific stimulus-independent effects requiring further explorations. A high degree of biological and technical noise as well as only slight transcriptional changes between the cells prevented the application of published algorithms for pseudotime analyses and prediction of temporal trajectories. By adaption of the estab-lished bioinformatic method in parallel with the development of new mathematical ap-proaches the full potential of the µCONST dataset could be exploited in future analyses. With this knowledge, the inherent dynamics of the NF-κB signaling system and also other pathways could be investigated in more detail compared to “classical” time-series ex-periments. This might broaden our understanding of transcriptional dynamics and would open the possibility for new therapeutic approaches against autoinflammatory diseases and autoimmune disorders.
Open Access
Using LLMs to Study Biases in Tax Policy
(2026-09-07)
Pellicer, Miquel
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Kuran, İbrahim
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Wegner, Eva
This paper proposes the use of LLMs to help code the progressivity of tax policies and thereby examine whether the tax policy-making process exhibits a bias towards the affluent. We construct a database that matches tax policy proposals in party manifestos to tax policies actually implemented, drawing on OECD Economic Surveys for Germany and the UK from the late 1990s to the 2020s. We code the progressivity of each tax pledge and each implemented tax policy using semi-automated methods. Our results suggest a post-electoral bias towards the affluent: The share of regressive tax policies is around 10pp larger among implemented policies than among those in the manifesto.
Open Access
EVH Regulatory Preparedness Strategy
Bekeredjian-Ding, Isabelle
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Kirsch-Stefan, Nadine
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Fröde, Rita
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Mentrup, David
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Pinnapireddy, Shashank R.
The European Vaccines Hub (EVH) serves as a coordinative platform for the development of pandemic vaccines and monoclonal antibodies (mAb). Its ambition is to support vaccine and antibody development across all stages, seamlessly leading to large-scale manufacturing and marketing authorization. To fulfill this objective, the EVH will follow its Vaccines Readiness Plan (VRP), which covers the relevant aspects from pathogen selection to pre-pandemic vaccine development and stress testing of the network. This document specifically addresses the EVH strategy for anticipation and preparation for challenges that might impede product development, manufacturing and marketing authorization in a pandemic.
Open Access
Investigations on the Reactions of Organic Semiconductors with Reactive Metals
(2026-06-18)
Schöniger, Maik
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Gottfried, J. Michael
;
Seubert, Andreas
The performance and functionality of (organic) electronic devices are largely determined by their interfaces. Therefore, research on their formation and modification, for example through chemical reactions at the metal/organic interface, is of crucial importance for the development of novel functional materials. Numerous studies on various organic and polymer layers have shown that penetration of metals into these layers can have positive effects on the performance but may also cause severe degradation of interfacial layers. Porphyrin and corrole complexes are characterized by their versatile chemical tunability and are therefore considered promising organic compounds for a wide range of applications. This thesis aims to investigate two representative compounds of these classes, 5,10,15,20-tetraphenylporphyrin (H2TPP) and 2,3,8,12,17,18-hexaethyl-7,13-dimethylcorrole (H3HEDMC), with respect to their interfacial reactivity with reactive metals such as calcium and lithium. X-Ray Photoelectron Spectroscopy (XPS) and Hard X-Ray Photoelectron Spectroscopy (HAXPES) were used to clarify whether reactions take place and to what extent the metals penetrate into the organic layers. Additionally, reaction depths from previous studies were reevaluated. In the context of the analysis of HAXPES data obtained with synchrotron radiation, the concept of effective attenuation lengths is presented and used for quantification of overlayer thicknesses and reaction depths. It can be regarded as an extension of the concept of inelastic mean free paths, which is usually used. In this context, principles of photoemission spectroscopy are explained and theoretical relative sensitivity factors for the HIKE endstation at the synchrotron radiation facility BESSY II in Berlin are calculated and compared with experimental results. Furthermore, the determination of overlayer thick- nesses with XPS and HAXPES is described and compared to established methods such as using quartz crystal microbalances.