Noah Holzleitner
@noahholzleitner.bsky.social
PhD Student at Grünewald Lab (TUM)
🧬Protein Design for CRISPR proteins🧑🏽💻👨🏽🎨
🧬Protein Design for CRISPR proteins🧑🏽💻👨🏽🎨
Reposted by Noah Holzleitner
if you don't like the huge extended helices or alpha solenoid proteins you're getting from hallucination-based protein design methods (bindcraft, mosaic, etc), increasing the scale of the initial sequence noise (typically Gumbel) increases funkiness without hurting final metrics like ipTM
February 17, 2026 at 9:24 PM
if you don't like the huge extended helices or alpha solenoid proteins you're getting from hallucination-based protein design methods (bindcraft, mosaic, etc), increasing the scale of the initial sequence noise (typically Gumbel) increases funkiness without hurting final metrics like ipTM
Reposted by Noah Holzleitner
The fitness landscapes of binders targeting protein surfaces that are evolutionarily predisposed to engage in PPIs is much narrower and deeper than those that target surfaces with no known interacting proteins. This might be b/c random binding events is bad, and selected against
February 16, 2026 at 10:35 PM
The fitness landscapes of binders targeting protein surfaces that are evolutionarily predisposed to engage in PPIs is much narrower and deeper than those that target surfaces with no known interacting proteins. This might be b/c random binding events is bad, and selected against
Reposted by Noah Holzleitner
🎉🎉 Our paper on temperature-dependent protein control using AsLOV2 variants is now published at @natchembio.nature.com: www.nature.com/articles/s41... including some new insights from extend variant characterizations.
February 12, 2026 at 11:46 AM
🎉🎉 Our paper on temperature-dependent protein control using AsLOV2 variants is now published at @natchembio.nature.com: www.nature.com/articles/s41... including some new insights from extend variant characterizations.
Reposted by Noah Holzleitner
How could a simple self-replicating system emerge at the origins of life? RNA polymerase ribozymes can replicate RNA, but existing ones are so large that their self-replication seems impossible. Could they be smaller?
Excited to share our latest work in @science.org on a new small polymerase.
1/n
Excited to share our latest work in @science.org on a new small polymerase.
1/n
A small polymerase ribozyme that can synthesize itself and its complementary strand
The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural ...
www.science.org
February 13, 2026 at 11:42 AM
How could a simple self-replicating system emerge at the origins of life? RNA polymerase ribozymes can replicate RNA, but existing ones are so large that their self-replication seems impossible. Could they be smaller?
Excited to share our latest work in @science.org on a new small polymerase.
1/n
Excited to share our latest work in @science.org on a new small polymerase.
1/n
Reposted by Noah Holzleitner
I made a map of 3.4 million Bluesky users - see if you can find yourself!
bluesky-map.theo.io
I've seen some similar projects, but IMO this seems to better capture some of the fine-grained detail
bluesky-map.theo.io
I've seen some similar projects, but IMO this seems to better capture some of the fine-grained detail
Bluesky Map
Interactive map of 3.4 million Bluesky users, visualised by their follower pattern.
bluesky-map.theo.io
February 8, 2026 at 10:59 PM
I made a map of 3.4 million Bluesky users - see if you can find yourself!
bluesky-map.theo.io
I've seen some similar projects, but IMO this seems to better capture some of the fine-grained detail
bluesky-map.theo.io
I've seen some similar projects, but IMO this seems to better capture some of the fine-grained detail
Reposted by Noah Holzleitner
Introducing The Structural History of Eukarya (SHE): The first proteome-scale phylogeny constructed entirely from 3D structure.
We computed 300 trillion alignments across 1,542 species to map the tree of life. 🧵👇 (1/5)
We computed 300 trillion alignments across 1,542 species to map the tree of life. 🧵👇 (1/5)
February 7, 2026 at 8:50 AM
Introducing The Structural History of Eukarya (SHE): The first proteome-scale phylogeny constructed entirely from 3D structure.
We computed 300 trillion alignments across 1,542 species to map the tree of life. 🧵👇 (1/5)
We computed 300 trillion alignments across 1,542 species to map the tree of life. 🧵👇 (1/5)
Reposted by Noah Holzleitner
🧬🌉Online @science.org Programmable genome editing in human cells using RNA-guided bridge recombinases | Science www.science.org/doi/10.1126/...
