Thread by @TheBinderLab

New paper out! Our own David Zander has successfully published his thesis work in @cddpress’ Cell Death & Disease!

Just to highlight this: David is an MD but he worked his tail off pipetting this study! A big Thank You to @TRR179_2 for the stipend!

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nature.com/articles/s4141…

So what is it about?
• Damage to our cells’ genome DNA can lead to #cancer if it goes unnoticed (cell not committing suicide).
• Vice versa, many chemotherapies (and radiotherapy!) are based on killing cells by inducing #DNADamage.

In his study, David used…
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…live cell microscopy (@EssenBioScience) to monitor cell proliferation and death upon treatment with doxorubicin (chemotherapeutic inducing DNA breaks) or gamma-irradiation (γIR). As expected, both treatments kill cells ⬇️

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Strikingly, absence of one of the major antiviral defense systems, the RIG-I/IRF3 axis (and #NFkB), significantly reduced cell death. Surprise: this was independent of #interferon (IFNR TKO = KO of type I, II and III IFN receptors) and having more #RIGI (OE) *increased* death!
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David could identify a further dependency using our collection of KO cells: the antiviral transcription factor IRF1. Again a surprise: IRF1 expression was independent or RIG-I and also IFNs, but depended on the DNA damage sensors ATM/ATR.

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How ATM/ATR signals to IRF1 (via NFkB it seems), and how the RIG-I/IRF3 axis independently regulates cell death in this context unfortunately remains elusive so far. But hey, that’s what keeps our job so exciting! :)

A huge congrats and THANKS to David in any case! Great work!

David is not on Twitter (afaik), but let me tag and thank the other co-authors as well, who contributed alot: @Sandy_Niesik, @VladimirMagalh and Sandra Wüst (who’s also not on Twitter). And @DrechslerMaike and @Joschka87038668 who deserve a solid acknowledgement!