Julian Grünewald

Congrats on this great work, @jmathony.bsky.social @dominikniopek.bsky.social & team!

Rational engineering of allosteric protein switches by in silico prediction of domain insertion sites Nature Methods - ProDomino is a machine leaning-based method, trained on a semisynthetic domain insertion dataset, to guide the engineering of protein domain recombination.

Publication alert: Our paper on domain insertion predictions in proteins is now out in @natmethods.nature.com in its final form: rdcu.be/ey7w3
Also check out the nice perspective by @noahholzleitner.bsky.social and @grunewald.bsky.social : www.nature.com/articles/s41...

Rational engineering of allosteric protein switches by in silico prediction of domain insertion sites - Nature Methods ProDomino is a machine leaning-based method, trained on a semisynthetic domain insertion dataset, to guide the engineering of protein domain recombination.

Our work on rationally engineering allosteric protein switches is now out in Nature Methods: www.nature.com/articles/s41... Thanks a lot to @grunewald.bsky.social and @noahholzleitner.bsky.social for the comprehensive news and views: www.nature.com/articles/s41...

Dual SORT LNPs for multi-organ base editing - Nature Biotechnology Optimized SORT LNPs enable precise and long-lasting base editing in dual organs in a disease mouse model.

Dual SORT LNPs for multi-organ base editing go.nature.com/3HC9EHt

A promising genetic treatment tailor-made for a baby born with a rare disorder For the first time, doctors have created a customized treatment using the revolutionary gene-editing technique known as CRISPR to treat a baby with a rare, life-threatening genetic disorder.

For the first time, doctors have created a customized treatment using the revolutionary gene-editing technique known as CRISPR to treat a baby with a rare, life-threatening genetic disorder.

Today "a milestone in the evolution of personalized therapies for rare & ultra-rare inborn errors of metabolism"
—the 1st human to undergo custom genome editing
—from decades of NIH funded research
www.nejm.org/doi/full/10....
@nejm.org
www.nejm.org/doi/full/10....
www.nytimes.com/2025/05/15/h...

Evolution-guided protein design of IscB for persistent epigenome editing in vivo - Nature Biotechnology A combination of engineering approaches is used to improve the function of IscB for a variety of editing activities in vivo.

Evolution-guided protein design of IscB for persistent epigenome editing in vivo - @zhangf.bsky.social @broadinstitute.org @hhmi.org go.nature.com/44XVBph

By combining high-throughput protein engineering with machine learning, bespoke SpCas9 enzymes are identified that outperform evolution-based and engineered nucleases and base editors in human cells. www.nature.com/articles/s41... #NBTHighlight

AlphaFold is amazing but gives you static structures 🧊

In a fantastic teamwork, @mcagiada.bsky.social and @emilthomasen.bsky.social developed AF2χ to generate conformational ensembles representing side-chain dynamics using AF2 💃

Code: github.com/KULL-Centre/...
Colab: github.com/matteo-cagia...

AAV vectors trigger DNA damage response-dependent pro-inflammatory signalling in human iPSC-derived CNS models and mouse brain Nature Communications - Costa-Verdera et. al describe a mechanism by which AAV vector genomes activate P53-mediated signalling in CNS cells involving downstream STING activation and...

We are super excited to share our work on #InnateImmune sensing of #AAV 🦠🧬 in the 🧠, just out in @natcomms.nature.com ! 🤩

Huge congratulations to all the team and collaborators 💪🏻

And our funders 💰
@erc.europa.eu #FondazioneTelethon and #FNIH 🙏🏻

www.nature.com/articles/s41...

Our latest work now online in Cell:

Rewriting regulatory DNA to dissect and reprogram gene expression

Our new method (Variant-EFFECTS) uses high-throughput prime editing + flow sorting + sequencing to precisely measure effects of noncoding variants on gene expression

Thread 👇

RFDiffusion2: a diffusion model that scaffolds enzyme active sites at the atomic level enables the generation of functional de novo enzymes

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

Engineered nucleocytosolic vehicles for loading of programmable editors Engineered nucleocytosolic vehicles for loading of programmable editors (ENVLPE) with enhanced CRISPR ribonucleoprotein (RNP) loading and stabilization enable the efficient delivery of gene-editing ef...

www.cell.com/cell/fulltex...
ENVLPE, our system for VLP-based delivery of gene editors, is now published in @cellcellpress.bsky.social. We showed efficient delivery of base- and prime-editors in primary T cells & in vivo retinal models. All core constructs are available from @addgene.bsky.social.

CRISPRi-ART enables functional genomics of diverse bacteriophages using RNA-binding dCas13d - Nature Microbiology Leveraging RNA-targeting dCas13d enables selective interference with phage protein translation and facilitates measurement of phage gene fitness at a transcriptome-wide scale.

