Research in my lab aims at understanding protein function on the basis of atomic structure determination using X-ray crystallography as the main tool. The current focal point is the elucidation of the structure of the nuclear pore complex, an elaborate macromolecular protein assembly that constitutes the only gateway into and out of the eukaryotic cell nucleus. We employ an integrative approach, combining structure determination with biochemical, biophysical and cell biological methods

The Nuclear Pore Complex

In eukaryotes, genes are transcribed from DNA into RNA in the nucleus, whereas proteins are synthesized in the cytoplasm. Therefore, traffic across the nuclear envelope membrane is heavy and fundamentally important for live of any eukaryotic organism. Our goal is to understand the mechanism of nucleo-cytoplasmic transport of proteins and RNA. Nuclear pore complexes (NPCs) are vast protein assemblies that form circular openings in the nuclear envelope and are the only known entry and exit site of the nucleus. Composed of multiple copies of roughly 30 different proteins, organized in distinct subcomplexes, the entire NPC constitutes one of the largest known protein assemblies in the cell (roughly 16 times the size of a ribosome). Our long-term objective is to elucidate the entire NPC structure in atomic detail. As a start, we are characterizing the subcomplexes from which the NPC is built and into which it disintegrates during the breakdown of the nuclear envelope when the cell divides. These subcomplexes are amenable to high-resolution crystallographic analysis. Resulting structures will allow for much more precise functional probing of nucleo-cytoplasmic transport than currently possible.