Research interests
Research Unit Prof. Dr. Oliver Gruss
Head of Research Unit
Prof. Dr. Oliver Gruss
Cell Division Unit
Tel.: 0228-73-4258
Fax: 0228-73-4263
Curriculum
- Diploma: University of Regensburg (Biochemistry)
- Doctoral Studies: Ruprecht-Karls-Universität Heidelberg (Molecular Cell Biology)
- Postdoctoral Fellow: European Molecular Biology Laboratory (EMBL), Heidelberg
- Research Group Leader and non-permanent Professor: Zentrum für Molekulare Biologie der Universität Heidelberg
- Since 2015: Professor, Department of Genetics, University of Bonn
Research Interest
- Mechanisms and regulation of mitotic spindle formation
- Identification of novel mitotic regulators by differential quantitative analysis of microtubule proteoms
- Functions of novel mitotic regulators in spindle assembly, chromosome segregation, genome stability and cell differentiation
- Interdependence of cell differentiation and the microtubule cytoskeleton
Experimental Approach
- Ex vivo reconstitution of microtubule functions in lysates derived from Xenopus oocytes and blastomeres.
- Quantitative analysis of mitotic microtubule behavior, spindle assembly, spindle morphology and chromosome segregation by real time imaging in vitro, in cell free extracts, intact cells and Xenopus blastomeres.
- Functional analysis of novel microtubule regulators by immunodepletion/inhibition in cell free extracts and CRISPR/Cas9 knockouts in cells and developing Xenopus.
Research Summary
In every cell division, the mitotic spindle faithfully segregates sister chromatids and ensures equal distribution of the genetic information to the two arising daughter cells. The accuracy of spindle formation directly relates to genomic stability. Defects in spindle assembly will cause chromosome segregation defects and may ultimately lead to infertility or malignant cell transformation.
The spindle features a bipolar, highly dynamic microtubule array that forms after global rearrangement of the entire microtubule cytoskeleton at the onset of mitosis. The mitotic microtubule rearrangement marks one of the most complex and profound regulatory switches in cytoskeletal functions.
Research in our group aims at elucidating general principles of mitotic microtubule regulation, at identifying key effectors that carry out this regulation and at understanding the detailed molecular mechanisms of their mode of action.
Our research benefits from the high degree of conservation of the underlying mechanisms and molecules involved. We therefore combine findings from different model organisms to answer our questions. We are applying experiments in human tissue culture cells, cell free lysates from highly proliferative amphibian oocytes and in vitro reconstitutions using purified components. The observation of spindle morphology, microtubule dynamics and chromosome segregation in real time by cutting edge light microscopy techniques allows us to analyse functions of key regulators in spindle formation in detail. Specific molecular functions are addressed by siRNA knockdown in intact cells, CRISPR/Cas9 knockout in early developing frogs as well as immunodepletion or inhibition experiments in cell free lysates.
We have previously identified novel principles and key components in mitotic microtubule regulation using quantitative differential proteomics. The recently discovered that SSX2IP-WRAP73 complex, for instance, regulates balanced microtubule regulation from both spindle poles in mitosis.
In the future, we are going to analyse the molecular mode of action of this conserved protein complex in detail. Likewise, we will further characterise poorly understood novel regulators in spindle formation identified in our comprehensive proteomic screens. We are also aiming at testing novel functions of microtubule regulators in cell-cell communication, balanced cell division in developing tissues and cell differentiation and cell fate decisions in developing Xenopus as vertebrate model organism.
