Latest from Shendure & Qiu labs (@cxqiu.bsky.social)
)! We combined a new 4M cell mouse whole embryo scATAC-seq atlas (E10-P0), millions of 'evolutionarily coherent' orthologs from 241 mammalian genomes (Zoonomia), and the CREsted CNN framework (@steinaerts.bsky.social).

Generating long deletions across the genome with pooled paired prime editing screens Engineered deletions are a powerful probe for studying genome architecture, function, and regulation. Yet, the lack of effective methods to create them in large numbers and at multi-kilobase scale has...

New 🧬✂️ pre-print! We show that paired prime editing can efficiently generate large deletions — even >1 Mb — with high precision and at scale. We use this to perform the first pooled prime deletion screen across the human genome.

🔗 biorxiv.org/content/10.1...

A short thread (by Juliane Weller)👇

Enhancer-promoter compatibility is mediated by the promoter-proximal region Gene promoters induce transcription in response to distal enhancers. How enhancers specifically activate their target promoter while bypassing other promoters remains unclear. Here, we find that the p...

What is a promoter? And how does it work?

We very happy to share our latest work trying to understand enhancer-promoter compatibility.
I am very excited about the results of @blanka-majchrzycka.bsky.social, which changed the way I think about promoters

www.biorxiv.org/content/10.1...

Super excited about first Shendure/Baker Lab collaboration & preprint on a multiplex sequencing-based strategy for screening de novo proteome editors in mammalian cells. Kudos to the brilliant Chase Suiter (not here) & @greenahn.bsky.social on the work! Preprint here:
www.biorxiv.org/content/10.1...

We're hiring to expand on the work to understand the human genome by engineering it!
lnkd.in/da-gitNc

Genome recombination on demand Large genome rearrangements in mammalian cells can be generated at scale

@science.org Genome recombination on demand | Science www.science.org/doi/10.1126/... a Perspective by @seczmarta.bsky.social Lars Steinmetz @stanford.edu on two studies bit.ly/4hzFRMg + bit.ly/4jyT4Hf that generate large genome rearrangements in mammalian cells @ unprecedented scale #synbio #genome

🧬@science.org Randomizing the human genome by engineering recombination between repeat elements bit.ly/4jyT4Hf @jonaskoeppel.bsky.social @f-raphael.bsky.social @geochurch.bsky.social @proftomellis.bsky.social @leopoldparts.bsky.social +al. @sangerinstitute.bsky.social @harvardmed.bsky.social #synbio

If tinkering with genomes - designing, writing, shuffling and augmenting them excites you, come join us! We are hiring at all levels.

www.pinglay-lab.com

Multiplex generation and single-cell analysis of structural variants in mammalian genomes Studying the functional consequences of structural variants (SVs) in mammalian genomes is challenging because (i) SVs arise much less commonly than single-nucleotide variants or small indels and (ii) ...

Now out in @science.org w/ @jshendure.bsky.social we present 'Genome-shuffle-seq': a method to shuffle mammalian genomes and characterize the impact of structural variants (SVs) with single-cell resolution in one experiment.

www.science.org/doi/10.1126/...

Nothing much to add here from my side! It was in fact a very similar situation with @f-raphael.bsky.social and us. We connected for a different reason and figured out we both tried to insert loxP sites into LINE1 and then decided to join forces

Randomizing the human genome by engineering recombination between repeat elements We lack tools to edit DNA sequences at scales necessary to study 99% of the human genome that is noncoding. To address this gap, we applied CRISPR prime editing to insert recombination handles into re...

Rearranging mammalian genomes with recombinases to study structural variants at scale provides insights into genome organization and dispensability #NBTHighlight
www.science.org/doi/10.1126/... and www.science.org/doi/10.1126/...

Randomizing the human genome by engineering recombination between repeat elements We lack tools to edit DNA sequences at scales necessary to study 99% of the human genome that is noncoding. To address this gap, we applied CRISPR prime editing to insert recombination handles into re...

We're delighted to share our work on scrambling the human genome using prime editing, repetitive elements, and recombinases in @science.org , led by @jonaskoeppel.bsky.social , @f-raphael.bsky.social , with @proftomellis.bsky.social and George Church.
www.science.org/doi/10.1126/...

Enhancer scrambling strategy

We are happy to share our enhancer scramble story, a strategy to create hundreds of stochastic deletions, inversions, and duplications within mammalian gene regulatory regions and associate these new architectures with gene expression levels 🧵
www.biorxiv.org/content/10.1...

Excited to share my latest preprint on establishing a generalizable toolkit for decoding the gene regulatory landscape using two types of CRISPR screens. Big thanks to my amazing mentor @nevillesanjana.bsky.social for the in-depth thread below. Looking forward to feedback and comments!

Does my mutation have the same impact as yours? Population genetics 🤠 🥸 🤓 🤡 meets single cell CRISPRi ⚡ ! www.biorxiv.org/content/10.1... Led by Claudia Feng, Oliver Stegle, Britta Velten, @sangerinstitute.bsky.social .

Engineering structural variants to interrogate genome function - Nature Genetics Structural variations (SVs) impact gene expression, genome stability and disease susceptibility. This Review discusses recent advances in genome-engineering tools that enable precise SV generation and...

Structural variants are ripe for interrogation using genome engineering. Jonas Koeppel Juliane Weller Thomas Vanderstichele (Wellcome Sanger Institute) and I review technology progress, insights gained to date, and challenges and promise for the road ahead. www.nature.com/articles/s41588-024-01981-7