Umberto Aiello
@umbertoaiello.bsky.social
@EMBO postdoc fellow in the lab of @LarsMSteinmetz at @Stanford. Previously at @SapienzaRoma, @univ_paris_cite & @CNRS. I feed on pasta and RNA.
5/ Please read more in the full preprint, and if you would like to scan your favorite protein, let’s talk!
Finally, huge thanks to @embo.org and @stanfordmedicine.bsky.social for their support! And to Lars Steinmetz and Kevin Roy for making this possible!
Finally, huge thanks to @embo.org and @stanfordmedicine.bsky.social for their support! And to Lars Steinmetz and Kevin Roy for making this possible!
September 10, 2025 at 3:40 PM
5/ Please read more in the full preprint, and if you would like to scan your favorite protein, let’s talk!
Finally, huge thanks to @embo.org and @stanfordmedicine.bsky.social for their support! And to Lars Steinmetz and Kevin Roy for making this possible!
Finally, huge thanks to @embo.org and @stanfordmedicine.bsky.social for their support! And to Lars Steinmetz and Kevin Roy for making this possible!
4/…but also surprising lethality in the CTD-interacting domain (CID), a region previously thought to be dispensable for viability!
CID mutants are lethal, yet don’t show transcription termination defects.
This hints at distinct mechanisms of dysfunction, perhaps aberrant complex formation
CID mutants are lethal, yet don’t show transcription termination defects.
This hints at distinct mechanisms of dysfunction, perhaps aberrant complex formation
September 10, 2025 at 3:40 PM
4/…but also surprising lethality in the CTD-interacting domain (CID), a region previously thought to be dispensable for viability!
CID mutants are lethal, yet don’t show transcription termination defects.
This hints at distinct mechanisms of dysfunction, perhaps aberrant complex formation
CID mutants are lethal, yet don’t show transcription termination defects.
This hints at distinct mechanisms of dysfunction, perhaps aberrant complex formation
3/ As proof-of-concept, we scanned NRD1, an essential transcription termination factor.
We reached near-saturation mutagenesis with ~95% of residues edited.
We tracked mutational fitness and found clusters of lethal substitutions where we expected them (the RNA recognition motif)…
We reached near-saturation mutagenesis with ~95% of residues edited.
We tracked mutational fitness and found clusters of lethal substitutions where we expected them (the RNA recognition motif)…
September 10, 2025 at 3:40 PM
3/ As proof-of-concept, we scanned NRD1, an essential transcription termination factor.
We reached near-saturation mutagenesis with ~95% of residues edited.
We tracked mutational fitness and found clusters of lethal substitutions where we expected them (the RNA recognition motif)…
We reached near-saturation mutagenesis with ~95% of residues edited.
We tracked mutational fitness and found clusters of lethal substitutions where we expected them (the RNA recognition motif)…
2/ Most proteins work through just a handful of crucial residues, but finding and interpreting them in essential genes is tough, since mutating them = lethality ⚰️
Our solution: combine multiplexed CRISPR editing with a repressible complementation system
Our solution: combine multiplexed CRISPR editing with a repressible complementation system
September 10, 2025 at 3:40 PM
2/ Most proteins work through just a handful of crucial residues, but finding and interpreting them in essential genes is tough, since mutating them = lethality ⚰️
Our solution: combine multiplexed CRISPR editing with a repressible complementation system
Our solution: combine multiplexed CRISPR editing with a repressible complementation system