First pre-print from the lab, a collaborative effort led by Jess Bourn @bournsupremacy.bsky.social, a fantastic PhD in my group. We resolve a key problem in development + evolution: how do we quantify heterochrony and link temporal variation to phenotype? www.biorxiv.org/content/10.6...

Quantitative mapping of heterochrony to species-specific phenotypes

The genetic program of animal development is conserved, but its rate of execution varies across species. Heterochrony, shifts in the relative timing of developmental events, generates phenotypic varia...

biorxiv.org

How much of the human genome is essential? Two pieces out today from our lab: 1) a method to map essential genomic intervals at gigabase scale, and 2) an argument that it's time to consider synthesizing a minimal human genome. biorxiv.org/content/10.6... nature.com/articles/d41...

Why a synthetic human genome is still worth building

A decade on from the launch of an ambitious project, it’s time to revisit the reasons for constructing a human genome from scratch.

nature.com

1/n What fraction of the human genome is essential for cells? Excited to share our preprint that explores this question by combining an unusual CRISPR system, phage promoters, and thousands of deletion launchpads. @sudpinglay.bsky.social @jshendure.bsky.social www.biorxiv.org/content/10.6...

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).

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)👇

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...

biorxiv.org

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...

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...

biorxiv.org

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

Leopold Parts@leopoldparts.bsky.social · 2y ago

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/...

@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

Genome recombination on demand

Large genome rearrangements in mammalian cells can be generated at scale

science.org

🧬@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

Leopold Parts@leopoldparts.bsky.social · 2y ago

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/...

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

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/...

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) ...

science.org

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...

science.org

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/...

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...

science.org

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!

Neville Sanjana@nevillesanjana.bsky.social · 2y ago

🎇🎄Some holiday reading: Overdue TWEETORIAL on the latest preprint from our lab 🎇🎄 In this work, superstar postdoc @xinhexue.bsky.social combined 2 kinds of pooled CRISPR screens to pinpoint noncoding regulatory elements and the transcription factors that activate these elements.

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 .

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

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...

nature.com