Team
Team manager: Erdel Fabian
Presentation
Inspired by the functional diversity among genetically identical cells, our research focuses on the question how cells can form and maintain cell type-specific chromatin patterns to interpret their genome in a particular way.
These patterns are observed at the biochemical level, in the form of chromatin states that are linked to distinct sets of histone modifications, and at the biophysical level, in the form of membrane-less subcompartments that contain folded chromatin domains. Our main model systems are cultured mammalian cells and purified mammalian proteins that we study in the test tube. We also use and actively develop fluorescence microscopy approaches for our research, including live-cell confocal microscopy and single-molecule TIRF assays combined with microfluidics.
Project 1
To understand how posttranslational histone modifications are associated with biological functions we introduce tunable histone-modifying enzymes into living cells and study their behavior. These enzymes are for example coupled to dCas9 so that they can be targeted to different genomic loci using different guide RNAs. One of our goals is to engineer circuits that consist of several of these enzymes, which act together to form complex functional modules like toggle switches or amplifiers. Based on such circuits we try to dissect the mechanisms underlying epigenetic phenomena.
Project 2
We use the single-molecule technique called “DNA curtains” to study the dynamic behavior of DNA molecules and their interaction partners in real-time. DNA curtains allow us to directly visualize and quantify protein binding to DNA and protein transport along the DNA, and to track changes of the DNA conformation and the mechanics of the DNA-protein assembly. Based on these readouts, we try to understand how different cellular proteins drive the partitioning of the genome into functionally distinct chromatin types and how this process is altered in disease.
Project 3
Phase separation has emerged as an organizing principle in nuclear organization. We study chromatin condensates in living cells and in vitro to understand how they are formed mechanistically, how they affect the mechanical properties of chromatin and the entire cell nucleus, and how they affect cellular function. To this end, we change the levels of disordered chromatin-associated proteins in living cells, and we reconstitute chromatin condensates in the test tube to study them with different types of light and electron microscopy.
– Muzzopappa F*, Erdel F*. (2024). Beyond equilibrium: Roles of RNAs in condensate control. Curr Opin Genet Dev, 91: 102304. doi: 10.1016/j.gde.2024.102304
– rnould C, Rocher V, Saur F, Bader A, Muzzopappa F, Collins S, Lesage E, Le Bozec B, Puget N, Clouaire T, Mangeat T, Mourad R, Ahituv N, Noordermeer D, Erdel F, Bushell M, Marnef A, Legube G*. (2023). Chromatin compartmentalization regulates the response to DNA damage. Nature, 623: 183-192. doi: 10.1038/s41586-023-06635-y
– Hertzog M, Erdel F*. (2023). The Material Properties of the Cell Nucleus: A Matter of Scale. Cells, 12: 1958. doi: 10.3390/cells12151958
– Dolde U§, Muzzopappa F§, Neveu J, Erdel F*, Vert G*. (2023). LEAFY homeostasis is regulated via ubiquitin-dependent degradation and sequestration in cytoplasmic condensates. iScience 26: 106880. doi: 10.1016/j.isci.2023.106880
– Muzzopappa F, Hummert J, Anfossi M, Tashev SA, Herten DP, Erdel F*. (2022). Detecting and quantifying liquid-liquid phase separation in living cells by model-free calibrated half-bleaching. Nat Commun 13: 7787. doi: 10.1038/s41467-022-35430-y
– Muzzopappa F, Hertzog M, Erdel F*. (2021). DNA length tunes the fluidity of DNA-based condensates. Biophys J 20: 1288-1300. doi: 10.1016/j.bpj.2021.02.027
– Erdel F*, Rademacher A, Vlijm R, Tünnermann J, Frank L, Weinmann R,
Schweigert E, Yserentant K, Hummert J, Bauer C, Schumacher S, Al Alwash A, Normand C, Herten DP, Engelhardt J, Rippe K*. (2020). Mouse Heterochromatin Adopts Digital Compaction States without Showing Hallmarks of HP1-Driven Liquid-Liquid Phase Separation. Mol Cell 78: 236-49.e7. doi: 10.1016/j.molcel.2020.02.005.
– Erdel F§, Kratz K§, Willcox S, Griffith JD, Greene EC*, de Lange T*. (2017). Telomere recognition and assembly mechanism of mammalian shelterin. Cell Rep 18: 41-53. doi: 10.1016/j.celrep.2016.12.005
