Welcome to the Gerlich Lab
The Gerlich laboratory studies how human cells reorganize their internal components during the cell cycle to establish distinct functions at different stages. We are particularly interested in the compartmentalization of the mitotic cytoplasm, the structure and biophysical properties of chromosomes, and chromosome interactions with cytoskeleton and membranes.
Cells contain thousands of different molecular species, which form organelles of diverse shapes and functions. Cell organelles undergo dramatic and highly regulated changes during mitosis, including nuclear envelope breakdown, chromosome condensation, organelle segregation, and nuclear reassembly. Although these are classic phenomena, insight into the underlying mechanisms has remained elusive due to the difficulty to link molecular activities to macroscopic phenomena involving complex mixtures of components. Our interdisciplinary team builds on recent developments in microscopy, biophysical assays, and biochemical reconstitution to uncover the principles underlying the assembly of the cell division machinery during mitotic entry and the rebuilding of interphase cells during mitotic exit.
We aim to understand how large sets of diverse molecular components collectively build and reshape macroscopic cell structures through self-organization.
One of the most fascinating cellular reorganization processes is the chromosome cycle. During S-phase, a copy of each chromosomal DNA is directly synthesized along the highly intertwined path of its template. The two DNA copies subsequently fold into a pair of rod-shaped mitotic sister chromatids, which then move towards opposing spindle poles. Several key factors for mitotic chromosome formation have been identified, yet how their molecular activities give rise to the macroscopic shape and biophysical properties of mitotic chromosomes has remained mysterious. We use a combination of in vivo genome labelling and imaging approaches, CRISPR/Cas9-based genome engineering, and DNA-sequencing-based chromosome conformation capture techniques to gain insights into dynamic genome reorganization during the cell cycle.
Mitotic chromosomes are non-membrane-bounded organelles that are separated from the cytoplasm by regulated surface properties. Using high-content screening, we have discovered that mitotic chromosomes are dispersed in the cytoplasmic phase by a surfactant-like protein. We have also identified a protein that forms a network surrounding anaphase chromosomes to shape a single nucleus during mitotic exit. Using cell biological, biophysical, and in vitro reconstitution approaches, we aim to further dissect the phase boundary between cytoplasm and chromatin. We further aim to understand how chromosomes, the cytoskeleton, and membranes are coordinated to form functional interphase cells during mitotic exit.
Our interdisciplinary team uses state-of-the art cell biological, biophysical, biochemical, and computational technologies and is supported by 18 scientific core facilities. Learn more about our projects and how we approach science.
Many human diseases are associated with improper chromosome segregation or perturbed cell assembly after mitosis. The mechanistic insight we will gain into the fundamental properties of mitotic cells is anticipated to reveal potential targets for therapeutic intervention in these diseases. Moreover, the study of cellular reorganization during mitosis will shed light on general principles underlying organelle morphogenesis, with broad implications for other biological processes such as differentiation.
Samwer, M., Schneider, MWG., Hoefler, R., Schmalhorst, PS., Jude, JG., Zuber, J., Gerlich, DW. (2017). DNA Cross-Bridging Shapes a Single Nucleus from a Set of Mitotic Chromosomes. Cell. 170(5):956-972.e23
Mierzwa, BE., Chiaruttini, N., Redondo-Morata, L., von Filseck, JM., König, J., Larios, J., Poser, I., Müller-Reichert, T., Scheuring, S., Roux, A., Gerlich, DW. (2017). Dynamic subunit turnover in ESCRT-III assemblies is regulated by Vps4 to mediate membrane remodelling during cytokinesis. Nat Cell Biol. 19(7):787-798
Cuylen, S., Blaukopf, C., Politi, AZ., Müller-Reichert, T., Neumann, B., Poser, I., Ellenberg, J., Hyman, AA., Gerlich, DW. (2016). Ki-67 acts as a biological surfactant to disperse mitotic chromosomes. Nature. 535(7611):308-12