Aim of the Collaborative Research Center
Bacteria are ubiquitous and constitute more than 50% of the world’s biomass. They exist in a huge variety of evolutionarily distinct lineages and are of enormous ecological, medical and biotechnological importance. Many aspects of their biology, such as metabolism or gene expression, have been studied intensively and thus provided key insights into the basic concepts of life. However, although many of the components that constitute bacterial cells are known, it is incompletely understood how these components are organized in space and time such as to generate a functional cell that can adopt a defined shape, grow and divide in a controlled manner, position cellular appendages at defined sites, and undergo complex differentiation programs or life cycles.
It has been appreciated for several decades that proteins can be sorted to different subcompartments of bacterial cells, such as the membranes or the periplasmic space, but their distribution within each subcompartment was long thought to be homogeneous. However, in recent years, it has become clear that bacteria do not simply rely on random biochemical reactions and undirected Brownian motion of their constituents to sustain growth and proliferation but in fact organize their cellular contents with exquisite precision. In doing so, they deploy proteins and other macromolecules to defined locations within the cell, thereby confining enzymatic activities to specific subcellular regions or arranging cellular components in a manner that facilitates their transport or their duplication during cell growth and division. The inventory of spatially organized components that have been identified in bacteria continues to grow rapidly and includes proteins, chromosomal and plasmid DNA, RNA molecules, ribosomes, metabolites (such as lipids), storage granules, and the second messenger c-di-GMP. Importantly, the positioning of these components is highly dynamic and changes over time in response to internal or external cues. These dynamics constitute the basis for fundamental cellular processes such as cell growth, cell division, cell cycle regulation, cell differentiation, motility and signal transduction, thus touching on essentially every aspect of cellular function.
Importantly, current data indicate that the molecular mechanisms and factors that spatiotemporally organize bacterial cells have only little overlap with those identified in eukaryotic systems. For instance, the subcellular architecture of bacteria is generally established independently of membrane-bounded organelles, even though some bacterial species do possess specialized protein- or membrane-bounded microcompartments. Moreover, even for key regulatory factors that are conserved across the three domains of life, such as actin- and tubulin-like cytoskeletal elements, the cellular functions and mechanisms of action differ significantly. Therefore, most of the knowledge accumulated in the long-established field of eukaryotic cell biology is not directly applicable to bacteria. Nevertheless, despite this divergence at the molecular level, some of the overall organizing principles may be similar. Compared to eukaryotic cells, bacterial systems possess a relatively simple and streamlined architecture, which minimizes the number of components and interactions that need to be analyzed to clarify the functional mechanisms of individual regulatory modules. This reduced complexity makes bacteria ideal models to pinpoint fundamental principles that could underlie the organization of cells in all domains of life.
Despite the progress made in the field, our global understanding of cellular organization in bacteria is still limited, and the molecular mechanisms that underlie the function of spatiotemporally organized cellular systems are incompletely understood. This lack of knowledge is mostly due to technical limitations that have long impeded the resolution of structural details within the small dimensions of bacterial cells. However, recent advances in imaging technologies have now opened the door to visualizing the localization and dynamics of cellular components with exquisite precision and detail.
Building on this momentum, TRR 174 has established a comprehensive and highly coherent research program to investigate the molecular mechanisms controlling the spatiotemporal dynamics of bacterial cells. Its research is based on a broad and interdisciplinary approach that combines quantitative state-of-the-art live-cell imaging and biochemical analyses with mathematical modeling and synthetic biological approaches.
It has been appreciated for several decades that proteins can be sorted to different subcompartments of bacterial cells, such as the membranes or the periplasmic space, but their distribution within each subcompartment was long thought to be homogeneous. However, in recent years, it has become clear that bacteria do not simply rely on random biochemical reactions and undirected Brownian motion of their constituents to sustain growth and proliferation but in fact organize their cellular contents with exquisite precision. In doing so, they deploy proteins and other macromolecules to defined locations within the cell, thereby confining enzymatic activities to specific subcellular regions or arranging cellular components in a manner that facilitates their transport or their duplication during cell growth and division. The inventory of spatially organized components that have been identified in bacteria continues to grow rapidly and includes proteins, chromosomal and plasmid DNA, RNA molecules, ribosomes, metabolites (such as lipids), storage granules, and the second messenger c-di-GMP. Importantly, the positioning of these components is highly dynamic and changes over time in response to internal or external cues. These dynamics constitute the basis for fundamental cellular processes such as cell growth, cell division, cell cycle regulation, cell differentiation, motility and signal transduction, thus touching on essentially every aspect of cellular function.
Importantly, current data indicate that the molecular mechanisms and factors that spatiotemporally organize bacterial cells have only little overlap with those identified in eukaryotic systems. For instance, the subcellular architecture of bacteria is generally established independently of membrane-bounded organelles, even though some bacterial species do possess specialized protein- or membrane-bounded microcompartments. Moreover, even for key regulatory factors that are conserved across the three domains of life, such as actin- and tubulin-like cytoskeletal elements, the cellular functions and mechanisms of action differ significantly. Therefore, most of the knowledge accumulated in the long-established field of eukaryotic cell biology is not directly applicable to bacteria. Nevertheless, despite this divergence at the molecular level, some of the overall organizing principles may be similar. Compared to eukaryotic cells, bacterial systems possess a relatively simple and streamlined architecture, which minimizes the number of components and interactions that need to be analyzed to clarify the functional mechanisms of individual regulatory modules. This reduced complexity makes bacteria ideal models to pinpoint fundamental principles that could underlie the organization of cells in all domains of life.
Despite the progress made in the field, our global understanding of cellular organization in bacteria is still limited, and the molecular mechanisms that underlie the function of spatiotemporally organized cellular systems are incompletely understood. This lack of knowledge is mostly due to technical limitations that have long impeded the resolution of structural details within the small dimensions of bacterial cells. However, recent advances in imaging technologies have now opened the door to visualizing the localization and dynamics of cellular components with exquisite precision and detail.
Building on this momentum, TRR 174 has established a comprehensive and highly coherent research program to investigate the molecular mechanisms controlling the spatiotemporal dynamics of bacterial cells. Its research is based on a broad and interdisciplinary approach that combines quantitative state-of-the-art live-cell imaging and biochemical analyses with mathematical modeling and synthetic biological approaches.