Alexander von Appen Group

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Mechanisms of nuclear self-assembly

Welcome to the von Appen lab, where we explore the mechanisms of nuclear self-assembly. The nucleus, the largest organelle in human cells, plays a crucial role in protecting, organizing, and regulating our genome. Despite its complexity, it undergoes remarkable dynamics during cell division: as the cell enters mitosis, nuclear organization dissolves, leading to the detachment of the nuclear membrane from chromatin. The nucleoplasm and cytoplasm merge into a single entity, while the spindle distributes chromosomes to form daughter cells. Following this "open" mitosis, the entire organelle reassembles within minutes, prompting the central question:

What molecular mechanisms drive nuclear self-assembly?

Since the earliest vertebrates roamed the Earth, every second, approximately 20 million nuclei self-assemble in our bodies. This staggering rate suggests that nuclei formation relies on robust, well-conserved mechanisms. Our lab seeks answers to key questions:

  • How does the nuclear membrane form around chromatin?

  • What processes govern nucleocytoplasmic segregation?

  • How is the lamina, a structural component of the nucleus, formed?

  • What mechanisms underlie spindle disassembly?

  • Is chromatin folded into specific states during nuclear self-assembly?

  • Can open mitosis be harnessed for cellular reprogramming?

  • Does multicellularity necessitate open mitosis?

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.

To tackle these questions, we integrate diverse approaches to capture the structure and dynamics of large molecular assemblies.

Our research holds significant relevance as the critical protein machineries involved in nuclear self-assembly are linked to various diseases, including cancer, heart disease, neurodegeneration, and progeria. However, the pathological mechanisms remain largely undefined.

In the von Appen lab we believe that the best science emerges from collaborative efforts. The vast realm of the unknown requires creativity and interdisciplinary collaboration to explore. If you share our enthusiasm for fundamental biological questions and are interested in cutting-edge interdisciplinary science, we might be a perfect match.

For collaborations, internships, PhD, and Postdoc positions, please contact us at: vonappen@mpi-cbg.de.