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Griffiths Lab

@griffithslab.bsky.social
85 followers 10 following 12 posts

Discovering the remarkable intracellular dynamics of killer T cells

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Griffiths Lab @griffithslab.bsky.social · 04/08/2025
This phenomenon is called "transcriptional adaptation", as coined by @stainierlab.bsky.social Consistent with their NMD-mediated mechanism, we found targeting the promoter of Cdc42 avoids TA in CTLs. It also seems to be specific for CDC42 among Rho GTPases in CTLs.
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Griffiths Lab @griffithslab.bsky.social · 04/08/2025
Multi-omics revealed that the knockout cells were compensating for the loss of CDC42 by transcriptionally upregulating genes that could enhance T cell function, including by upregulating the activity of related Rho GTPases!
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Griffiths Lab @griffithslab.bsky.social · 04/08/2025
CRISPR/Cas9-mediated gene deletion normally requires several days of recovery before assaying cellular function. When we performed killing assays daily after delivery of RNPs, we found that the knockout cells initially pheno-copied inhibited cells, but then regained functionality over time
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Griffiths Lab @griffithslab.bsky.social · 04/08/2025
Inhibiting CDC42 with a chemical inhibitor (CASIN) gave the opposite result: worsened CTL function. Meanwhile, the knockout cells showed *enhanced* function regardless of inhibitor treatment ...
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Griffiths Lab @griffithslab.bsky.social · 04/08/2025
Confusingly, we found the knockout cells performed *better* than control cells across killing, degranulation, migration, and signalling.
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Griffiths Lab @griffithslab.bsky.social · 04/08/2025
Sometimes, knocking out a gene isn't a good way to figure out the function of that gene ... In our new @jcellsci.bsky.social paper, we report potent transcriptional adaptation by cytotoxic T lymphocytes (CTLs) in response to CRISPR/Cas9-mediated deletion of the important polarity protein CDC42 🧵⬇️
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Griffiths Lab @griffithslab.bsky.social · 17/01/2025
As promised at my seminar at NCBS, here is the video showing what happens to the centrosome in a “confused T cell” that is contacting two targets with equal signals.
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Griffiths Lab @griffithslab.bsky.social · 08/01/2025
Welcome to the dynamic world of T cells!
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