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During development, cells undergo numerous tightly regulated differentiation steps that are each characterized by distinct changes in gene expression to ultimately generate all the different cell types in the human body. The correct temporal and spatial gene expression patterns in these cell fate transitions are controlled by enhancers: short DNA sequences that regulate the expression of their target gene from a distance. Changes in the enhancer landscape have been mapped in numerous cell states, but how enhancers function to activate their target gene remains enigmatic. Furthermore, within a population of cells, each single cell initiates differentiation at a distinct time point. What leads to the initiation of differentiation and how do single cells transition from one cell state into the next, closely related one? Our lab wants to understand how these transcriptional changes driven by enhancers are orchestrated on the single cell level.
We study how enhancers are activated and regulate their target gene in a highly controlled developmental system: The exit from naïve pluripotency. In this differentiation, mouse embryonic stem cells transition into a transient cell state resembling the late post-implantation epiblast. Though combination of next generation sequencing based approaches both on population and on single cells, imaging to follow transcriptional changes using reporters, and CRIPSRP-Cas9 based genome wide screening methods we will dissect this cell fate transition in detail. Through focusing on one cell fate transition we will gain deep mechanistic insights into cellular decision making that will inform regenerative medicine approaches in the future.
Christa Buecker studied Biology at the University Stuttgart. She joined Niels Geijsen's lab at MGH and Harvard Stem Cell Institute in Boston, USA to study human pluripotency. For her postdoctoral work, she moved to Stanford to study transcriptional changes and enhancers in early embryonic development in Joanna Wysocka's lab. In 2015, she started her own group at Max Perutz Labs.
Epigenomic mapping has led to the identification of numerous putative enhancer elements within one cell state and often multiple enhancers can be found in the vicinity of one putative target gene. But how are these enhancer elements working together? We have dissected the enhancer elements that control the expression of Fgf5 during the exit from naive pluripotency. Surprisingly, individual elements had low intrinsic enhancer activity, however, multiple elements work together in a super-additive manner to activate the target gene at the endogenous locus. See our publication in Molecular Cell.
Stem cells express a set of genes that are normally upregulated in the event of infection. However, in stem cells, these interferon stimulated genes are not triggered through an external event, their regulation was so far unclear. During the exit from naive pluripotency, the same transcription factors that are driving the differentiation, are also responsible for the upregulating Irf1, a master transcription factor that protects cells from viral infection. See our publication in EMBO Reports.
Genome wide changes in the enhancer landscape during the exit from naïve pluripotency are driving by reorganization of the pluripotency master regulator Oct4 to newly activated enhancers through collaboration with Otx2. This work highlights the combinatorial nature of transcriptional regulation and builds the foundation to understand this cell fate transition in depths. See our publication in Cell Stem Cell.
Transient upregulation of IRF1 during exit from naive pluripotency confers viral protection.
Romeike, Merrit; Spach, Stephanie; Huber, Marie; Feng, Songjie; Vainorius, Gintautas; Elling, Ulrich; Versteeg, Gjis A; Buecker, Christa
Temporal dissection of an enhancer cluster reveals distinct temporal and functional contributions of individual elements.
Thomas, Henry F; Kotova, Elena; Jayaram, Swathi; Pilz, Axel; Romeike, Merrit; Lackner, Andreas; Penz, Thomas; Bock, Christoph; Leeb, Martin; Halbritter, Florian; Wysocka, Joanna; Buecker, Christa
Reorganization of enhancer patterns in transition from naive to primed pluripotency.
Buecker, Christa; Srinivasan, Rajini; Wu, Zhixiang; Calo, Eliezer; Acampora, Dario; Faial, Tiago; Simeone, Antonio; Tan, Minjia; Swigut, Tomasz; Wysocka, Joanna
Enhancers as information integration hubs in development: lessons from genomics.
Buecker, Christa; Wysocka, Joanna
A murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cells.
Buecker, Christa; Chen, Hsu-Hsin; Polo, Jose Maria; Daheron, Laurence; Bu, Lei; Barakat, Tahsin Stefan; Okwieka, Patricia; Porter, Andrew; Gribnau, Joost; Hochedlinger, Konrad; Geijsen, Niels
The Buecker is funded through a standalone grant reviewed and funded by the Austrian Research Fund FWF to explore to interaction and redundancies among transcription factors in the establishment of formative pluripotency.
