At the cutting edge of biomedical science and mathematical modelling, researchers at the University of Bonn are pioneering an innovative approach to understanding the immune defense mechanisms within the human lung. The recipients of the prestigious “Modelling for Life and Health” research prize—Argelander Professor Dr. Ana Ivonne Vazquez-Armendariz and Schlegel Professor Dr. Jan Hasenauer—are combining experimental biology with sophisticated computational models to investigate the enigmatic behavior of alveolar macrophages, the lung’s critical “scavenger cells.” Their interdisciplinary work, funded by a €100,000 award, stands at the nexus of mathematics, computer science, and medicine, promising new insights into pulmonary health and disease.
Alveolar macrophages are specialized immune cells tasked with maintaining the cleanliness and health of the lungs by engulfing and eliminating harmful pathogens such as bacteria and viruses. These scavenger cells arise from two distinct cellular sources: embryonic progenitors and bone marrow-derived monocytes during adulthood. While embryonic-derived macrophages are involved primarily in maintaining long-term tissue homeostasis, their bone marrow counterparts are more active in mounting inflammatory responses and repairing lung tissue following injury. Despite their recognized importance, the precise influence of the cells’ origins on their functional behavior within the pulmonary microenvironment has remained elusive.
To unravel these complexities, Vazquez-Armendariz and Hasenauer are developing novel mechanistic models that capture the dynamic movement patterns and interaction behaviors of alveolar macrophages. Central to their investigation is the question of whether these immune cells exhibit random, stochastic migration throughout the lung tissue or if they follow directed, chemotactic trajectories in response to environmental cues. Understanding these patterns is essential, as macrophage motility influences their efficacy in detecting and neutralizing pathogenic threats and orchestrating repair mechanisms.
Experimental data are being generated using pioneering lung organoid technology—a model system comprising three-dimensional miniaturized lung structures derived from stem cells. These organoids faithfully recapitulate key aspects of the lung’s architecture and physiology, enabling controlled laboratory studies of cellular processes that would be infeasible in vivo. By extracting alveolar macrophages from different developmental sources and introducing them into these organoids, the team is able to monitor and quantify cell behavior in a highly realistic, yet controllable, microenvironment.
Advanced imaging modalities form a critical part of this study, enabling high-resolution, live-cell tracking of macrophage trajectories within the organoid constructs. Techniques such as time-lapse confocal microscopy and fluorescent cell labeling allow the researchers to collect rich spatial-temporal datasets. These datasets then inform the parametrization and validation of their mathematical models, which utilize frameworks from stochastic processes, differential equations, and agent-based simulations to describe cell migration and interaction dynamics over time.
The mathematical modelling undertaken by Hasenauer, an expert in the life sciences and engineering, integrates experimental observations with computational algorithms to generate predictive simulations. These models help decipher how intrinsic cellular properties and extrinsic signals govern the functional heterogeneity of scavenger cells. Through iterative cycles of model refinement and experimental testing, this systems biology approach aims to bridge the quantitative gap between observed macrophage behaviors and underlying molecular mechanisms, offering a more holistic understanding of pulmonary immune surveillance.
Beyond advancing fundamental science, the implications of this research are far-reaching for clinical medicine. A clearer picture of alveolar macrophage dynamics could contribute to the development of novel therapeutic strategies for lung diseases characterized by chronic inflammation, such as chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis. Enhanced models of immune cell behavior may also improve our understanding of lung infections, including those caused by emerging respiratory viruses, thereby informing the design of targeted treatments or vaccines.
The collaborative ethos underpinning this project reflects the broader transdisciplinary research framework at the University of Bonn. The university’s Transdisciplinary Research Areas (TRAs) “Modelling” and “Life and Health” unite mathematicians, biologists, clinicians, and computer scientists in tackling complex biomedical questions. This synergy enables the fusion of traditional empirical methods with computational innovations, fostering breakthroughs at the intersection of disciplines—a necessary direction given the intricate nature of living systems and their myriad interacting components.
This joint initiative is exemplified by the creation of the “Modelling for Life and Health” prize itself, which seeks to incentivize researchers to combine mathematical rigor with biological insight. The prize recognizes projects that demonstrate scientific excellence, innovation, and the promise of collaborative research crossing disciplinary boundaries. The award to Vazquez-Armendariz and Hasenauer marks the second time this accolade has been presented, underscoring the growing importance of integrative approaches in life sciences research.
Dr. Ana Ivonne Vazquez-Armendariz brings to the project a rich background in clinical biochemistry, molecular medicine, and disease modeling. Having studied in Mexico and Germany, she has led research units focused on lung health and pioneered the use of organoid systems to mimic pulmonary diseases. Her work has been widely recognized by prestigious institutions including the American Thoracic Society, affirming her status as a leading figure in lung biology and regenerative medicine. Her ongoing contributions at the University of Bonn continue to push the boundaries of lung disease research using organoid and cellular modeling platforms.
Professor Jan Hasenauer complements this expertise with a strong foundation in technical cybernetics, engineering, and applied mathematics. Since his appointment at Bonn, he has steered projects that meld mathematics with life sciences, specializing in modelling complex biological systems. His role as a Schlegel Professor—an esteemed position within the German Excellence Strategy—complements his involvement in multiple research clusters, blending quantitative analysis with biomedical inquiry. His proficiency in computational methods bolsters the project’s capacity for generating robust, mechanistic insights into immune cell kinetics.
This research exemplifies the power of transdisciplinary collaboration to tackle pressing health challenges. By integrating state-of-the-art experimental systems with theoretical and computational modeling, the team is poised to unlock new dimensions in our understanding of lung immunity. Their findings promise to contribute not only to the academic discourse but also to translational approaches that enhance human health outcomes. As respiratory diseases remain a significant global health burden, such pioneering work fuels hope for improved diagnostics, therapeutics, and preventative strategies founded on a deep mechanistic knowledge of the body’s own cellular guardians.
In the longer term, this approach can serve as a template for similar investigations across other organs and immune cell populations, advancing a systems-level grasp of human physiology and pathology. The combined efforts at the University of Bonn highlight the transformative potential of aligning mathematical innovation with biological discovery, fostering a new era of medical science where computation and experimentation coalesce to decode complex living systems.
Subject of Research: Functions and migratory behavior of alveolar macrophages in the lung, integrating mathematical modeling and lung organoid experiments.
Article Title: Joint Prize-Winning Research at the University of Bonn Unveils New Insights into Lung Immune Cell Dynamics through Mathematical Modeling and Organoid Technology
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Image Credits: Photo by Volker Lannert / University of Bonn
Keywords: alveolar macrophages, lung immunity, mathematical modeling, organoids, pulmonary disease, transdisciplinary research, immune cell migration, systems biology, lung organoids, computational biology, inflammation, regenerative medicine
