Stefan Holderbach
@sholderbach.bsky.social
Playing with programming languages, proteins, and photography. Nerding out about Nushell and niche applications of synthetic biology.
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...
1/28 How do you optimize a dynamic protein property that emerges from multiple states? Our finally published paper in @NatureComms takes on one of the hardest problems in protein engineering with phage assisted evolution: evolving allosteric switches🧵
Are you interested in working with a fresh team on cutting edge protein design? We're hiring a Technical Assistant for our protein design team at DKFZ Heidelberg: jobs.dkfz.de/en/jobs/1683... Please share!
Technical Assistant
jobs.dkfz.de
Not sure how to reconcile A) bindcraft consistently outperforming RFDiffusion, but B) AF3-gen diffusion-based design outperforming AF3-gen hallucination-based design. My best guess is that there's something about AF2 but not AF3-gen methods that makes them amenable to backprop?
Rust 1.90.0 is out! blog.rust-lang.org/2025/09/18/R... Major features: * lld as the default linker on x86_64-unknown-linux-gnu * cargo workspace publishing support built into cargo * more const context APIs, and stabilization of new useful APIs
Announcing Rust 1.90.0 | Rust Blog
Empowering everyone to build reliable and efficient software.
blog.rust-lang.org
Exciting to see our protein binder design pipeline BindCraft published in its final form in @Nature ! This has been an amazing collaborative effort with Lennart, Christian, @sokrypton.org, Bruno and many other amazing lab members and collaborators. www.nature.com/articles/s41...
overheard, with regards to nushell "That is pretty cool that you can just do that kind of stuff with the shell scripting. " 🩵
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.
rdcu.be
Excited to share work with Zhidian Zhang, @milot.bsky.social, @martinsteinegger.bsky.social, and @sokrypton.org biorxiv.org/content/10.1... TLDR: We introduce MSA Pairformer, a 111M parameter protein language model that challenges the scaling paradigm in self-supervised protein language modeling🧵
Scaling down protein language modeling with MSA Pairformer
Recent efforts in protein language modeling have focused on scaling single-sequence models and their training data, requiring vast compute resources that limit accessibility. Although models that use ...
biorxiv.org
MMseqs2 v18 is out - SIMD FW/BW alignment (preprint soon!) - Sub. Mat. λ calculator by Eric Dawson - Faster ARM SW by Alexander Nesterovskiy - MSA-Pairformer’s proximity-based pairing for multimer prediction (www.biorxiv.org/content/10.1...; avail. in ColabFold API) 💾 github.com/soedinglab/M... & 🐍
Our paper benchmarking foundation models for perturbation effect prediction is finally published 🎉🥳🎉 www.nature.com/articles/s41... We show that none of the available* models outperform simple linear baselines. Since the original preprint, we added more methods, metrics, and prettier figures! 🧵
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...
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.
nature.com
I talk a lot about Rust for building high-perf (& even non-perf critical) software, & scientific software in particular. I often discuss what's interesting to me, but wanted to offer the chance to those interested for me to answer their questions about Rust in science. Fire away with questions!🧬🖥️
Absolutely spoiled by match and if/else being expressions in Rust and Nushell. Really feels pedestrian trying to achieve the same in Typescript or Python. (No the ternary operator is not "control flow as expressions" we have at home)
#AwesomeTools 1: uv docs.astral.sh/uv/ has transformed how I work with Python projects locally and for development and distribution. No more pip, venv, poetry, etc. seamless package management, virtual environments, development and deployment deliverer FAST & without hassle!
uv
uv is an extremely fast Python package and project manager, written in Rust.
docs.astral.sh
Rust 1.88.0 has been released! ✨🎊 🦀 This release brings you let chains, naked functions, automatic Cargo cache cleaning, Cell::update, proc_macro span locations, as_chunks methods on slices, and more! Check out the blog post and release notes for all the details: blog.rust-lang.org/2025/06/26/R...
Announcing Rust 1.88.0 | Rust Blog
Empowering everyone to build reliable and efficient software.
blog.rust-lang.org
Excited to share my main PhD work is finally out! 🥳 We built a phage-assisted evolution platform to evolve allosteric protein switches (POGO-PANCE) and introduce cumulative, targeted mutations/Indels (RAMPhaGE)! See how we evolved ultra-strong, light-switchable AraC variants 🌚🌞
bioRxiv Synthetic Biology@biorxiv-synthbio.bsky.social · last yr.Phage-Assisted Evolution of Allosteric Protein Switches https://www.biorxiv.org/content/10.1101/2025.06.12.659331v1
I started tgv to learn Rust and building it has been unbelievably fun! If you wanna pick up a super fast and fun programming language, tgv is open for contribution! There aren't many bioinformatics tools built entirely by the community. If tgv can become one, I'll be so psyched
Stephen Turner@stephenturner.us · last yr.Terminal Genome Viewer (tgv), written in Rust github.com/zeqianli/tgv
New paper alert! We introduce the modular allosteric thermo-control of protein activity. Employing the AsLOV2 domain and mutants thereof as thermoreceptors, we engineered diverse hybrid proteins, whose activity can be controlled by small temperature changes (37-40/41 °C). doi.org/10.1101/2025...
doi.org
Nushell 0.104 is out: www.nushell.sh/blog/2025-04... gh's @cosineblast continues to iterate on job support, with experimental support for message passing between jobs
AFESM: a metagenomic guide through the protein structure universe! We clustered 821M structures (AFDB&ESMatlas) into 5.12M groups; revealing biome-specific groups, only 1 new fold even after AlphaFold2 re-prediction & many novel domain combos. 🧵 🌐 afesm.foldseek.com 📄 www.biorxiv.org/content/10.1...
"If you're used to being able to sit down and bang out code, any time, anywhere, with all kinds of tools (libraries, compilers, virtual machines, what have you) at your fingertips, then yeah, working up a new assay protocol in a cell line is going to seem agonizingly slow" (from 2015)
Derek Lowe@dereklowe.bsky.social · last yr.We have an exciting new PhD opportunity! If you are fsacinated by proteins and their dynamics and want to engineer them to develop new molecular tools: apply now! We are a young and dynamic team combining state-of-the-art laboratory and bioinformatics approaches. Please share.
Labeling your axes and then explaining them slowly is perhaps the biggest bang for the buck you can get for making your slides more understandable.
Using Rust for Bioinformatics tackling the complexity of VCF with a common scripting language (lua) Color me intrigued! github.com/brentp/vcfex...
GitHub - brentp/vcfexpress: expressions on VCFs
expressions on VCFs. Contribute to brentp/vcfexpress development by creating an account on GitHub.
github.com
Rob Patro@robp.bsky.social · last yr.This is very cool work and I'm happy to see it published. Vcfexpress by @brent-p.bsky.social and @aaronquinlan.bsky.social allows building (essentially) arbitrary VCF filters expressed in lua code with parsing & eval powered by rust! academic.oup.com/bioinformati...
Excited to share a new preprint! Wireless devices use FM modulation to transmit multiplexed noise-resistant data. Led by @born2raisecell.bsky.social, we create a biochemical analogue of this paradigm using genetically encoded oscillators (GEOs) for single-cell FM streaming tinyurl.com/nbs8rw42 🧵