Dive into our lab’s first peer-reviewed publication—co-led with our friends @benadler.bsky.social and Muntathar Al-Shimary from the @doudna lab! If you’ve already read the preprint, don’t miss the new updates: doi.org/10.1038/s415... @naturemicrobiol.bsky.social

Making intrabodies from antibodies just got easier! Learn how we made 𝟭𝟵 intrabodies to bind and light up peptides and histone modifications in live cells. And thanks to Academia, all sequences are freely available. (video credit: Yuko Sato @YukoSatoT2) (1/15)
www.biorxiv.org/content/10.1...

Twitter:
LNP/mRNA therapeutics and AAV-based approaches require cell-level precision to achieve success without significant toxicity to other cells. To enable this, we developed SCP-Nano: an AI and tissue-clearing-based technology for precision nanotechnology. www.nature.com/articles/s41...

Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning - Nature Biotechnology An integrated experimental and deep learning pipeline reveals cell-level targeting of nanocarriers in whole bodies.

New paper from our lab (@erturklab.bsky.social)

We show how tissue clearing, light sheet microscopy, and AI-based image analysis can be combined to determine the biodistribution and drug delivery efficiency of nanocarriers throughout entire mouse bodies with single-cell resolution.

Engineered extrachromosomal oncogene amplifications promote tumorigenesis - Nature Large extrachromosomal DNAs are engineered using a CRISPR- and Cre–loxP-based approach and shown to drive cancer in mouse models, with potential applications in determining the role of oncogene a...

🧪1/ 🚨New paper on ecDNAs from our lab!
We reveal a strategy to engineer extrachromosomal DNA (ecDNA) amplifications in cells & mice. Let's dive in! Let’s dive in! 🧵👇
www.nature.com/articles/s41...

Method of the Year 2024: spatial proteomics - Nature Methods Approaches for profiling the spatial proteome in tissues are the basis of atlas-scale projects that are delivering on their promise for understanding biological complexity in health and disease.

I could not be more thrilled to announce the Nature Methods @naturemethods.bsky.social Method of the Year is Spatial Proteomics! Please see our editorial as a roadmap to the fantastic content in this special issue! www.nature.com/articles/s41...

Imagine seeing a disease's impact on every cell in the body. Now, you can! We introduce MouseMapper, an AI tool to reveal system-wide disease perturbations. It reveals obesity-induced changes in facial nerves & body-wide inflammation 👉🧵https://biorxiv.org/content/10.1101/2024.08.18.608300v1.full.pdf

Our new preprint is out - please share!

We asked: How can we make CRISPR knockouts in vivo more efficient? And set up an assay that enables detection of CRISPR cutting with 100s-1000s of sgRNAs over entire chromosome arms in living animals.

Grab a ☕ and let’s dive in. 🧵🧪 1/n
#CRISPR #geneediting

By definition, enhancers can activate from a distance. But with increased distance between enhancer and promoter, the activation drops. To study this systematically, we build a synthetic locus: www.cell.com/molecular-ce... 1/12

2X #DilatedCardiomyopathy GWAS MATG #NatGenet 2024 reveal novel genes/cellular players

PROX1 - #LymphaticEndothelialCell
ERG - #EndothelialCell
DGKG - #SmoothMuscleCell
MAPT/Tau validated in both studies

>9k case
www.nature.com/articles/s41...

>14k case
www.nature.com/articles/s41...

Online @cellpress.bsky.social, we reveal a protein shell that helps diatoms fix 20% of global #CO2 🧪🌊🌾🧶🧬🌍

Shimakawa et al:
www.cell.com/cell/fulltex...

Nam et al:
www.cell.com/cell/fulltex...

@biozentrum.bsky.social press release:
www.biozentrum.unibas.ch/news/detail/...

Read on for more...
1/🧵

Figure from the linked paper showing that recruitment of Cas9 to nascent RNA via MS2 or boxB increases targeting of nearby cut sites.

Interesting concept. Recruiting Cas9 to nascent transcripts allows coupling of editing efficiency to expression of the target gene.

www.nature.com/articles/s41...

#CRISPR

This is really interesting. It's probably a great way to deal with resistance mutations in the future.

Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19 SARS-CoV-2 infection can lead to long-lasting neurological sequelae, but underlying mechanisms are unclear. Rong et al. report that SARS-CoV-2 spike protein persists in the skull-meninges-brain axis, ...

New paper from our lab @erturklab.bsky.social

www.cell.com/cell-host-mi...

Thanks a lot @olehdmy.bsky.social! I hope you’re doing well.