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Silvia Domcke
@sdomcke
Exploring the world of transcription factors and gene regulation. Scientist and mountain enthusiast. @sdomcke.bsky.social
Joined June 2020
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    New synthetic biology / gene regulation lab opening in Zurich! We’re studying how to control cell state transitions – for example, making diseased cells healthy or creating new cellular functions – using systematic perturbations, single-cell genomics and machine learning. 🧵1/4
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    First foray into single cell genomics, first postdoc paper, first tweet! Excited to share our human cell atlas of fetal chromatin accessibility, a very fun collaboration with @JShendure @ahill_tweets Riza Daza @cusanovich and others. science.sciencemag.org/content/370/65… (1/5)
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    Excited to see my final PhD work published @NatureGenet (rdcu.be/c02lQ)! How does DNA methylation repress genes? Through direct inhibition of transcription factor (TF) binding at the motif OR indirect inhibition via sequence-independent recruitment of MBD proteins? 1/6
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    Ever been frustrated by the Wild West of cell type annotations in single cell datasets? @JShendure and I propose constructing consensus data-driven 'reference cell trees', inclusive of both lineage histories and molecular states. authors.elsevier.com/c/1glnfL7PXmbl-
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    Indeed best ever postdoc advisor. My n=1, but convinced would be the same if n=1000 (and Germans don’t exaggerate). So well deserved for being an equally amazing and inspiring scientist, mentor and human. Congrats to being elected to NAS @JShendure.
    Congratulations to my best ever postdoc advisor Jay @JShendure on being elected to the NAS! Anyone else feels this was overdue?!
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    Replying to @sdomcke
    Want to be part of this adventure? We’re looking for new lab members with experimental and/or computational interests, see our website for more information on our research and how to join: domcke.github.io/domcke-lab.html 2/4
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    Check out @FloChardon and @TroyMcDiarmid's preprint on using CRISPRa to screen for cell type-specific regulatory elements. Somehow they manage to be great scientists and labmates while also being semi-professional cyclists/skateboarders on the side!
    Absolutely thrilled to share mine and @TroyMcDiarmid’s work describing the development of a multiplexed, scalable CRISPRa cell type-specific screening framework that is able to identify…(1/n) biorxiv.org/content/10.110…
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    Replying to @sdomcke
    Excited to return to Europe, after a mind-opening, fun and crazy six years in the Pacific Northwest, including an enriching excursion into the San Francisco biotech start-up world with @GordianBio. There are many people and places I’ll miss. 3/4
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    Replying to @sdomcke
    Grateful to my mentors @JShendure @SchubelerLab @coletrapnell for their support in this journey, and all my wonderful lab mates, collaborators and friends in the @JShendure lab. 4/4
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    Replying to @sdomcke
    Deleting all four MBDs results in only a limited transcriptional response in stem, differentiated, mouse and human cells. Multiple lines of evidence indicate that direct inhibition of TF binding at motifs is instead the prevailing mode of repression by DNA methylation. 3/6
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    Replying to @sdomcke
    We identify and validate new TFs that are blocked from binding by DNA methylation of their motifs. In its absence, some of them induce rampant activation of endogenous retroviruses (ERVs) by binding to CG-containing motifs in the ERVs’ long terminal repeats. 5/6
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    We talk about diversity, but self-limit it along many axes by discouraging diverse career paths. Delaying your lab start due to challenges like family relocation or experience in industry/ a new field shouldn't make you ineligible for a starting grant. One size does not fit all.
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    Replying to @sdomcke
    Transcriptional control by methylation-sensitive TFs could benefit the expansion of ERVs by being compatible with expression in hypomethylated states in the germline while ensuring repression in somatic cells. 6/6
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    Replying to @Duboule
    Foucault indeed quotes a passage from a Borges essay, who in turn attributes it to a translation of a Chinese source ('Celestial Emporium of Benevolent Knowledge') by Franz Kuhn, but that is likely fictional. Borges essay is in fact very pertinent to the subject and worth reading