Gerlich, Daniel

Bridging resolution gaps in the study of cell division

Research in the Gerlich laboratory focuses on the mechanisms that underlie faithful division of human cells. To obtain large volumes of high time-resolution information on cell division, we develop technology for live cell imaging-based RNAi screening and modeling of cellular phenotypes. Furthermore, to bridge resolution gaps in the spatial domain, we integrate super-resolution fluorescence microscopy, electron microscopy, and live-cell imaging into correlative imaging workflows.

Movie 1. Automated time-lapse microscopy. Live HeLa cells expressing fluorescent core histone 2B (red) and EGFP-alpha-tubulin (green) were imaged on an RNAi live cell array. 384 movies were captured simultaneously and merged for visual display.

Using our imaging tools and biochemical follow-up analysis, we investigate how chromosome segregation errors lead to genomic instability and how cells sense and respond to segregation errors. We further aim to understand how membrane- and cytoskeletal dynamics coordinately mediate the split of cells at the end of cytokinesis, and perform kinetic studies on regulatory networks underlying mitosis. Please find out more about the individual research projects on the pages of individual lab members.

Figure 1. Computational image analysis workflow in CellCognition. (A) Time series of a cell line expressing a chromatin marker. (B) Object detection, tracking, and classification of mitotic stages based on supervised machine learning. The colors correspond to the labels in (D). (C) Stage transition probabilities for learning of Hidden Markov model, which serves error correction of stage classifications. (D) Example trajectory of a cell progressing through mitosis. (E) Automated annotation of cell trajectories over time. 80 randomly selected trajectories (rows) over 40 time frames (columns) are displayed (time-lapse: 4.6 min). Colors refer to morphology classes as labeled in (B). Adapted from Held et al., Nature Methods 2010.

Selected publications

J. Guizetti, L. Schermelleh, J. Mantler, S. Maar, I. Poser, H. Leonhardt, T. Muller- Reichert, D. W. Gerlich. Cortical Constriction During Abscission Involves Helices of ESCRT-III–Dependent Filaments.
Science (2011) DOI:10.1126/science.1201730

P. Steigemann, M. Schmitz, C. Wurzenberger, J. Guizetti, M. Held, S. Maar, and D. W. Gerlich. Aurora B mediated abscission checkpoint protects against tetraploidization.
Cell (2009) 136(3): 473-84

M. H. A. Schmitz, M. Held, V. Janssens, J. R. A. Hutchins, O. Hudecz, E. Ivanova, J. Goris, L. Trinkle-Mulcahy, A. I. Lamond, I. Poser, A. A. Hyman, K. Mechtler, J.-M. Peters, and D. W. Gerlich. Live imaging RNAi screen identifies PP2A-B55α and Importin β1 as key mitotic exit regulators in human cells.
Nature Cell Biol (2010) 12(9): 886-93

M. Held, M. H. A. Schmitz, B. Fischer, T. Walter, B. Neumann, B. H. Olma, M. Peter, J. Ellenberg, and D. W. Gerlich. CellCognition: time-resolved phenotype annotation in high-throughput live cell imaging.
Nature Methods (2010) 7(9): 747-54