The Group Buecker is a member of the special Doctoral Program "Signaling Mechanisms in Cellular Homeostasis" reviewed and funded by the Austrian Research Fund FWF.
The Group Buecker is a member of the special doc.funds Program "Stem Cells, Tissues, Organoids – Dissecting Regulators of Potency and Pattern Formation" reviewed and funded by the Austrian Research Fund FWF.
Now: Postdoc with Ludovic Vallier (Berlin Institute of Health at Charite Berlin)
Monday Seminar (Internal)
Speaker: WU Shuangyang (Dolan), SCARAMUZZA Federico (Tessmar), KROGULL Daniel (Burga)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
The recently discovered ties between teeth and infants in human evolution
Speaker: Leslea HluskoInstitute: CENIEHHost: Nicole Grunstra
Characterisation of Vpr1, a novel protein involved in DSB repair
Speaker: Mustafa AlaaboInstitute: Dept. Chromosome Biology, Univ. ViennaHost: Franz Klein
Probing multi-scale dynamics in complex fluids and biological systems with differential dynamic microscopy
Speaker: Roberto CerbinoInstitute: University of ViennaHost: Arthur Sedivy
Marine symbioses fueled by wood
Speaker: Dan DistelInstitute: Ocean Genome Legacy CenterHost: Jillian Petersen
New insights in gene regulation and chromatin folding by enhancers and cohesin
Speaker: Wouter de LaatInstitute: Hubrecht InstituteHost: Christa Bücker
Genetic approaches in human cells to expose 'hidden' biology
Speaker: Thijn BrummelkampInstitute: NKI / Oncode InstituteHost: Johannes Zuber
Molecular mechanism analysis involved in mitochondrial sheath formation and spermiation processes using gene-manipulated mice
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Exploiting a unique post-translational modification to enhance subunit selection and activity of a tumor suppressor complex
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From non-coding RNAs to non-canonical Mutations in Cancer
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Chemical tools to study nucleic acids by biophysical methods
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Microbial trait-based scaling from single populations to communities with consequences for ecosystem processes
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How chromosome architecture shapes brain architecture
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Comprehensive and quantitative characterization of aneuploidy phenotypes
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Cellular crosstalk in Neurodevelopmental Disorders
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Top down and bottom up exploration of human gut microbial communities
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Title to be announced
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The Mirage of Biosocial Complexity: Critique and Collaboration Around the Tools of Epigenetics
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Title to be announced
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Title to be announced
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Title to be announced
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Title to be announced
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Speaker: SHUNMUGAM Dhanlakshmi (Baccarini), CECI GINISTRELLI Lavinia (Mendjan), VORLÄNDER Matthias (Plaschka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
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Title to be announced
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Title to be announced
Speaker: Lydia FinleyInstitute: Memorial Sloan Kettering Cancer CenterHost: Johannes Zuber
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Speaker: STRAVS Ana (Knoblich), SANCHEZ DE MEDINA HERNANDEZ Victor (Dagdas), HORENKAMP Simone (Tanaka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: PROTELL I DE MONTSERRAT Julia (Brennecke/Plaschka), NAGUMO WONG Sakurako (Knoblich), CORIC Aida (Tessmar)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
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Title to be announced
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Monday Seminar (Internal)
Speaker: GRABARCZYK Daniel (Clausen), TAVERINI Katherina (Urban), MANCHENO JUNCOSA Estela (Mendjan)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Edward LemkeInstitute: IMB MainzHost: David Haselbach
Monday Seminar (Internal)
Speaker: ATTRILL Sarah (Dolan), UIJTTEWAAL Esther (Elling), SCIBISZ Grzegorz (Karagöz)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: DOLESCHALL Balint (Knoblich), FENG Sonjie (Bücker), BOURGUET Pierre (Berger)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Rotem SorekInstitute: Weizmann Institute of Science, RehovotHost: Julius Brennecke
Monday Seminar (Internal)
Speaker: KRUMWIEDE Luisa (Gaidt), KAPRAL Thomas (Zagrovic)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: KOBAKHIDZE George (Dong), ANGELOPOULOU Eleni (Ellis), PACHANO Tomas (Stark)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Stephan GrillInstitute: MPI of Molecular Cell Biology and GeneticsHost: Clemens Plaschka
