Greg Findlay

Great to see this out now in @CellGenomics . A few points about what we learned in revisions over on BlueSky: bsky.app/profile/gregfi…

@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

@TheGenomeLab Dear Dr. Greg Findlay, Is this open for international students? This research project perfectly aligns with my research interest. Can I get your email to talk about the possible opportunities? Thank you.

Crick PhD recruitment for fall 2025 is officially open! Please apply to our lab through the Crick application portal if interested. 👇 crick.ac.uk/careers-study/…

RT @balchin_david: Join us for a PhD! Applications close November 5th. crick.ac.uk/careers-study/…

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. biorxiv.org/content/10.110…

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! linkedin.com/jobs/view/3972…

RT @nickywhiffin: So excited that our paper “De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome” is out toda…

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. 🔗 crick.ac.uk/news/2024-07-0…

RT @ChloeTerwagne: Want to fully investigate this large dataset beyond classical 2D formats? Go interactively explore the data 👇 https://t.…

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

Our work led by @megan_buckley01 on Saturation Genome Editing of VHL is now out in @NatureGenet: nature.com/articles/s4158… Many new experiments and analyses to quickly highlight… (1/n)

@SaraGutierrezEn @megan_buckley01 @NatureGenet Thanks, Sara!

@TheGenomeLab @megan_buckley01 @NatureGenet WOW, Greg! What a piece of incredibly useful data for variant classification. This will greatly benefit VHL cancer-related patients, providing better and personalized clinical management for their tumors👏🏽👏🏽

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: nature.com/articles/s4158… So many more variants now readily interpretable, and still more on the way! (9/9)

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)

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)

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)

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)

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)

The VHL data can also be searched, visualised, and explored using this awesome SGE visualisation platform made by @ChloeTerwagne: vhl-board.onrender.com Chloé’s code is all on GitHub if you’re interested in viewing and sharing your own data like this. (3/n)

Most importantly, all SGE scores and variant classifications are available for download in Supplementary Table 1 and from MAVEdb (mavedb.org/experiments/ur…). Given the data’s high precision, we expect this will lead to a steep reduction in VUS reported clinically. (2/n)