David Grunwald Lab

Research in the lab is related to the nuclear pore complex (NPC). The nuclear pore is a remarkable transport machine situated in the nuclear envelope of eukaryotic cells, regulating the exchange of matter, energy and information between nuclear and cytoplasmic compartments. While it is the only ‘all-transporter’ in the cell (a channel that transports any kind of cargo in both directions of the channel), transport is highly specific and regulated by secondary transport factors. The nuclear pore is also the largest known protein complex in the cell. Its structure has been intensively studied using various methods reaching from biochemistry and crystallography to (cryo-) electron microscopy and eventually light microscopy. A very stable central frame work provides robust transport functionality, even under harsh preparation conditions. This is one reason why the nuclear pore has been called the largest nano-machine in the cell. However, large amounts of nuclear pore components have rather low affinity to its central frame work and are lost easily during classical preparation procedures. This makes it virtually impossible to study the intact nuclear pore outside of the living cell. Interestingly, the highly symmetric structure of the central frame work presents a major road block to assembling its three dimensional composition based on structure data of sub-complexes. Furthermore, a number of studies have lately implicated the nuclear pore in several disease pathways putting the ‘gate keeper’ function of the pore in a larger context.

Understanding architecture and function of the nuclear pore have been the driving forces in the field since the first observation of nuclear pores in EM images in the 1950’s. During the last decade it was possible to add more and more dynamic information to the function of nuclear pores, forcing nucleocytoplasmic transport studies to take a lead in driving technology development for inner cellular single molecule observations. We are now at the urge to explore the dynamics of specific individual protein-protein interaction in cells. An application of major interest for the general cell-biology field and again the nuclear pore might very well be at the forefront of developing next generations’ technology for quantitative imaging in living cells.

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