57. Heidelberger Physik Graduiertentage

MAKING WAVES IN A TEST TUBE — HOW TO RECONSTITUTE BIOLOGICAL SELF-ORGANIZATION

Beatrice Ramm

 A hallmark of living systems is self-organized pattern formation: the partitioning of molecules and cells into distinct spatial domains with different functions, far from equilibrium. Eye-catching examples span all scales, from bird flocks and the stripes and spots on the skin and fur of animals, through cells assembling into tissues, down to the proteins that transform a bag of molecules into an organized cell. Theory models this with reaction–diffusion systems exhibiting Turing patterns and traveling waves. However, many (membrane-bound) protein systems follow mass-conserving dynamics that differ from classical Turing mechanisms and raise new experimental and theoretical questions. In these lectures, I will introduce bottom-up synthetic biology as an approach to studying biological self-organization. Using purified proteins, artificial membranes, microfabricated environments, and quantitative microscopy, we can reconstitute minimal pattern-forming systems in vitro and directly test how molecular interactions give rise to collective dynamics. The course will center on comparing and contrasting two experimental model systems. The first is the E. coli MinDE system, a model for pattern formation whose self-organized surface waves we can characterize in detail, and which revealed an emergent property: MinDE transports unrelated cargo molecules via a nonspecific mechanism termed diffusiophoresis. The second is the Legionella pneumophila MavQ/SidP lipid kinase–phosphatase system, which, together with its substrate lipids, self-organizes into dynamic patterns in vitro. Along the way, I will introduce the relevant biological concepts and experimental techniques, including model membranes, protein purification and labeling, biochemical assays, microfabrication, quantitative fluorescence microscopy, and image analysis. We will close by discussing how the same bottom-up logic can be extended to living cells and tissues, using mammalian synthetic biology to observe, perturb, deconstruct, and (re)build self-organizing systems. No biology background is assumed.