Beatrice Ramm

136 Lewis Thomas Lab.

Princeton University

Washington Road

Princeton, NJ 08540

I am currently a fellow at the Center for the Physics of Biological function (CPBF) at Princeton University. Before coming to Princeton, I was a PhD student in the Department of Cellular and Molecular Biophysics at the Max Planck Institute of Biochemistry (MPIB) while enrolled in the Graduate School of Quantitative Biosciences Munich (QBM).

I am fascinated by spatiotemporal organization in biology and how it arises from a mixture of biochemical and physical and mechanical factors. Self-organization phenomena that give rise to biological pattern formation exhibit unexpected and complex behaviour often impossible to predict from the individual components. This can be observed across all scales of life, from compositionally simple bacterial systems reconstituted in vitro to the complex architecture of the eukaryotic cell, to the elaborate multicellular patterns that form during the development of higher organisms.

I contribute to our understanding of pattern formation in biology with an interdisciplinary approach at the interface of biochemistry, biophysics and synthetic biology. To this end I employ quantitative analysis, systematic probing and precise perturbation, as well as curious and careful observation with an open mind for the experimental outcome.

news

Jun 28, 2023	Our paper on how a protein condensate regulates cell division in bacteria is out now!

selected publications

to see a full list of my publications click here

16. Biomolecular condensate drives polymerization and bundling of the bacterial tubulin FtsZ to regulate cell division

Beatrice Ramm*†, Dominik Schumacher*†, Andrea Harms, and 5 more authors

Nature Communications 2023

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Cell division is spatiotemporally precisely regulated, but the underlying mechanisms are incompletely understood. In the social bacterium Myxococcus xanthus, the PomX/PomY/PomZ proteins form a single megadalton-sized complex that directly positions and stimulates cytokinetic ring formation by the tubulin homolog FtsZ. Here, we study the structure and mechanism of this complex in vitro and in vivo. We demonstrate that PomY forms liquid-like biomolecular condensates by phase separation, while PomX self-assembles into filaments generating a single large cellular structure. The PomX structure enriches PomY, thereby guaranteeing the formation of precisely one PomY condensate per cell through surface-assisted condensation. In vitro, PomY condensates selectively enrich FtsZ and nucleate GTP-dependent FtsZ polymerization and bundle FtsZ filaments, suggesting a cell division site positioning mechanism in which the single PomY condensate enriches FtsZ to guide FtsZ-ring formation and division. This mechanism shares features with microtubule nucleation by biomolecular condensates in eukaryotes, supporting this mechanism’s ancient origin. How cell division is regulated with spatiotemporal precision is not fully understood. Here the authors show that a bacterial protein undergoes phase separation through surface-assisted condensation to enrich the tubulin homolog FtsZ in M. xanthus cell division.
10. A diffusiophoretic mechanism for ATP-driven transport without motor proteins

Beatrice Ramm*, Andriy Goychuk*, Alena Khmelinskaia, and 5 more authors

Nature Physics 2021

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The healthy growth and maintenance of a biological system depends on the precise spatial organization of molecules within the cell through the dissipation of energy. Reaction–diffusion mechanisms can facilitate this organization, as can directional cargo transport orchestrated by motor proteins, by relying on specific protein interactions. However, transport of material through the cell can also be achieved by active processes based on non-specific, purely physical mechanisms, a phenomenon that remains poorly explored. Here, using a combined experimental and theoretical approach, we discover and describe a hidden function of the Escherichia coli MinDE protein system: in addition to forming dynamic patterns, this system accomplishes the directional active transport of functionally unrelated cargo on membranes. Remarkably, this mechanism enables the sorting of diffusive objects according to their effective size, as evidenced using modular DNA origami–streptavidin nanostructures. We show that the diffusive fluxes of MinDE and non-specific cargo couple via density-dependent friction. This non-specific process constitutes a diffusiophoretic mechanism, as yet unknown in a cell biology setting. This nonlinear coupling between diffusive fluxes could represent a generic physical mechanism for establishing intracellular organization. Protein oscillations linked to cell division in Escherichia coli are shown to localize unrelated molecules on the cell membrane via a diffusiophoretic mechanism, in which an effective friction fosters cargo transport along the fluxes set up by the proteins.
4. The MinDE system is a generic spatial cue for membrane protein distribution in vitro

