Erwin Schrödinger-Preis 2024

Daniel Gerlich wird für seine wissenschaftlichen Leistungen im Bereich Chromosomenbiologie, insbesondere für seine Beiträge zum Verständnis der Zellteilung und der Chromatinstruktur, ausgezeichnet.

The genetic information that dictates the form and function of any biological organism is encoded in linear DNA molecules, which can reach extraordinary lengths—up to several centimeters in humans. To ensure proper reading, duplication, and transport of this genetic material, these DNA molecules are packaged into chromosomes in a specific three-dimensional organization. Through an innovative combination of advanced microscopy, computer vision, machine learning, biophysics, biochemistry, and genomics, Daniel Gerlich and his team have uncovered fundamental principles governing the organization of chromosomes. Their groundbreaking research offers molecular insights into how genomes function within the physical constraints of cells and how genetic information is faithfully inherited by progeny, providing crucial perspectives on these vital processes.

For most of the time, chromosomes exist as a contiguous, decondensed chromatin mass within the cell nucleus, serving as a template for gene expression. When cells divide, however, the nucleus disassembles, and chromosomes undergo a striking transformation, condensing into spatially distinct, compact structures. These structures are then transported by the mitotic spindle—an assembly of fibers and motor proteins that ensures the accurate segregation of one genome copy into each daughter cell. While the morphological reorganization of chromosomes during division has been observed for over a century, the molecular mechanisms underlying chromosome individualization remained elusive.

Using a genetic screen powered by automated microscopy, computer vision, and machine learning, Daniel Gerlich's group identified a protein, Ki-67, that mediates chromosome separation. Their work demonstrated that Ki-67 forms repulsive, electrically charged molecular brushes on chromosome surfaces, facilitating independent chromosome movement by the mitotic spindle (Cuylen et al., Nature, 2016). This discovery introduced a novel concept in cellular organization, showing that Ki-67 behaves like a surfactants, similar to detergents, within the framework of liquid-liquid phase separation of chromatin. Furthermore, the group revealed that this repulsive Ki-67 layer forms specifically on chromosomes compacted by deacetylation, a single chemical modification, thereby enabling efficient spindle-mediated movement (Schneider et al., Nature, 2022).

Following division, the nucleus is reassembled from scratch. This complex process requires that individual chromosomes coalesce into a single mass while being enwrapped by membranes to form a unified nuclear compartment. Simultaneously, non-nuclear organelles and cytoplasmic components must be excluded. While prior research had identified regulators of nuclear membrane tethering to chromatin, the mechanism by which chromosomes coalesce into a single nucleus remained unknown. Daniel Gerlich's team discovered that during the final stages of division, chromosomes cluster densely, expelling organelles and cytoplasmic elements. This reorganization depends on the inactivation of Ki-67's molecular brush activity (Cuylen-Haering et al., Nature, 2020). Additionally, they identified a newly formed polymer network, built by the protein BAF, which encloses the chromosome set and guides the membranes to form a single nucleus rather than multiple smaller ones. This discovery is important for genomic integrity, as isolated nuclei formed on individual chromosomes often result in severe DNA damage and genomic fragmentation—hallmarks of cancer cells (Samwer et al., Cell, 2017). These transformative insights into nuclear assembly redefine fundamental biological principles and are poised to become textbook knowledge. 

One of the most intricate processes in proliferating cells is the reorganization of duplicated chromosomal DNA into separate entities, called sister chromatids. This step is crucial for accurately transporting sister chromatids to opposite daughter cells. Recently, Daniel Gerlich's team developed a groundbreaking technique combining chemical DNA labeling and high-throughput sequencing, allowing them to map, for the first time, the folding patterns of sister chromatids in the replicated human genome. They demonstrated how two opposing molecular activities determine sister chromatid conformation: one pool of cohesin protein complexes links the chromatids, while another pool separates them by dynamically extruding DNA loops at linkage sites (Mitter et al., Nature, 2020; Batty et al., EMBO J, 2023). This revolutionary methodology provides a powerful platform for studying topological interactions within and between sister chromatids, contributing to processes such as DNA replication, repair, and chromosome segregation—key directions for Daniel Gerlich's future research.

Der Preisträger

Daniel Wolfram Gerlich is a senior research group leader at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences. He earned his PhD in Biology summa cum laude in 2002 from the University of Heidelberg, following a diploma in Biology from the University of Freiburg, completed in 1998.

Daniel Gerlich's distinguished career includes serving as an Assistant Professor at ETH Zurich, Switzerland (2005–2012), and as a postdoctoral fellow at the European Molecular Biology Laboratory (EMBL) in Heidelberg (2002–2005). Since 2012, he has been leading a research group at IMBA, where his work focuses on the three-dimensional architecture of the genome, the biophysical properties of chromosomes, and the mechanisms of nuclear assembly after mitosis. 

Daniel Gerlich has received numerous honors throughout his career. He was elected to the Academia Europaea in 2022 and has been a member of EMBO (European Molecular Biology Organization) since 2017. In 2021, he was awarded the ERC Advanced Investigator Grant, among several other high-profile research grants. Daniel Gerlich contributes to the scientific community, serving on editorial boards and as a panel member for the European Research Council. His research has been extensively published in leading scientific journals such as Nature and Science.