Programmable genome editing in human cells using RNA-guided bridge recombinases
Site-specific insertion of gene-sized DNA fragments remains an unmet need in the genome editing field. IS110-family serine recombinases have recently been shown to mediate programmable DNA recombinati...
www.science.org
February 6, 2026 at 12:12 AM
🧬🌉Online @science.org Programmable genome editing in human cells using RNA-guided bridge recombinases | Science www.science.org/doi/10.1126/...
Reposted by Noah Holzleitner
🗓️ Save the Date!
The 5th European RosettaCon – Crossing Boundaries with Protein Design will take place in Lisbon, Portugal 🇵🇹
🗓️ October 28–30, 2026
Join the protein design community for an inspiring scientific meeting at the intersection of innovation and design.
The 5th European RosettaCon – Crossing Boundaries with Protein Design will take place in Lisbon, Portugal 🇵🇹
🗓️ October 28–30, 2026
Join the protein design community for an inspiring scientific meeting at the intersection of innovation and design.
February 3, 2026 at 6:05 AM
🗓️ Save the Date!
The 5th European RosettaCon – Crossing Boundaries with Protein Design will take place in Lisbon, Portugal 🇵🇹
🗓️ October 28–30, 2026
Join the protein design community for an inspiring scientific meeting at the intersection of innovation and design.
The 5th European RosettaCon – Crossing Boundaries with Protein Design will take place in Lisbon, Portugal 🇵🇹
🗓️ October 28–30, 2026
Join the protein design community for an inspiring scientific meeting at the intersection of innovation and design.
Reposted by Noah Holzleitner
Does the noncoding genome actually carry more genetic information than coding seqs? Motivated by this question we mutated every bp in the 10kb MYC locus. Results are even more exciting: Decoding the MYC locus reveals a druggable ultraconserved RNA element www.biorxiv.org/content/10.6...
www.biorxiv.org
January 31, 2026 at 1:13 AM
Does the noncoding genome actually carry more genetic information than coding seqs? Motivated by this question we mutated every bp in the 10kb MYC locus. Results are even more exciting: Decoding the MYC locus reveals a druggable ultraconserved RNA element www.biorxiv.org/content/10.6...
Reposted by Noah Holzleitner
FoldMason is out now in @science.org. It generates accurate multiple structure alignments for thousands of protein structures in seconds. Great work by Cameron L. M. Gilchrist and @milot.bsky.social.
📄 www.science.org/doi/10.1126/...
🌐 search.foldseek.com/foldmason
💾 github.com/steineggerla...
📄 www.science.org/doi/10.1126/...
🌐 search.foldseek.com/foldmason
💾 github.com/steineggerla...
Multiple protein structure alignment at scale with FoldMason
Protein structure is conserved beyond sequence, making multiple structural alignment (MSTA) essential for analyzing distantly related proteins. Computational prediction methods have vastly extended ou...
www.science.org
January 30, 2026 at 6:11 AM
FoldMason is out now in @science.org. It generates accurate multiple structure alignments for thousands of protein structures in seconds. Great work by Cameron L. M. Gilchrist and @milot.bsky.social.
📄 www.science.org/doi/10.1126/...
🌐 search.foldseek.com/foldmason
💾 github.com/steineggerla...
📄 www.science.org/doi/10.1126/...
🌐 search.foldseek.com/foldmason
💾 github.com/steineggerla...
Reposted by Noah Holzleitner
China’s innovation in translational medicine: rethinking early-stage clinical development - @caidyacro.bsky.social go.nature.com/4agbEkG
January 27, 2026 at 5:58 PM
China’s innovation in translational medicine: rethinking early-stage clinical development - @caidyacro.bsky.social go.nature.com/4agbEkG
Reposted by Noah Holzleitner
Neat paper! Boosting to the MP feed 🧬
Construction of complex and diverse DNA sequences using DNA three-way junctions
doi.org/10.1038/s415...
doi.org/10.1038/s415...
Construction of complex and diverse DNA sequences using DNA three-way junctions - Nature
Sidewinder enables high-fidelity DNA assembly by separating the information that guides assembly from the final assembled sequence.
doi.org
January 22, 2026 at 1:20 PM
Neat paper! Boosting to the MP feed 🧬
Reposted by Noah Holzleitner
EDEN: a family of genomic language models trained on up to 9.7 trillion nucleotides from @basecamp-research.bsky.social's BaseData can design large serine recombinases, bridge recombinases, and antimicrobial peptides.
www.biorxiv.org/content/10.6...
