Research interests

My group is interested in molecular mechanisms of mitosis using budding yeast as a model organism. One particular important research area is the organization of microtubules that segregate the chromosomes in mitosis by gamma-tubulin complexes. We identified and characterized with Spc98 and Spc97 the first interactors of gamma-tubulin (see Geissler et al. (1996), Knop et al. (1997) and Knop and Schiebel (1998)). Later it tured out that Spc98 and Spc97 are conserved proteins (named GCP2 and GCP2 or hSpc98 and hSpc97) that form in all eukaryotes complexes with gamma-tubulin. The small gamma-tubulin complex, consisting of two molecules of gamma-tubulin and one molecule of Spc98 and Spc97, is necessary and sufficient to organize microtubules in budding yeast. It seems that Spc98 and Spc97 interact with receptors at the centrosome (named Spc72 and Spc110) and by this means target the gamma-tubulin complex in dependence of the cell cycle to defines sites of the microtubule organizing center. gamma-Tubulin most likely directly interacts with tubulin and may provide a ring-like platform for the assembly of microtubules by tubulin. Despite extensive research over the past 10 years relatively little is known about the structure of the small gamma-tubulin complex, its cell cycle dependent modifications, the role of GTP binding to gamma-tubulin and most important, the molecular machanism of how gamma-tubulin initiates the de novo formation of microtubules. These outstanding and very important questions will be addressed in this project. The Exzellenzcluster CellNetwork will provide the enviroment that is needed to apply the interdisciplinary approaches required to solve the questions of this proposal.

 

Methods applied

The gamma-tubulin complex will be purified and analyzed by biochemical approaches. The structure of the yeast gamma-tubulin complex will be determined in collaboration with E. Conti, Martisnsried. gamma-Tubulin mutants defective in e.g. GTP-bining will be characterized (live cell imaging, EM, FRAP, microtubule dynamics). Modifications of the gamma-tubulin complex will be determined by mass spec. and the function analyzed.