Monday Seminar (Internal)
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Title to be announced
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Monday Seminar (Internal)
Speaker: LEITNER Moritz (Martinez), VOGEL Alexander (Yudushkin), KETTEL Paulina (Karagöz)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
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Monday Seminar (Internal)
Speaker: TSAREV Aleksandr (Ameres), FIESELER Charlie (Zimmer), ABESAMIS Kim Ivan (Dong)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
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Monday Seminar (Internal)
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Title to be announced
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Monday Seminar (Internal)
Speaker: KOLLER Manuela (Campbell), GUPTA Ankit (Goloborodko), SCHMÖLLERL Johannes (Zuber)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
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Monday Seminar (Internal)
Speaker: SALEWSKIJ Kirill (Penninger), KIRCHGATTERER Paul (Gaidt), REN Kaike (Otsuka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: MIHAILOVIC Milica (Karagöz), BELL Lillie (Clausen), TELONI Federico (Gerlich)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: STANKUNAS Edvinas (Köhler), LEV Itamar (Zimmer)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: OBERHUEMER Michael (Leeb), GONAZLEZ ALVARADO Maria (Grade), SCHOLZ Julia (Otsuka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: AMANN Sascha (Haselbach), KASHKO Nataliia (Matos), BAUER Bernd (Martens)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: LEE Joonsun (Elling), LEYVA GONZALEZ Marco (Tanaka), MILIVOJEV Nadja (Raible)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: GAO Peng (Dagdas), GOGOVA Rebeca (Clausen), PAVLOVA Anzhela (Matos)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: AYALA MUNOZ Farja (Plaschka), VETRANO Pamela (Ramundo), YU Changwei (Brennecke)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: KONSTANTINOU Andri (Obenauf), NAVA GARCIA Marintia (Dagdas), WOLFF Uyen Le Phuong (Jantsch V.)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: HARTMANN Felix (Matos), PASSERA Alessandro (Balzarotti), SANCHEZ BURGOS Laura (Obenauf)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: SILVA Raquel (Foisner), HODAKOVA Zuzana (Haselbach), MYLARSHCHIKOV Dmitry (Gerlich)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Johannes WalterInstitute: Harvard Medical SchoolHost: Jan-Michael Peters
Monday Seminar (Internal)
Speaker: PIECH Lucas (Leonard), DE LA CONCEPCION Juan Carlos (Dagdas), POPOVA Mariia (Peters)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
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Monday Seminar (Internal)
Speaker: KNIEST Judith (Haselbach), KELLNER Max (Penninger), BABADEI Olga (Decker)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: BOHAUMILITZKY Lena (Pinheiro), RAIDERS Stephan (Tanaka), PRLESI Ines (Gerlich)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
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Speaker: VELETI Lalitha (Pauli), ENGL Magdalena (Slade), NAAS Julia (Van Haeseler)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: FARAWAY Rupert (Plaschka), GRUNDMANN Lorenz (Haselbach), KLEINWAECHTER Ava (Slade)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
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Monday Seminar (Internal)
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Monday Seminar (Internal)
Speaker: RUSSETT Colleen (Berger), NAJM Ramsey (Knoblich), HOLLAUS David (Gaidt)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: SHARMA Sanskriti (Ellis), JANKOWSKA Julia (Ameres), PAPAREDDY Ranjith (Dagdas)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
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Speaker: MAURER Eric (Peters), BHARDWAJ Vishakha (Schlögelhofer), DIEZMA Laura (Nordborg/Mari-Ordonez)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
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Speaker: GUZMAN PEREZ Sebastian (Martinez), LITTLEBOY Jamie (Knoblich), RIABOV Daria (Plaschka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: ZEILER Christina (Kovarik), DOCAVO GARCIA Antonio (Jachowicz), Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
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Speaker: HUETTER Christiane (Menche), KRACHT Laura (Knoblich), SANDRU Ana Maria (Baccarini)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: BENEDUM Johannes (Slade), KALIS Robert (Zuber), PATEL Rajvi (Matos)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
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Speaker: PROTSENKO Liudmila (Brennecke), SHETTY Kavya (Hein), BASSAT Elad (Tanaka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs