Greg Findlay

Group Leader of the Genome Function Laboratory @TheCrick
From 2025, find me over on the other side:

[Greg Findlay @TheGenomeLab]

Great to see this out now in @CellGenomics . A few points about what we learned in revisions over on BlueSky:
https://t.co/4g2Hww4qab

[Greg Findlay @TheGenomeLab]

Our latest from @TheCrick, now on @biorxivpreprint:

https://t.co/5KYA031Wja

Michael Herger (@HergerMichael) and Christina Kajba jointly led development of a new prime editing platform for testing large numbers of human genetic variants.

[Greg Findlay @TheGenomeLab]

@AkramulSourav Dear Akramul,
Yes - Crick PhD positions are open to international students! Out of fairness, I don't discuss project opportunities with individual applicants until shortlisting, but please apply using the link above if interested.
Best,
Greg

[Greg Findlay @TheGenomeLab]

Crick PhD recruitment for fall 2025 is officially open! Please apply to our lab through the Crick application portal if interested. 👇

https://t.co/fVnzOTFmey

[David Balchin @balchin_david]

Join us for a PhD! Applications close November 5th. https://t.co/HkJ0QBZvLM

[David Balchin @balchin_david]

New from our lab @TheCrick , led by @BetkaRoe. A fun side project that tried to understand what happens when a chaperonin encounters a translating ribosome.
https://t.co/2t0cpKIMKl

[Colleen Drapek @ColleenDrapek]

Come join us in making agriculture sustainable at @PhytoformLabs! 🌱We are looking for an R&D scientist with a background in Synthetic biology to join our tools & traits team for precision genome editing 🧬. If you think this could be you, please apply!

https://t.co/xCCUz8IbQ8

[Nicky Whiffin @nickywhiffin]

So excited that our paper “De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome” is out today in @Nature https://t.co/FeDLGm14MB
🧵 1/16

[The Francis Crick Institute @TheCrick]

We are delighted to announce that Professor Edith Heard has been appointed as our new director and chief executive!

Edith, who is currently director-general at @EMBL, will succeed Paul Nurse in leading the Crick from the summer of 2025.

🔗 https://t.co/CcJR4TFxbF

[Chloé Terwagne @ChloeTerwagne]

Want to fully investigate this large dataset beyond classical 2D formats? Go interactively explore the data 👇
https://t.co/3eW7gUL8Nw

[Greg Findlay @TheGenomeLab]

@JohnDoench @megan_buckley01 @NatureGenet Yes, the van ride! So critical... ;)

Thanks, John!

[Greg Findlay @TheGenomeLab]

Our work led by @megan_buckley01 on Saturation Genome Editing of VHL is now out in @NatureGenet:

https://t.co/HytcJynmkT

Many new experiments and analyses to quickly highlight… (1/n)

[Greg Findlay @TheGenomeLab]

@SaraGutierrezEn @megan_buckley01 @NatureGenet Thanks, Sara!

[Greg Findlay @TheGenomeLab]

Finally, we’re delighted to see this published back-to-back with a massive SGE analysis of BAP1 led by Andrew Waters, @David_J_Adams and co. @sangerinstitute:

https://t.co/G98Rju7DpM

So many more variants now readily interpretable, and still more on the way! (9/9)

[Greg Findlay @TheGenomeLab]

Massive thanks to all authors, but particularly @ChloeTerwagne, Athina Ganner, @LauraCubitt3, @ReidBrewer3, Dong-Kyu Kim & @Eivakine for key inputs to revisions. And, of course, many thanks to reviewers, @nature_genet, and funders @TheCrick @CRUKresearch (7/n)

[Greg Findlay @TheGenomeLab]

Of course, we hope you read the paper and use the data. Do feel free to reach out with questions on anything from protocol tips to variant classifications.
(8/n)

[Greg Findlay @TheGenomeLab]

Lots more new analyses and validations in the paper, too. For instance, comparing function scores to SpiceAI and FoldX computational predictions – both of which do reasonably well. (6/n)

[Greg Findlay @TheGenomeLab]

In new experiments, we also characterise novel mechanisms made apparent by SGE. Specifically, we show that a long C-terminus extension leads to LoF via VHL protein destablization and that stop-codon readthrough can impact the degree of functional impairment. See Fig. 6! (5/n)

[Greg Findlay @TheGenomeLab]

Importantly, we now split loss-of-function variants by SGE score into LOF1 (lowest) and LOF2 (depleted, weaker effect).

In collaboration w Athina Ganner and Freiburg colleagues, we show how patients with VHL disease can be stratified by ccRCC risk using these categories. (4/n)

[Greg Findlay @TheGenomeLab]

The VHL data can also be searched, visualised, and explored using this awesome SGE visualisation platform made by @ChloeTerwagne:

https://t.co/YEtNHhzcl4

Chloé’s code is all on GitHub if you’re interested in viewing and sharing your own data like this. (3/n)

[Greg Findlay @TheGenomeLab]

Most importantly, all SGE scores and variant classifications are available for download in Supplementary Table 1 and from MAVEdb (https://t.co/v5CF8oJ9dw).

Given the data’s high precision, we expect this will lead to a steep reduction in VUS reported clinically. (2/n)