Stark, Holger, Prof. Dr.
Major Research Interests
The work in our group is focused on 3D structure determination of large macromolecular complexes by single particle electron cryomicroscopy (cryo-EM). In cryo-EM, thousands of electron microscopical images of a macromolecular complex are taken at low temperature in the electron microscope and are used to calculate a 3D reconstruction of the object by computational image processing. Electron microscopical images can be considered as almost ideal two-dimensional projection images, similar to images obtained by computer tomography in medical applications. However, in cryo-EM the relative orientation of the molecules is a priori unknown and must be determined by computational meansprior to calculating the 3D structure. Cryo-EM is the method of choice for 3D structure determination of macromolecular complexes that are difficult to purify in the amounts and quality that is required for crystallization (X-ray crystallography). Due to the low copy number of many functionally important macromolecular complexes in the cell, cryo- EM is very often the only available method to study the 3D structure of these large macromolecules. Work in our group concentrates on macromolecular complexes related to pre-mRNA splicing, translation and cell cycle regulation and on the development of new methods to improve sample preparation, imaging and computational image processing techniques.
Homepage Department/Research Group
Selected Recent Publications
- Grimm C, Chari A, Pelz JP, Kuper J, Kisker C, Diederichs K, Stark H, Schindelin H, Fischer U (2013) Structural Basis of Assembly Chaperone- Mediated snRNP Formation. Mol Cell 49(4):692-703
- Sander B, Golas MM, Lührmann R, Stark H (2010) An approach for de novo structure determination of dynamic molecular assemblies by electron cryomicroscopy. Structure 18: 667-676
- Fischer N, Konevega AL, Wintermeyer W, Rodnina MV, Stark H (2010) Ribosome dynamics and tRNA movement as visualized by time-resolved electron cryomicroscopy. Nature 466, 329-333
- Herzog F, Primorac I, Dube P, Lenart P, Sander B, Mechtler K, Stark H, Peters JM (2009) Structure of the anaphase-promoting complex/cyclosome interacting with a mitotic checkpoint complex. Science 323: 1477-1481
- Schmeisser M, Heisen BC, Luettich M, Busche B, Hauer F, Koske T, Knauber KH, Stark H (2009) Parallel, distributed and GPU computing technologies in single-particle electron microscopy. Acta Crystallogr D Biol Crystallogr 65(Pt 7): 659-71
- Wolf E, Kastner B, Deckert J, Merz C, Stark H, Luhrmann R (2009) Exon, intron and splice site locations in the spliceosomal B complex. EMBO J 28(15): 2283- 2292
- Lührmann R, Stark H (2009) Structural mapping of spliceosomes by electron microscopy. Curr Opin Struct Biol 19(1): 96-102
- Kastner B, Fischer N, Golas MM, Sander B, Dube P, Boehringer D, Hartmuth K, Deckert J, Hauer F, Wolf E, Uchtenhagen H, Urlaub H, Herzog F, Peters JM, Poerschke D, Lührmann R, Stark H (2008) GraFix: sample preparation for single-particle electron cryomicroscopy. Nat Methods 5, 53-55
- Chari A, Golas MM, Klingenhager M, Neuenkirchen N, Sander B, Englbrecht C, Sickmann A, Stark H, Fischer U (2008) An assembly chaperone collaborates with the SMN complex to generate spliceosomal SnRNPs. Cell 135(3): 497- 509