Biology subjects

Konig, M.

Publications and source records attributed to Konig, M..

8 recordsLinked to original sources

bioRxiv2026

Ageing of the Upper Airway Epithelial Niche Limits Tissue-Resident T Cell Immunity

Respiratory tract infections are a major cause of morbidity and mortality among older adults worldwide. Yet, how ageing shapes protective immunity within the upper respiratory tract (URT) remains poorly understood. Here, we profiled the nasal immune landscape of young adults and older adults with and without frailty, using high-dimensional cytometry, proteomics, single-cell transcriptomics and T cell receptor (TCR) sequencing. Ageing was associated with a selective reduction of tissue-resident memory T (Trm) cells, independent of effector T cell numbers, inflammageing levels or frailty and was accompanied by a decline in T cell receptor repertoire stability. Trm cells from older adults also showed decreased steady-state IFN{gamma} expression, accompanied by reduced antiviral transcriptional programs in the mucosa. Mechanistically, in vitro PBMC-epithelium co-culture models revealed that older adults have a reduced capacity for Trm differentiation, which was associated with a diminished epithelial TGF-{beta} secretion, driven by reduced expression in ciliated epithelial cells. Together, these findings reveal that URT immunity deteriorates with age due to disrupted epithelial-immune crosstalk. This identifies the epithelial niche as a key regulator of mucosal immune ageing and suggests that enhancing TGF{beta} signaling may improve the effectiveness of mucosal airway vaccination strategies in older populations.

immunology↗

bioRxiv2026

TabularQual: A spreadsheet-based format for annotating and curating logical models in SBML-qual

Logical models are widely used to study regulatory and signaling systems, yet their reuse, annotation, and exchange across tools remain challenging. Although SBML Level 3 Qualitative Models (SBML-qual) provides a standard representation, its XML-based syntax is difficult to inspect and edit directly. Here we introduce TabularQual, a spreadsheet-based, community-driven representation for Boolean and multi-valued logical models, together with a bidirectional converter between spreadsheets and SBML-qual. The converter is accessible programmatically and via a web interface to support diverse user workflows. We further describe two integration strategies that enable existing modeling tools to operate with TabularQual, either through SBML-qual exchange or via direct support. Case studies using the Stress Knowledge Map and CaSQ demonstrate how this integration supports model construction, curation, and reuse. TabularQual provides a practical bridge between human-readable model representations and standardized executable formats, supporting reproducibility, interoperability, and community-driven model development.

systems biology↗

bioRxiv2025

FAIRification of computational models in biology

Computational models are essential for studying complex systems which, particularly in clinical settings, need to be quality-approved and transparent. To enhance the communication of a models features and capabilities, we propose an adaptation of the Findability, Accessibility, Interoperability and Reusability (FAIR) indicators published by the Research Data Alliance to assess models encoded in domain-specific standards, such as those established by COMBINE. The assessments guide FAIRification and add value to models.

systems biology↗

bioRxiv2024

FROG Analysis Ensures the Reproducibility of Genome Scale Metabolic Models

Genome-scale metabolic models (GEMs) and other constraint-based models (CBMs) play a pivotal role in understanding biological phenotypes and advancing research in areas like metabolic engineering, human disease modelling, drug discovery, and personalized medicine. Despite their growing application, a significant challenge remains in ensuring the reproducibility of GEMs, primarily due to inconsistent reporting and inadequate model documentation of model results. Addressing this gap, we introduce FROG analysis, a community-driven initiative aimed at standardizing reproducibility assessments of CBMs and GEMs. The FROG framework encompasses four key analyses--Flux variability, Reaction deletion, Objective function, and Gene deletion--to produce standardized, numerically reproducible FROG reports. These reports serve as reference datasets, enabling model evaluators, curators, and independent researchers to verify the reproducibility of GEMs systematically. BioModels, a leading repository of systems biology models, has integrated FROG analysis into its curation workflow, enhancing the reproducibility and reusability of submitted GEMs. In our study evaluating 65 GEM submissions from the community, approximately 40% reproduced without intervention, 28% requiring minor adjustments, and 32% needing input from authors. The standardization introduced by FROG analysis facilitated the detection and resolution of issues, ultimately leading to the successful reproduction of all models. By establishing a standardized and comprehensive approach to evaluating GEM reproducibility, FROG analysis significantly contributes to making CBMs and GEMs more transparent, reusable, and reliable for the broader scientific community.

