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EXC 3094:  SCALE – SubCellular Architecture of LifE

Subject Area Basic Research in Biology and Medicine
Term since 2026
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 533751785
 
The human body is made up of trillions of cells. Each cell is densely packed with molecules. To perform a vast array of functions, cells are subdivided into specialized segments, such as the nucleus, which safeguards genetic information, or mitochondria, which serve as cellular power plants, each containing a dedicated subset of molecules. These molecules follow a complex choreography and exploit synergistic effects to form these segments in a process of cellular self-organization. Scientists have mapped the molecular content of cellular segments and described their microscopic layout, but it is more challenging to understand how exactly they are formed and dynamically reshaped. It is currently not possible to predict how subcellular architecture is altered upon cellular stress, for example in neurodegenerative diseases or aging, where nuclear proteins mis-localize and aggregate in the cytosol, or mitochondria exhibit an abnormal substructure. This knowledge gap is caused by limits in our experimental capabilities, scientific conceptualization and computational power. SCALE is a consortium of computational, structural, and cellular scientists that aims to address this challenge with the following central elements: We will develop experimental methods to simultaneously monitor the activity and precise localization of different molecule types inside of cells, and harness the digital twin concept, already successfully applied in climate modeling and urban planning, to model cellular segments. Specifically, we will build digital models of human cell segments in molecular detail and allow them to evolve in computer simulations in a virtual reality. These digital twins of cellular segments will become more sophisticated over time by continuously integrating more experimental data, and through innovative high-performance computing and machine learning approaches. Ultimately, they will capture the self-organization process of multiple types of molecules. Our vision is that the digital twins learn how to predict the layout of subcellular architecture, and also become an innovative platform for collaborative data management, sharing and publishing. SCALE will also generate simplified cellular models for teaching and societal outreach, and train the next generation of structural cell biologists. Our goal is that digital twins turn into a routine tool used to generate hypotheses and streamline experimental investigations, e.g. by virtually perturbing cellular behavior or by introducing clinically relevant mutations, and to communicate scientific discoveries. Thus, our efforts will transform the way we do science and benefit the scientific community and our society.
DFG Programme Clusters of Excellence (ExStra)
 
 

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