Happy to have played a small part in this!
www.biorxiv.org/content/10.6...
Happy to have played a small part in this!
January 13, 2026 at 3:16 PM
EDEN: a family of genomic language models trained on up to 9.7 trillion nucleotides from @basecamp-research.bsky.social's BaseData can design large serine recombinases, bridge recombinases, and antimicrobial peptides.
www.biorxiv.org/content/10.6...
Happy to have played a small part in this!
www.biorxiv.org/content/10.6...
Happy to have played a small part in this!
Reposted by Noah Holzleitner
Can we design mutations that bias proteins towards desired conformational states?
Today in @science.org, we introduce Conformational Biasing (CB), a simple and scalable computational method that uses contrastive scoring by inverse folding models to identify conformation-biasing mutations.
Today in @science.org, we introduce Conformational Biasing (CB), a simple and scalable computational method that uses contrastive scoring by inverse folding models to identify conformation-biasing mutations.
Computational design of conformation-biasing mutations to alter protein functions
Conformational biasing (CB) is a rapid and streamlined computational method that uses contrastive scoring by inverse folding models to predict protein variants biased toward desired conformational sta...
www.science.org
January 8, 2026 at 7:08 PM
Can we design mutations that bias proteins towards desired conformational states?
Today in @science.org, we introduce Conformational Biasing (CB), a simple and scalable computational method that uses contrastive scoring by inverse folding models to identify conformation-biasing mutations.
Today in @science.org, we introduce Conformational Biasing (CB), a simple and scalable computational method that uses contrastive scoring by inverse folding models to identify conformation-biasing mutations.
Reposted by Noah Holzleitner
1/ Check out our newest paper where we ask: How fast can we experimentally discover binders from scratch?
And we mean scratch: a blinded study.
TLDR: 26 days. And the binders work…and led to new cancer biology.
We’re coming for you AI….
chemrxiv.org/engage/chemr...
And we mean scratch: a blinded study.
TLDR: 26 days. And the binders work…and led to new cancer biology.
We’re coming for you AI….
chemrxiv.org/engage/chemr...
December 26, 2025 at 6:24 PM
1/ Check out our newest paper where we ask: How fast can we experimentally discover binders from scratch?
And we mean scratch: a blinded study.
TLDR: 26 days. And the binders work…and led to new cancer biology.
We’re coming for you AI….
chemrxiv.org/engage/chemr...
And we mean scratch: a blinded study.
TLDR: 26 days. And the binders work…and led to new cancer biology.
We’re coming for you AI….
chemrxiv.org/engage/chemr...
Reposted by Noah Holzleitner
✨New preprint!
🧵1/4 Excited to share our work on AI-guided design of minimal RNA-guided nucleases. Amazing work by @petrskopintsev.bsky.social @isabelesain.bsky.social @evandeturk.bsky.social et al!
Multi-lab collaboration @banfieldlab.bsky.social @jhdcate.bsky.social @jacobsenucla.bsky.social🧬
🔗👇
🧵1/4 Excited to share our work on AI-guided design of minimal RNA-guided nucleases. Amazing work by @petrskopintsev.bsky.social @isabelesain.bsky.social @evandeturk.bsky.social et al!
Multi-lab collaboration @banfieldlab.bsky.social @jhdcate.bsky.social @jacobsenucla.bsky.social🧬
🔗👇
December 9, 2025 at 7:52 AM
✨New preprint!
🧵1/4 Excited to share our work on AI-guided design of minimal RNA-guided nucleases. Amazing work by @petrskopintsev.bsky.social @isabelesain.bsky.social @evandeturk.bsky.social et al!
Multi-lab collaboration @banfieldlab.bsky.social @jhdcate.bsky.social @jacobsenucla.bsky.social🧬
🔗👇
🧵1/4 Excited to share our work on AI-guided design of minimal RNA-guided nucleases. Amazing work by @petrskopintsev.bsky.social @isabelesain.bsky.social @evandeturk.bsky.social et al!
Multi-lab collaboration @banfieldlab.bsky.social @jhdcate.bsky.social @jacobsenucla.bsky.social🧬
🔗👇
Reposted by Noah Holzleitner
Check out our newest work! This is a story on how to get selectivity in binders - both isoform and site selectivity. Read the paper or enjoy this brief Skytorial of what we did!
www.biorxiv.org/content/10.1...
1/n
www.biorxiv.org/content/10.1...
