Beatrice Ramm

Synthetic biology approaches to pattern formation

Friedrich Miescher Laboratory
Faculty in: IMPRS

Vita

PhD at the MPI of Biochemistry, Martinsried, 2020
Postdoctoral Researcher, MPI of Biochemistry, Martinsried, 2020
Associate Research Scholar and Fellow of the Center for the Physics of Biological Function (CPBF), Princeton University, 2020-2024
Max Planck Research Group Leader at the FML (starting January 2025)

Research Interest

I am fascinated by spatiotemporal organization in biology and how it arises from a mixture of biochemical, 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 the compositionally simple bacterial protein systems to the elaborate multicellular patterns that form during development of higher organisms. But despite this emergent complexity and ubiquity across scales, pattern formation usually relies on similar concepts and mechanisms.

Our group contributes to the understanding of pattern formation in biology with an interdisciplinary approach that sits at the interface of biochemistry, biophysics and synthetic (developmental) biology. We rely on quantitative analysis, systematic probing, and precise perturbation, as well as curious and careful observation, with an open mind for the experimental outcome.

We currently focus on two different scales of pattern formation: we investigate (1) how minimal, prokaryotic protein systems generate spatiotemporal organization on the intracellular scale, and (2) how multicellular patterns in mammalian tissues arise from (extracellular) protein circuits.

Prokaryotic protein systems exhibit rather complex behavior despite their compositional simplicity (only a few proteins are involved). We have been using these systems to describe general biochemical and physical mechanisms of self-organization [1], reveal underlying design principles of pattern formation, and discover emergent properties like diffusiophoretic transport [2,3]. To study them, we employ biochemical in vitro reconstitution, or “bottom-up” synthetic biology: we use purified proteins and model membranes to recreate these cellular processes in the test tube. We can further control the reaction geometry with microfabrication and micropatterning techniques, i.e., by generating two-dimensional membrane patches or by encapsulating reactions in lipid vesicles or droplets. Together this gives us precise control over all reaction conditions and parameters and the ability to quantitatively analyse the system’s behaviour using biochemical assays and quantitative fluorescence microscopy. We are then able to discern what reaction components are necessary and/or sufficient for a given function and to build detailed mechanistic models, often in collaboration with theoretical groups.
To obtain a similar level of control over multicellular pattern formation as the one achieved in biochemical in vitro reconstitution, we use mammalian synthetic biology, protein and cell engineering, and optogenetics to deconstruct and rebuild the protein circuits underlying multicellular pattern formation [4]. We build and employ molecular tools such as optogenetic proteins, fluorescent biosensors, and genetic circuits to precisely control and probe cellular processes. We are currently especially intrigued by how extracellular and cell-surface proteases modulate a variety of different processes like extracellular matrix remodeling and growth factor release, which shape tissue form and function.

Fluorescence microscopy images of prokaryotic protein systems reconstituted in vitro. — Figure 1: Fluorescence microscopy images of prokaryotic protein systems reconstituted *in vitro*. Top row (first two on the left): MinD and MinE self-organize into traveling waves and quasi-stationary patterns on a supported lipid bilayer. Top row (last two on the right): MinDE self-organization leading to transport of cargo molecules via diffusiophoresis. Bottom row: Various structures formed by the *M. xanthus* PomXYZ system *in vitro*.

Figure 1: Fluorescence microscopy images of prokaryotic protein systems reconstituted *in vitro*. Top row (first two on the left): MinD and MinE self-organize into traveling waves and quasi-stationary patterns on a supported lipid bilayer. Top row (last two on the right): MinDE self-organization leading to transport of cargo molecules via diffusiophoresis. Bottom row: Various structures formed by the *M. xanthus* PomXYZ system *in vitro*.

Available PhD Projects

Selected Publications

Ramm B, Schumacher D, Harms A, Heermann T, Klos P, Müller F, Schwille P, Søgaard-Andersen L (2023) Biomolecular condensate drives polymerization and bundling of the bacterial tubulin FtsZ to regulate cell division. Nat Commun 14: 3825; https://doi.org/10.1038/s41467-023-39513-2
Ramm B, Goychuk A, Khmelinskaia A, Blumhardt P, Eto H, Ganzinger KA, Frey E, Schwille P (2021) A diffusiophoretic mechanism for ATP-driven transport without motor proteins. Nat Phys 17(7): 850-858; https://doi.org/10.1038/s41567-021-01213-3
Ramm B, Glock P, Mücksch J, Blumhardt P, García DA, Heymann M, Schwille P (2018) The MinDE system is a generic spatial cue for membrane protein distribution in vitro. Nat Commun 9(1): 3942 https://doi.org/10.1038/s41467-018-06310-1
McNamara H, Ramm B, Toettcher J (2023), Synthetic developmental biology: New tools to deconstruct and rebuild developmental systems, Semin Cell Dev Biol 141: 33-42; https://doi.org/10.1016/j.semcdb.2022.04.013