Research Groups

Structural Self-Organization of Membranous Organelles

During their lifetimes cells must split, repair, and remodel their membrane structures including numerous specialized membrane-bound microenvironments to meet cellular needs. While we know that membrane organization is essential for cellular life, we largely do not understand the underlying molecular mechanisms. This blind spot on our map of the human cell is due the lag of technical approaches able to cover the broad range of scales that molecules bridge to self-organize into membranous organelles. A central question of our research is “How do micron-spanning molecular patterns form and direct molecular activity with atomic precision?”

To address this question, we study how the human cell self-assembles the nucleus, the cells biggest organelle using novel integrated structural biology approaches. Only within a few minutes following every cell division, countless molecules find their place in space and time to reassemble the membrane coated structure that is 10.000 times bigger in diameter than each of its parts. This process – very much like assembling a tent from its tightly packed pieces – provides an example and great case study to dissect the unknown principles leading to Structural Self-Organization of Membranous Organelles. In particular we focus on:

  • Molecular Architecture: How do monomer-polymer and liquid-liquid phase transitions of nuclear membrane associated proteins govern nuclear assembly?
  • Molecular Scales and Switches: How do posttranslational modifications trigger the formation of micron-spanning patterns?
  • Membrane Remodeling: How do molecular condensates dynamically shape and fuse bio-membranes?
  • Toxic dysregulation: How do dysregulated membrane organelle self-assembly programs propagate toxicity and cause disease?



Figure 1: Biomolecular patterning across scales during the formation of membranous organelles. Left, membrane proteins form surprising micron-spanning patterns during nuclear envelope formation in the dividing cell. Middle Left, newly discovered biophysical properties including the condensation of proteins into liquid-like droplets along bio-polymers suggest structural flexibility during membranous organelle formation. Middle right, the assembly of structured molecular machines might translate flexible assemblies into defined molecular events with atomic precision, for example to shape and fuse membranes. Right, Cartoon summarizing a first integrative snapshot of how bio-membranes, bio-polymers, and biomolecular condensates self-organize as essential step to build a functional nucleus.

Philosophy: We believe that the best science is the result of a team effort. The world of the unknown is vast compared to our knowledge and it takes creativity to explore it. To do so we have to connect, work together and ignore the boundaries of disciplines. If you are enthusiastic about fundamental biological questions, interested in cutting edge interdisciplinary science, and collaborative, we might be a good match.

For collaborations, internships, PhD and Postdoc position contact: vonappenmpi-cbg.de

Methodological and technical expertise

  • Protein biochemistry and reconstitution in membranes to create controlled conditions
  • Cryo-Electron Tomography to study the structure of reconstituted protein assemblies in high detail and the ultra-structure of organelles in cells.
  • Biophysics to understand molecular behavior
  • Proteomics to explore protein interactions including quantitative cross-linking mass spectrometry, proximity labeling, and proteomics.
  • Live cell imaging to follow dynamics, localization, and to validate mechanistic models in vivo