1/n
PANCS-spec-Binders: A system for rapidly discovering isoform- or epitope-specific binders
Proteins that bind to a target protein of interest, termed "binders," are essential components of biological research reagents and therapeutics. Target proteins present multiple binding surfaces with ...
www.biorxiv.org
November 19, 2025 at 6:10 PM
Check out our newest work! This is a story on how to get selectivity in binders - both isoform and site selectivity. Read the paper or enjoy this brief Skytorial of what we did!
www.biorxiv.org/content/10.1...
1/n
www.biorxiv.org/content/10.1...
1/n
Reposted by Noah Holzleitner
Our work developing a parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording is now out @natbiotech.nature.com
A parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording - @jshendure.bsky.social @troymcdiarmid.bsky.social @uwgenome.bsky.social go.nature.com/49eTPCu
A parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording - Nature Biotechnology
Prime editing in mammalian cells benefits from a comprehensive list of genetic parts.
go.nature.com
November 12, 2025 at 6:06 PM
Our work developing a parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording is now out @natbiotech.nature.com
Reposted by Noah Holzleitner
New preprint from
@gocastelobranco.bsky.social lab!! We use MPRA & scCRISPRi/a to interrogate possible functions of GWAS-identified Multiple sclerosis risk SNPs in iPSC-derived oligodendrocytes.
www.biorxiv.org/content/10.1...
@gocastelobranco.bsky.social lab!! We use MPRA & scCRISPRi/a to interrogate possible functions of GWAS-identified Multiple sclerosis risk SNPs in iPSC-derived oligodendrocytes.
www.biorxiv.org/content/10.1...
www.biorxiv.org
November 13, 2025 at 8:35 AM
New preprint from
@gocastelobranco.bsky.social lab!! We use MPRA & scCRISPRi/a to interrogate possible functions of GWAS-identified Multiple sclerosis risk SNPs in iPSC-derived oligodendrocytes.
www.biorxiv.org/content/10.1...
@gocastelobranco.bsky.social lab!! We use MPRA & scCRISPRi/a to interrogate possible functions of GWAS-identified Multiple sclerosis risk SNPs in iPSC-derived oligodendrocytes.
www.biorxiv.org/content/10.1...
Reposted by Noah Holzleitner
Fantastic Gioele!
🧠 The Lipid #Brain Atlas is out now! If you think #lipids are boring and membranes are all the same, prepare to be surprised. Led by @lucafusarbassini.bsky.social with Giovanni D'Angelo's lab, we mapped membrane lipids in the mouse brain at high resolution.
www.biorxiv.org/cgi/content/...
www.biorxiv.org/cgi/content/...
October 16, 2025 at 7:47 AM
Fantastic Gioele!
Super interesting! Love the “Turning an Art into Science” aspect 🧬
Our latest work seeks to answer a longstanding question: why is discovering new protein binders seemingly unpredictable – and can we better quantify and understand the de novo binder discover process? 1/12
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Mapping the diverse topologies of protein-protein interaction fitness landscapes
De novo binder discovery is unpredictable and inefficient due to a lack of quantitative understanding of protein-protein interaction (PPI) sequence-function landscapes. Here, we use our PANCS-Binder t...
www.biorxiv.org
October 15, 2025 at 6:52 PM
Super interesting! Love the “Turning an Art into Science” aspect 🧬
Reposted by Noah Holzleitner
Anyone from the Bio community already got their hands on a NVidia DGX Spark for structure prediction and Protein design workloads ?
October 15, 2025 at 5:43 AM
Anyone from the Bio community already got their hands on a NVidia DGX Spark for structure prediction and Protein design workloads ?
Reposted by Noah Holzleitner
Mapping the diverse topologies of protein-protein interaction fitness landscapes https://www.biorxiv.org/content/10.1101/2025.10.14.682342v1
October 15, 2025 at 3:03 AM
Mapping the diverse topologies of protein-protein interaction fitness landscapes https://www.biorxiv.org/content/10.1101/2025.10.14.682342v1
Reposted by Noah Holzleitner
Two group leader positions available in the broader areas of RNA science, RNA technologies, and RNA medicine. Attractive packages and a great environment. Come and join us at Helmholtz RNA Würzburg, Bavaria.
October 8, 2025 at 9:45 PM
Two group leader positions available in the broader areas of RNA science, RNA technologies, and RNA medicine. Attractive packages and a great environment. Come and join us at Helmholtz RNA Würzburg, Bavaria.