Assembly and function of the cell division machinery

Dividing cells extensively reorganize their internal organelles to build a machinery for chromosome segregation and cytokinesis. Understanding how large numbers of molecular components self-organize to form higher-order structures like mitotic chromosomes, the mitotic spindle, and the actomyosin ring remains a major challenge. We use high-content screening, biophysical manipulations, and biochemical reconstitution to gain insights into the molecular mechanisms underlying morphogenesis and biomechanics of dividing cells.

  • Chromosome structure and biophysics

    Chromosomes dynamically reorganize during the cell cycle to support DNA replication and gene expression during interphase and to support their mechanical redistribution to daughter cells during mitosis. How DNA folds to form compact mitotic chromosomes with aligned rod-shaped sister chromatids is not well understood. We use Cas9-based in vivo genome labeling and chromosome engineering to gain insights into the principles underlying mitotic chromosome morphogenesis. We further investigate how chromosomes acquire mechanical properties required for their independent motility on the mitotic spindle. We found that the protein Ki-67 forms brush-like structures on the surface of mitotic chromosomes to disperse chromosomes in the mitotic cytoplasm similar to surface active agents (surfactants), which maintain particles or immiscible liquid droplets dispersed in solution. Our current research aims to generate synthetic surfactant-like proteins and to study their function in cellular phase separation processes.

    Self-organization of the mitotic cytoskeleton

    When cells progress through mitosis, the cytoskeleton completely reorganizes to drive chromosome segregation and cytokinesis. The molecular components of the mitotic cytoskeleton have been largely identified, yet their self-organization mechanisms remain poorly understood. We use advanced microscopy, including super-resolution fluorescence microscopy, lattice light-sheet microscopy, and fluorescence polarization microscopy, to elucidate ultrastructure and mechanical properties of the mitotic spindle, the contractile actomyosin ring, and the ESCRT-III filament system promoting cytokinetic abscission.

    Computer vision and machine learning

    Automated live-cell microscopy generates data of tremendous complexity. Our laboratory develops computer vision and machine learning methods for automated cell phenotyping, available as open-source software software CellCognition. We are currently integrating computer vision and machine learning methods with microscope automation software to establish fully self-contained experimental workflows for complex interactive perturbation experiments.




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