FISchmidtLab

Cell Biology meets Immunology and Virology, spiced up with nanobodies

[FISchmidtLab @FISchmidtLab]

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.
https://t.co/DmCnqN8Chl

[FISchmidtLab @FISchmidtLab]

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. https://t.co/MdgETQduNF

[Jonathan Schmid-Burgk @schmidburgk]

How could we identify key genes involved in any biological process and cell type? Please read on about Nuclear In-Situ Sequencing (NIS-Seq)
https://t.co/AnBlEYS0yR

[FISchmidtLab @FISchmidtLab]

@IpbsToulouse @MariaMMota2 @LennonLab This was truly a lot of fun - excellent talks at @IpbsToulouse (and was also spoiled with good food). Thanks to all the students and staff members for organizing this!

[Marion Koopmans, publications: https://pure.eur.nl @MarionKoopmans]

and so it begins.....science needs to start getting serious about how how to deal with this type of attacks, sowing distrust.

[FISchmidtLab @FISchmidtLab]

Check out Lisa‘s take on her recent paper on the mechanism (and potential therapeutic targeting) of #GSDMD pore formation using #nanobodies.

[ImmunoSensation @ImmunoSens]

🎬 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: https://t.co/AU2xJV7IFm

[Felipe Opazo @FelipeOpaz_o]

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: https://t.co/mCtlJsKCRR

[ISMMSscopes @ISMMSscopes]

😯😯

[Dagmar Wachten & lab @DagmarWachten]

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

[Charlie Evavold, find me @synth-immune.bsky.social @Synth_Immune]

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 @FISchmidtLab]

In parellel work, @anja_kopp @Geyer_lab solved the structure of two of our #nanobodies bound to #GSDMD. https://t.co/Mz4JKPCRlc.
The Feng Shao lab also used #AAV to express one of our #GSDMD #nanobodies to prevent loss of the #BBB during sepsis.
https://t.co/bpBxpMhBwA

[FISchmidtLab @FISchmidtLab]

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 .

[FISchmidtLab @FISchmidtLab]

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 ...

[FISchmidtLab @FISchmidtLab]

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!

[FISchmidtLab @FISchmidtLab]

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.

[FISchmidtLab @FISchmidtLab]

As cells no longer die by #pyroptosis, stabilized, endogenous #GSDMD in the plasma membrane can even stained with antibodies for cleaved GSDMD.

[FISchmidtLab @FISchmidtLab]

Surprisingly, expression of antagonistic #GSDMD #nanobodies stabilized monomeric GSDMD NTD-mNeonGreen in the plasma membrane.

[FISchmidtLab @FISchmidtLab]

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 ...

[FISchmidtLab @FISchmidtLab]

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 ....

[FISchmidtLab @FISchmidtLab]

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.
https://t.co/DmCnqN8Chl

[Doherty Institute @TheDohertyInst]

✨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! https://t.co/xZ6CdclvuA @UniMelbMDHS @TheRMH @UniMelb