SCALE – SubCellular Architecture of LifE
The human body is made up of trillions of functionally specialized cells. Each cell is densely packed with molecules that carry out biochemical reactions, convert energy, transmit signals or enable cells to move on demand. To perform these astonishingly diverse functions, cells are divided into specialized compartments that locally concentrate subsets of molecules. This subcellular architecture emerges dynamically and is constantly rearranged to adapt to cellular needs and environmental conditions. It is formed by a complex choreography in which molecules self-organize using synergistic effects.
Scientists have identified and characterized the key players of subcellular architecture, e.g. molecules that form cellular powerplants called mitochondria or those that act in defense against bacterial infection. However, how the individual building blocks of subcellular architecture act in concert in the complex environment of a cell remains poorly understood. We do not even understand basic concepts, e.g. how cellular membranes fold into the intricate multi-layered architecture of mitochondria, or how they surround and isolate invading bacteria. It is impossible to predict how subcellular architecture is rearranged, e.g. during stress or disease. This is due to limitations in our experimental capabilities and scientific conceptualization. Until now, it has been difficult to observe individual molecules inside of cells in high spatial and temporal detail. As a result, self-organizing biological processes are often conceptualized as simplified two-dimensional flow charts.
The SCALE cluster has a recognized strength in advanced experimental analysis of cells, computational modelling and simulation of molecules, and the study of subcellular organization, such as energy conversion in mitochondria or in bacterial resistance. SCALE will build on this expertise to develop methods to visualize the building blocks of cells at work and to facilitate the computational integration of scientific data. We will create digital twins of cells that simulate specific cellular segments in molecular detail and in four dimensions, to aid both, scientific conceptualization and societal education. The digital twins will predict cellular behavior in silico and advance our understanding of e.g. how mitochondrial architecture is rearranged during human disease or aging. Ultimately, they should help to design novel architectural elements based on synthetic biology approaches. By creating simplified digital twins, SCALE will enable students and the general public to 'experience' the beauty of cells and to learn about their fascinating functions and structures. SCALE's strong commitment to the development of novel computational methods, open science, and training of the next generation of scientists will advance quantitative digital biology and benefit the scientific community.
How the bacterial envelope confers resistance to pathogenic bacteria?
How assembly of complexes of the respiratory chain remodel cristae in mitochondria?
How cell-cell interfaces remodel their barrier function at different environmental conditions?
How lipid and protein synthesis at the ER shapes organelle architecture?
Nuclear Pore Complex
How very large cargos are exported through the nuclear pore complex (NPC)?
Innovative tools for Next Generation Structural Biology.