systems biology↗

bioRxiv2023

Curvature-induced lipid sorting beyond the critical packing parameter

Over the last few decades, the spatial organization of biomembranes has received a lot of attention. With the fluid mosaic model, Singer and Nicolson proposed that biomembranes behave as two-dimensional fluids, allowing proteins and lipids to diffuse freely and thus react to external stimuli. Biological functionality and membrane organization are intricately linked to each other, however, how these organizations emerge is yet to be established. Here we use coarse-grained molecular dynamics simulations to explore the relationship between membrane shape and lateral organization at the nanoscale for a broad range of lipid mixtures. Our results illustrate that membrane curvature and lateral organization are intimately linked at the nanoscale and the relationship is much more complicated compared to the traditional views, in particular the lipid shape concept. Furthermore, we show that large membrane curvature can disrupt phase separation, line tension, and interleaflet coupling leading to non-intuitive lipid sorting. Our findings highlight how curvature-driven sorting can alter the phase behavior of lipid mixtures, which could be crucial for cellular functionality.

biophysics↗

bioRxiv2023

A Consensus Model of Glucose-Stimulated Insulin Secretion in the Pancreatic beta-Cell

The pancreas plays a critical role in maintaining glucose homeostasis through the secretion of hormones from the islets of Langerhans. Glucose-stimulated insulin secretion (GSIS) by the pancreatic {beta}-cell is the main mechanism for reducing elevated plasma glucose. Here we present a systematic modeling workflow for the development of kinetic pathway models using the Systems Biology Markup Language (SBML). Steps include retrieval of information from databases, curation of experimental and clinical data for model calibration and validation, integration of heterogeneous data including absolute and relative measurements, unit normalization, data normalization, and model annotation. An important factor was the reproducibility and exchangeability of the model, which allowed the use of various existing tools. The workflow was applied to construct the first consensus model of GSIS in the pancreatic {beta}-cell based on experimental and clinical data from 39 studies spanning 50 years of pancreatic, islet, and {beta}-cell research in humans, rats, mice, and cell lines. The model consists of detailed glycolysis and equations for insulin secretion coupled to cellular energy state (ATP/ADP ratio). Key findings of our work are that in GSIS there is a glucose-dependent increase in almost all intermediates of glycolysis. This increase in glycolytic metabolites is accompanied by an increase in energy metabolites, especially ATP and NADH. One of the few decreasing metabolites is ADP, which, in combination with the increase in ATP, results in a large increase in ATP/ADP ratios in the {beta}-cell with increasing glucose. Insulin secretion is dependent on ATP/ADP, resulting in glucose-stimulated insulin secretion. The observed glucose-dependent increase in glycolytic intermediates and the resulting change in ATP/ADP ratios and insulin secretion is a robust phenomenon observed across data sets, experimental systems and species. Model predictions of the glucose-dependent response of glycolytic intermediates and insulin secretion are in good agreement with experimental measurements. Our model predicts that factors affecting ATP consumption, ATP formation, hexokinase, phosphofructokinase, and ATP/ADP-dependent insulin secretion have a major effect on GSIS. In conclusion, we have developed and applied a systematic modeling workflow for pathway models that allowed us to gain insight into key mechanisms in GSIS in the pancreatic {beta}-cell.

systems biology↗

bioRxiv2022

Multiplexed measurement of binding- and neutralizing antibodies to SARS-CoV-2 variants in 12.000 post-vaccine sera

Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 sera. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.

immunology↗

bioRxiv2017

Tellurium Notebooks - An Environment for Dynamical Model Development, Reproducibility, and Reuse

The considerable difficulty encountered in reproducing the results of published dynamical models limits validation, exploration and reuse of this increasingly large biomedical research resource. To address this problem, we have developed Tellurium Notebook, a software system that facilitates building reproducible dynamical models and reusing models by 1) supporting the COMBINE archive format during model development for capturing model information in an exchangeable format and 2) enabling users to easily simulate and edit public COMBINE-compliant models from public repositories to facilitate studying model dynamics, variants and test cases. Tellurium Notebook, a Python-based Jupyter-like environment, is designed to seamlessly inter-operate with these community standards by automating conversion between COMBINE standards formulations and corresponding in-line, human-readable representations. Thus, Tellurium brings to systems biology the strategy used by other literate notebook systems such as Mathematica. These capabilities allow users to edit every aspect of the standards-compliant models and simulations, run the simulations in-line, and re-export to standard formats. We provide several use cases illustrating the advantages of our approach and how it allows development and reuse of models without requiring technical knowledge of standards. Adoption of Tellurium should accelerate model development, reproducibility and reuse.\n\nAuthor summaryThere is considerable value to systems and synthetic biology in creating reproducible models. An essential element of reproducibility is the use of community standards, an often challenging undertaking for modelers. This article describes Tellurium Notebook, a tool for developing dynamical models that provides an intuitive approach to building and reusing models built with community standards. Tellurium automates embedding human-readable representations of COMBINE archives in literate coding notebooks, bringing to systems biology this strategy central to other literate notebook systems such as Mathematica. We show that the ability to easily edit this human-readable representation enables users to test models under a variety of conditions, thereby providing a way to create, reuse, and modify standard-encoded models and simulations, regardless of the users level of technical knowledge of said standards.

systems biology↗