Assembly and function of the cell division machinery
The Gerlich laboratory studies how cells reorganize their internal components during the cell cycle. We are particularly interested in the compartmentalization of the mitotic cytoplasm, the structure and biophysical properties of human chromosomes, and chromosome interactions with cytoskeleton and membranes.
Most cellular structures extensively reorganize during cell cycle progression. Upon mitotic entry, interphase organelles transiently acquire a form that can be mechanically segregated to the two nascent daughter cells. Organelles subsequently restore their interphase morphologies during mitotic exit. We aim to understand how large sets of diverse molecular components collectively 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 folded and intertwined path of its template. The two DNA copies subsequently move apart to form a pair of rod-shaped mitotic sister chromatids. Several key factors in this process have been identified, yet how their molecular activities give rise to the macroscopic shape 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 identified the protein Ki-67 to function as a biological surfactant that maintains mitotic chromosomes dispersed in the cytoplasmic phase (Figure 1). Using cell biological, biophysical, and in vitro reconstitution approaches, we aim to further dissect how soluble cellular components target to the phase boundary between cytoplasm and chromatin. With this, we aim to understand how chromosomes control the shape of the mitotic spindle and how they guide membranes to form a single nucleus 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.