Jun 3, 2022
Krebsforscherin Susan Gasser hält Hans Tuppy-Lecture
Feb 16, 2021
Extensive remodeling of chromatin after DNA damage
Feb 9, 2021
Interview Susan M. Gasser – Director Emeritus & Group Leader, FMI
Jan 14, 2021
Protecting the genome from transposon activation
Dec 7, 2020
Interview with Susan Gasser, FMI Director Emeritus
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|Video portrait (Inserm Prize 2011)|
|Susan Gasser CV|
Susan M. Gasser
Genome organization during differentiation and stress
Susan Gasser retired from the FMI at the end of 2020 and became the director of the Foundation of the Swiss Institute for Experimental Cancer (ISREC) in January 2021. The Gasser lab at the FMI closed at the end of June 2021.
The Gasser laboratory studies how chromatin, a complex of proteins and nucleic acids, impinges on mechanisms of DNA repair and replication, and on the epigenetic inheritance of cell fate decisions. We use high throughput time-lapse imaging to address questions of chromatin folding in living organisms. With respect to stem cell determination and epigenetic inheritance, we exploit the nematode C. elegans to study the effects of 3D chromatin organization during organismal development. We examine how the environment alters that program and we ask if these changes are epigenetically inherited from one stage of life to another. With respect to the mechanisms of repair, the budding yeast, S. cerevisiae provides a flexible genetic system that allows us to model DNA folding based on the spatial dynamics of chromosomal loci.
Specific areas of focus include:
1. Nuclear subcompartments: Transient long-range interactions within active, or potentially active, chromatin (TADs) and the more stable "condensates" of heterochromatin (LADs) drive chromatin organization in the nucleus. We use genetics to identify factors that spatially segregate large chromatin domains.
2. Chromatin dynamics in repair: Chromatin organization both protects from DNA damage and facilitates repair. We focus on dynamic changes in chromatin during repair and on the role of chromatin compaction in repeat stability.
3. Stress-induced epigenetic function: We are examining whether there is a "memory" function mediated by histone post-translational modifications that controls a stress response, enhancing organismal survival. These studies have a direct impact on the treatment of medical conditions.
Colin E Delaney, Stephen P Methot, Veronique Kalck, Jan Seebacher, Daniel Hess, Susan M Gasser, Jan Padeken (2022) SETDB1-like MET-2 promotes transcriptional silencing and development independently of its H3K9me-associated catalytic activityNat Struct Mol Biol. 10.1038/s41594-022-00776-w
Challa, K., Seebacher, J. and Gasser, S.M. (2021) Sucrose gradient chromatin enrichment for quantitative proteomic analysis in budding yeastSTAR protocols, doi: 10.1016/j.xpro.2021.100825, in press.
Saitoh, N. and Gasser, S.M. (2021) Nadeshiko revisited: The situation of women in Japanese research and the measures taken to increase their representationEMBO Reports. 22, e52528. dx.doi.org/10.15252/embr.202152528.
Fuchs J., Cheblal A., Gasser S.M. (2021) Underappreciated Roles of DNA Polymerase δ in Replication Stress SurvivalTrends Genet. 37, 476 - 487. doi: 10.1016/j.tig.2020.12.003.
Hurst, V., Shimada, K. and Gasser, S.M. (2019) Nuclear actin and actin binding proteins in DNA repairTrends Cell Biol. 29, 462 - 476. doi: 10.1016/j.tcb.2019.02.010.
Hurst, V., Challa, K., Jonas, F., Forey, R., Sack, R., Seebacher, J., Schmid, C.E., Barkai, N., Shimada*, K., Gasser*, S.M. and Poli*, J. (2021) A regulatory phosphorylation site on Mec1 controls chromatin occupancy of RNA polymerases during replication stressEMBO J. doi: 10.15252/embj.2021108439. in press
Shimada. K., van Loon, B., Gerhold, C.B., Bregenhorn, S., Hurst, V., Roth, G., Tarashev, C., Heinis, C., Jiricny, J. and Gasser, S.M. (2021) Uncoordinated long-patch base excision repair at juxtaposed DNA lesions generates a lethal accumulation of double-strand breaksNature Comms in revision, and BioRXiv doi: 10.1101/ 2020.11.15.383513
Shimada, K., Tsai-Pflugfelder, M., Davoodi Vijeh Motlagh, N., Delgoshaie, N., Fuchs, J., Gut, H. and Gasser, S.M. (2021) The Stabilized Pol31-Pol3 interface counteracts Pol32 ablation with differential effects on repair.Life Sci Alliance. 4(9): e202101138. doi: 10.26508/lsa.202101138.