Beatrice Ramm, Philipp Glock, Jonas Mücksch, and 4 more authors

Nature Communications 2018

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The E. coli MinCDE system has become a paradigmatic reaction–diffusion system in biology. The membrane-bound ATPase MinD and ATPase-activating protein MinE oscillate between the cell poles followed by MinC, thus positioning the main division protein FtsZ at midcell. Here we report that these energy-consuming MinDE oscillations may play a role beyond constraining MinC/FtsZ localization. Using an in vitro reconstitution assay, we show that MinDE self-organization can spatially regulate a variety of functionally completely unrelated membrane proteins into patterns and gradients. By concentration waves sweeping over the membrane, they induce a direct net transport of tightly membrane-attached molecules. That the MinDE system can spatiotemporally control a much larger set of proteins than previously known, may constitute a MinC-independent pathway to division site selection and chromosome segregation. Moreover, the here described phenomenon of active transport through a traveling diffusion barrier may point to a general mechanism of spatiotemporal regulation in cells.
2. High-Speed Atomic Force Microscopy Reveals the Inner Workings of the MinDE Protein Oscillator

Atsushi Miyagi*, Beatrice Ramm*, Petra Schwille, and 1 more author

Nano Letters 2018

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The MinDE protein system from E. coli has recently been identified as a minimal biological oscillator, based on two proteins only: The ATPase MinD and the ATPase activating protein MinE. In E. coli, the system works as the molecular ruler to place the divisome at midcell for cell division. Despite its compositional simplicity, the molecular mechanism leading to protein patterns and oscillations is still insufficiently understood. Here we used high-speed atomic force microscopy to analyze the mechanism of MinDE membrane association/dissociation dynamics on isolated membrane patches, down to the level of individual point oscillators. This nanoscale analysis shows that MinD association to and dissociation from the membrane are both highly cooperative but mechanistically different processes. We propose that they represent the two directions of a single allosteric switch leading to MinD filament formation and depolymerization. Association/dissociation are separated by rather long apparently silent periods. The membrane-associated period is characterized by MinD filament multivalent binding, avidity, while the dissociated period is defined by seeding of individual MinD. Analyzing association/dissociation kinetics with varying MinD and MinE concentrations and dependent on membrane patch size allowed us to disentangle the essential dynamic variables of the MinDE oscillation cycle.
1. Sequence-resolved free energy profiles of stress-bearing vimentin intermediate filaments

Beatrice Ramm*, Johannes Stigler*, Michael Hinczewski, and 4 more authors

Proceedings of the National Academy of Sciences 2014

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Intermediate filaments (IFs) are key to the mechanical strength of metazoan cells. Their basic building blocks are dimeric coiled coils mediating hierarchical assembly of the full-length filaments. Here we use single-molecule force spectroscopy by optical tweezers to assess the folding and stability of coil 2B of the model IF protein vimentin. The coiled coil was unzipped from its N and C termini. When pulling from the C terminus, we observed that the coiled coil was resistant to force owing to the high stability of the C-terminal region. Pulling from the N terminus revealed that the N-terminal half is considerably less stable. The mechanical pulling assay is a unique tool to study and control seed formation and structure propagation of the coiled coil. We then used rigorous theory-based deconvolution for a model-free extraction of the energy landscape and local stability profiles. The data obtained from the two distinct pulling directions complement each other and reveal a tripartite stability of the coiled coil: a labile N-terminal half, followed by a medium stability section and a highly stable region at the far C-terminal end. The different stability regions provide important insight into the mechanics of IF assembly.