Exciting research from the labs of MCB’s David Savage @savagecatsonly.bsky.social and Christina Listgarten, featuring MCB postdoc Maria Lukarska @marialukarska.bsky.social! 🧬🔬

QB3-Berkeley@qb3-berkeley.bsky.social · 4w ago

Protein engineers at UC Berkeley created ProteinGuide—a method using experimental data to steer generative AI models toward better, highly stable & active proteins without expensive model retraining. Read more about this @ucberkeleyofficial.bsky.social research: bit.ly/4AlhcFC

We are PUBLISHED!!! Our mechanistic work on how CRISPR-Cas ancestors unwind DNA and how this can be used to engineer hypercompact plant editors can now be found on Mol Cell- if you are interested in what defines a good genome editor, this read is for you 😎 🔗 www.sciencedirect.com/science/arti...

Our ProteinGuide paper is finally out! Thanks to all the co-authors @junhaobearxiong.bsky.social, @ishangaur.bsky.social, @hnisonoff.bsky.social, @loltrogge.bsky.social, @jlistgarten.bsky.social, @savagecatsonly.bsky.social! @innovativegenomics.bsky.social www.nature.com/articles/s41...

Property guidance for protein sequence generative models with ProteinGuide - Nature Biotechnology

On-the-fly conditioning of pretrained protein generative models guides protein generation toward specific properties.

nature.com

Property guidance for protein sequence generative models with ProteinGuide - @jlistgarten.bsky.social @savagecatsonly.bsky.social www.nature.com/articles/s41...

Property guidance for protein sequence generative models with ProteinGuide - Nature Biotechnology

On-the-fly conditioning of pretrained protein generative models guides protein generation toward specific properties.

nature.com

Check out our new preprint on base editors and the thread below!

@marialukarska.bsky.social · 3mo ago

I’m happy to share our pre-print exploring the activity and specificity trade-offs in adenine base editors. Thanks to my amazing co-authors Luke Oltrogge, @hnisonoff.bsky.social, and all the other contributors @jlistgarten.bsky.social @savagecatsonly.bsky.social @innovativegenomics.bsky.social 🧵1/7

I’m happy to share our pre-print exploring the activity and specificity trade-offs in adenine base editors. Thanks to my amazing co-authors Luke Oltrogge, @hnisonoff.bsky.social, and all the other contributors @jlistgarten.bsky.social @savagecatsonly.bsky.social @innovativegenomics.bsky.social 🧵1/7

Activity and specificity trade-offs in adenine base editors

Adenine base editors (ABEs) are CRISPR effectors that introduce A-T to G-C transitions in the genome using a nucleotide deaminase fused to a Cas protein. ABEs have been evolved to have very high editi...

biorxiv.org

New preprint from Dave Savage (Savage Lab) and Yun S. Song: Deep models of protein evolution in time generate realistic evolutionary trajectories and functional proteins. Read here: https://ow.ly/iJk950YCF8q #AI #AIresearch

Can CRISPR edits enable precise tuning of plant gene expression? We think: yes. In our newest manuscript, we measured the effects of >30,000 CRISPR-like promoter mutations in sorghum protoplasts.

Mapping cis-regulatory mutations at scale in sorghum enables modulation of gene expression - @savagecatsonly.bsky.social go.nature.com/3O7mDEN

Engineered TnpB genome editors for plants and human cells identified by ribonucleoprotein mutational scanning - @savagecatsonly.bsky.social go.nature.com/4loaOGn

Engineered TnpB genome editors for plants and human cells identified by ribonucleoprotein mutational scanning - Nature Biotechnology

TnpB endonucleases are engineered for improved genome editing.

go.nature.com

How do the ancestors of CRISPR-Cas unwind DNA and how can this lead to better genome editing? With our collaboration between @doudna-lab.bsky.social x @jacobsenucla.bsky.social x Zev Bryant's lab x @savagecatsonly.bsky.social we've uncovered the secrets behind TnpB's dynamics!

New from Ugrappa Nagalakshmi and Jorge Rodriguez 🌱✂️– Gene editing in plants just got a lot easier! Using engineered TnpB, they demonstrate high-efficiency, heritable, transgene-free editing in plants. (1/7)

Congrats to our savage lab undergrads on their research and presentations in our inaugural undergrad research symposium 🎉🥳

‼️ New pre-print from co-leads @owentuck.bsky.social and Jason Hu! Check out this fascinating example of how coevolution enables defense system innovation.

Owen Tuck@owentuck.bsky.social · last yr.

Excited to finally share this work! We noticed a pair of genes - a nuclease and a protease - shuffles between antiviral systems. We show how proteolysis activates the nuclease, triggering defense in known and unknown immune contexts. tinyurl.com/2uwwy4ty

We love generating data! But what should we do with it? We collaborated w/ the Listgarten lab on ProteinGuide - a new method for using experimental data to guide protein generative models. Congrats to @junhaobearxiong.bsky.social, @hnisonoff.bsky.social, @marialukarska.bsky.social, Ishan, & Luke! ⬇️

Junhao (Bear) Xiong@junhaobearxiong.bsky.social · last yr.

Guide your favorite protein generative model with experimental data? Meet ProteinGuide - a method to condition pre-trained models on properties without retraining. We validated it both in silico by guiding ProteinMPNN and ESM3 on 3 tasks and in vitro by engineering base editors.

Excited to share our new preprint on mutational scanning of the TnpB RNP! We identify several highly activating, single-position mutations in TnpB’s protein and reRNA. These datasets enabled us to engineer enhanced TnpB protein variants (>50x plant editing levels compared to WT).

Savage Lab@savagecatsonly.bsky.social · 2y ago

What's better than 1 deep mutational scanning (DMS) library? 2! In a new pre-print @brittneywthornton.bsky.social and @rfw.bsky.social et al. map the mutational landscape of ISDra2 TnpB protein and reRNA and leverage these datasets to engineer highly active variants (1/9)

It is finally out! Muntathar Al-Shimary, @doudna-lab.bsky.social , @cresslab.bsky.social and I present a gene knockdown tool that works in diverse bacteriophages: CRISPRi through antisense RNA Targeting (CRISPRi-ART)! Check it out @naturemicrobiol.bsky.social www.nature.com/articles/s41...

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.

nature.com

What's better than 1 deep mutational scanning (DMS) library? 2! In a new pre-print @brittneywthornton.bsky.social and @rfw.bsky.social et al. map the mutational landscape of ISDra2 TnpB protein and reRNA and leverage these datasets to engineer highly active variants (1/9)

New research from IGI Investigator Dave Savage @savagecatsonly.bsky.social and first author Noam Prywes @prywes.bsky.social (pictured) details the landscape of possible Rubisco variants, suggesting ways to make the world's most abundant enzyme better at its job. 🌱🧪🧬 Read more: ow.ly/t2JO50ULh10

What limits rubisco function? Is it the chemical mechanism? Evolution? In this paper, @prywes.bsky.social et. al explore this question by assaying >99% of single amino acid mutants in Form II rubisco (1/7) doi.org/10.1038/s415...

New research from IGI Investigator Dave Savage and first author Noam Prywes details the landscape of possible Rubisco variants, suggesting ways to make the world's most abundant enzyme better at its job. 🌱 Read more: ow.ly/t2JO50ULh10