Challa K, Schmid CD, Kitagawa S, Cheblal A, Iesmantavicius V, Seeber A, Amitai A, Seebacher J, Hauer MH, Shimada K, Gasser SM (2021) Damage-induced chromatome dynamics link Ubiquitin ligase and proteasome recruitment to histone loss and efficient DNA repair.Molecular Cell, 81, 811 - 829. doi: 10.1016/j.molcel.2020.12.021.
Padeken J, Methot S, Zeller P, Delaney CE, Kalck V, Gasser SM (2021) Argonaute NRDE-3 and MBT domain protein LIN-61 redundantly recruit an H3K9me3 HMT to prevent embryonic lethality and transposon expression.Genes & Dev. 35, 82 - 101. doi: 10.1101/gad.344234.120.
Forey R, Barthe A, Tittel-Elmer M, Wery M, Barrault MB, Ducrot C, Seeber A, Krietenstein N, Szachnowski U, Skrzypczak M, Ginalski K, Rowicka M, Cobb JA, Rando OJ, Soutourina J, Werner M, Dubrana K, Gasser SM, Morillon A, Pasero P, Lengronne A, Poli J (2021) A Role for the Mre11-Rad50-Xrs2 Complex in Gene Expression and Chromosome Organization.Molecular Cell, 81, 183 - 197. doi:10.1016/j.molcel.2020.11.010
Cheblal A, Challa K, Seeber A, Shimada K, Yoshida H, Ferreira HC, Amitai A, Gasser SM (2021) DNA Damage-Induced Nucleosome Depletion Enhances Homology Search Independently of Local Break Movement.Molecular Cell, 64, 951 - 966. doi: 10.1016/j.molcel.2016.10.032
Harr JC, Schmid CD, Munoz-Jiménez C, Romero-Bueno R, Kalck V, Gonzalez-Sandoval A, Hauer MH, Padeken J, Askjaer P, Mattout A, Gasser SM (2020) Loss of an H3K9me anchor rescues laminopathy-linked changes in nuclear organization and muscle function in an Emery-Dreifuss muscular dystrophy model.Genes & Dev. 34, 560 - 579. doi:10.1101/gad.332213.119
Mattout A, Gaidatzis D, Padeken J, Schmid CD, Aeschimann F, Kalck V, Gasser SM (2020) LSM2-8 and XRN-2 contribute to the silencing of H3K27me3-marked genes through targeted RNA decay.Nature Cell Biology, 22, 579 - 590. doi: 10.1038/s41556-020-0504-1.
Deshpande, I., Keusch, J., Challa, K., Iesmantavicius, V., Gasser, S.M. and Gut, H. (2019) A Sir4 H-BRCT domain interacts with phospho-proteins to sequester and repress yeast heterochromatinEMBO J. 38(20), e101744. doi: 10.15252/embj.2019101744.
Delaney, CE, Methot, SP, Guidi, M, Katic, I, Gasser, SM, Padeken, J. (2019) Heterochromatic foci and transcriptional repression by an unstructured MET-2/SETDB1 co-factor LIN-65J. Cell Biol. 218, 820 - 838. doi: 10.1083/jcb.201811038.
Padeken J, Zeller P, Towbin B, Katic I, Kalck V, Methot SP, Gasser SM. (2019) Synergistic lethality between BRCA1 and H3K9me2 loss reflects satellite derepression.Genes & Dev. 33, 436 - 451. doi: 10.1101/gad.322495.118.
Cabianca, D.S., Munoz Jimenez, C., Kalck, V., Gaidatzis, D., Padeken, J., Seeber, A., Askjaer, P. and Gasser, S.M. (2019) Active chromatin marks drive spatial sequestration of heterochromatin in C. elegans nucleiNature, 569, 734 - 739. doi: 10.1038/s41586-019-1243-y.