Synthetic Approaches to Pattern Formation Across Scales


Event details

Date 28.02.2024
Hour 10:1511:15
Speaker Beatrice Ramm, Ph.D., Associate Research Scholar/CPBF Fellow, Center for the Physics of Biological Function, Princeton University, Princeton, NJ (USA)
Location Online
Category Conferences - Seminars
Event Language English
A hallmark of living systems is self-organized pattern formation: the partitioning of molecules and cells into distinct spatial domains with different functions. But self-organization phenomena giving rise to pattern formation exhibit complex behavior that cannot be predicted from their components, complicating their investigation. To overcome this challenge, my research employs bottom-up and mammalian synthetic biology approaches to quantitatively describe the molecular mechanisms and emergent properties of self-organizing systems. In this talk, I will first describe how I study the pattern formation of bacterial protein systems by using in vitro reconstitution on membranes. The first example is the Escherichia coli MinDE system, which positions the cell division site and has become a model for pattern formation because it self-organizes into traveling surface waves and other patterns when reconstituted. Using this technique, I discovered that MinDE can transport unrelated “cargo” molecules via nonspecific interactions, resulting in large-scale gradients of such molecules and even their sorting by size. The underlying mechanism of this transport is diffusiophoresis, the transport of colloidal particles in gradients of solutes, which may represent a more general transport mechanism in cells. More recently, we showed that two other proteins, the Legionella pneumophila effectors MavQ and SidP, also self-organize into dynamic patterns in vitro, suggesting that such systems are more abundant than previously thought. I will discuss how the MavQ/SidP system differs from MinDE. Finally, I will highlight recent steps to probe and build cell-cell communication circuits that underlie multicellular pattern formation. I focus on posttranslational circuits like the activation of the EGFR-ERK pathway via cell surface shedding of transmembrane proligands by proteases, which feature complex cellular responses such as traveling waves. While the relevant intracellular signaling pathways are well understood, we lack the tools to probe the extracellular processes. To this end, I have designed synthetic pro-ligands with various synthetic and natural domains that are cleaved off the cell surface with recombinant proteases and engineered a genetically encoded biosensor for extracellular protease activity, which will be employed to observe shedding dynamics.

I received my PhD in Biochemistry from the Ludwig Maximilian University of Munich. I am fascinated by spatiotemporal organization, a hallmark of all living systems, and how it arises from a mixture of biochemical and purely physical and mechanical factors. In my research so far I have worked towards the mechanistic understanding of intracellular protein reaction-diffusion systems and phase separation processes using experimental approaches such as in vitro reconstitution and single molecule techniques. In the future, I would like to pursue an interdisciplinary approach at the interface of biochemistry, synthetic biology and biophysics to understand spatiotemporal pattern formation across scales.

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