@FISchmidtLab

Cell Biology meets Immunology and Virology, spiced up with nanobodies

 Bonn, Germany
tinyurl.com/FISchmidtLaboratory
Joined May 2018
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Ever wondered why there is so little #microscopy of #GSDMD pores? Check out how Lisa Schiffelers used #Nanobodies to stabilize monomeric GSDMD in the plasma membrane, to dissect the steps of pore formation, and to develop some new ideas for therapy. nature.com/articles/s41467-0…
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Late #WeekendRead: We describe a novel reporter to visualize endogenous #inflammasome assembly. Suitable for cell lines, primary cells, and tissues as well as quantification by #microscopy and #flowcytometry. Happy to share. biorxiv.org/content/10.1101/…
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How could we identify key genes involved in any biological process and cell type? Please read on about Nuclear In-Situ Sequencing (NIS-Seq) nature.com/articles/s41587-0…

NIS-Seq enables cell-type-agnostic optical perturbation screening

Nature Biotechnology - An optical pooled screening method can correlate phenotypes and perturbations in any nucleated cell type.

nature.com
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and so it begins.....science needs to start getting serious about how how to deal with this type of attacks, sowing distrust.
SARS‑CoV‑2 (COVID-19)
@COVID19_disease9 Nov 2024
RFK Jr. Dismantles Journalist's Appeal to Authority Journalist: "You're a lawyer and activist, not a doctor or scientist." RFK Jr.: "Relying on experts is akin to religious faith and totalitarianism. In a democracy, we question everyone."
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Check out Lisa‘s take on her recent paper on the mechanism (and potential therapeutic targeting) of #GSDMD pore formation using #nanobodies.
ImmunoSensation@ImmunoSens30 Oct 2024
🎬 Episode 11 of #SpotOnScience is out! In this episode, Lisa Schiffelers from the group of @FISchmidtLab shares insights into her work on unraveling gasdermin D (GSDMD) pore formation using nanobodies. 👩‍🔬 Check out the episode: youtube.com/watch?v=HvgNf5o8…
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It is out! #NanoPlex is the universal strategy for multiplexing any immunofluorescence using erasable #nanobodies from @_NanoTag_. We showcase easy multiplexed STED, STORM, and 21-plex Confocal #Microscopy. Published in @NatureComms here: rdcu.be/dWvzO
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FISchmidtLab retweeted
ISMMSscopes@ISMMSscopes11 Oct 2024
😯😯
Felipe Opazo@FelipeOpaz_o10 Oct 2024
It is out! #NanoPlex is the universal strategy for multiplexing any immunofluorescence using erasable #nanobodies from @_NanoTag_. We showcase easy multiplexed STED, STORM, and 21-plex Confocal #Microscopy. Published in @NatureComms here: rdcu.be/dWvzO
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Teaching the next generation of scientists all about what we do in the lab #TürenaufmitderMaus – big thank you to my whole lab and, in particular, Fabian @IIIBonn @for5547 #sfb1454 @ImmunoSens
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Epic effort from Flo & first author Lisa Schiffelers of @FISchmidtLab . Antagonistic camelid #nanobodies are small enough to traverse early #GSDMD pores to inhibit further #pore #formation. Monomers target the membrane, suggesting #monomer to #oligomer transition on #membrane.
FISchmidtLab@FISchmidtLab26 Sep 2024
Ever wondered why there is so little #microscopy of #GSDMD pores? Check out how Lisa Schiffelers used #Nanobodies to stabilize monomeric GSDMD in the plasma membrane, to dissect the steps of pore formation, and to develop some new ideas for therapy. nature.com/articles/s41467-0…
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In parellel work, @anja_kopp @Geyer_lab solved the structure of two of our #nanobodies bound to #GSDMD. nature.com/articles/s41467-0…. The Feng Shao lab also used #AAV to express one of our #GSDMD #nanobodies to prevent loss of the #BBB during sepsis. nature.com/articles/s41586-0…

Pyroptosis inhibiting nanobodies block Gasdermin D pore formation

Nature Communications - Pyroptosis has been implicated in many diseases with aberrant inflammation. Here, Kopp et al. characterize single-chain nanobodies targeting the human gasdermin D protein as...

nature.com
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Special thanks to all the lab members who helped during the revision, including @YM_Tesfamariam, Lea, Stefan, Sabine and Steffen. This work was done at @IIIBonn @UniBonn @UniklinikBonn with funding by @ImmunoSens @sfb_1403 @237Crc .
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We think the antagonistic GSDMD #nanobodies enter cells when the first #GSDMD pores form. They prevent any further pore formation and thus -in combination with cellular repair mechanism- prevent cell death by pyroptosis. We are looking forward to test this concept in vivo ...
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As #nanobodies enter pyroptotic cells (left), Lisa also tested if recombinant #nanobodies prevent pyroptosis when added to the medium during #inflammasome activation (right). They do!
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We learn: 1. The plasma membrane is the first #GSDMD target membrane, 2. Cleavage of #GSDMD is sufficient to allow membrane insertion (no prepore required), and 3. #GSDMD pores are rapidly removed as soon as pores form.
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As cells no longer die by #pyroptosis, stabilized, endogenous #GSDMD in the plasma membrane can even stained with antibodies for cleaved GSDMD.
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Surprisingly, expression of antagonistic #GSDMD #nanobodies stabilized monomeric GSDMD NTD-mNeonGreen in the plasma membrane.
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We had previously tried to use a cool tool from @inflammgenetics to visualize #GSDMD pores in living cells (mNeonGreen remains with the #GSDMD NT), but mostly found GSDMD in intracellular structures ...
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We raised #alpaca #nanobodies against #GSDMD and found that two cytosolically expressed nanobodies completely shut down pore formation, #pyroptosis, and cytokine release after #inflammasome activation ....
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✨Today officially marks 10 years of @TheDohertyInst. From pioneering research on the immune system to our response to COVID-19, we’re incredibly proud of our staff and students and their achievements in infection and immunity. And a huge thank you to our supporters. Here’s to another 10 years and beyond! go.unimelb.edu.au/2cc8 @UniMelbMDHS @TheRMH @UniMelb
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