Ulrike Kutay is a Full Professor at the Institute of Biochemistry (IBC) of the ETH Zurich. Her research is centered on the structure, function, biogenesis and dynamics of the cell nucleus. Ulrike studied Biochemistry in Berlin. During her dissertation work (Berlin, Boston), she characterized integration of tail-anchored proteins into the ER membrane. As a postdoc in Heidelberg, Ulrike investigated the mechanism of nuclear transport and identified RanGTP-controlled exportins. As an independent researcher, her lab initially deciphered various nuclear transport pathways, such as nuclear import of histones, export of miRNAs and ribosomal subunits. Current research topics include the dynamics of the nuclear envelope during mitosis, the structure and function of linker of nucleo- and cytoskeleton (LINC) complexes, the sorting of membrane proteins to the inner nuclear membrane and ribosome synthesis in mammalian cells. The Kutay group is tightly embedded into the Swiss National Centre of Competence in Research ‘RNA biology and disease’. The work of the Kutay lab relies on a wide repertoire of approaches, ranging from biochemical reconstitution of cellular processes, imaging-based (screening) technologies to mathematical modeling.
Ulrike is an elected member of EMBO, the Leopoldina, the Academia Europaea and she has been awarded an ERC Advanced grant for her research on the nuclear envelope. Ulrike Kutay is a co-founder of the Zurich Molecular Life Science PhD program, and she serves in the advisory boards of other graduate schools in Europe. Ulrike Kutay actively participates in the mentoring of junior researchers and is a member of the ETH Women Professors Forum. At ETH, she takes major administrative responsibilities, for instance as a vice chair of IBC, as a presidential delegate for faculty recruitment, and as a member of the ETH Zurich Strategy Committee.
Nuclear envelope breakdown (NEBD) is a major event during the drastic intracellular reorganization in preparation of mammalian cells for division. Disassembly of the nucleus exploits the activity of protein kinases involved in mitotic entry and is supported by microtubule-dependent restructuring of the NE. In my talk, I will cover two different aspects of NEBD, namely disassembly of nuclear pore complexes (NPCs) and the removal of membranes from chromatin. To study NPC disintegration, we had previously established a visual in vitro assay relying on semi-permeabilized cells. Exploiting this system, we have reconstituted the initial steps of mitotic NPC disassembly using purified soluble factors. We could demonstrate that the combined action of multiple mitotic kinases is sufficient to drive mitotic NE permeabilization. We further showed that hyperphosphorylation of both the gate-keeper nucleoporin Nup98 and the central scaffold component Nup53 is required for timely NPC disassembly. Secondly, we have assessed the importance of membrane dissociation from chromatin for chromosome segregation and cell division. When cells were allowed to enter mitosis with NE membranes tethered to chromatin, we observed strong chromatin segregation defects leading to a complete failure in cytokinesis. Our findings bear important further implications, as impaired cell division is known to promote genomic instability and tumorigenesis. Further, our observations indicate that cells must take great care to dissociate interactions between inner nuclear membrane proteins and chromatin. Notably, the dissociation of NE–chromatin contacts in not limited to organisms undergoing open mitosis but rather a general feature accompanying spindle formation in all eukaryotes.