Luuk Loeff
@lloeff.bsky.social
Assistant Prof. at Leiden University Medical Center
Host-Defence | Structural biology | Single-molecule Biophysics
http://www.loefflab.com
Host-Defence | Structural biology | Single-molecule Biophysics
http://www.loefflab.com
Pinned
Luuk Loeff
@lloeff.bsky.social
· Dec 31
What a great way to end the year! ✨
Today in @cellpress.bsky.social we report the structure and function of the Shedu anti-phage defense system.
tinyurl.com/4crj6dnx
A long 🧵...
Today in @cellpress.bsky.social we report the structure and function of the Shedu anti-phage defense system.
tinyurl.com/4crj6dnx
A long 🧵...
Reposted by Luuk Loeff
Asgard archaea may have facilitated the evolutionary development of the mitochondria via endosymbiosis of α-proteobacteria at some point between the first eukaryotic common ancestor (FECA) and the last eukaryotic common ancestor (LECA)! 🧪
www.nature.com/articles/s41...
www.nature.com/articles/s41...
January 15, 2026 at 12:18 AM
Asgard archaea may have facilitated the evolutionary development of the mitochondria via endosymbiosis of α-proteobacteria at some point between the first eukaryotic common ancestor (FECA) and the last eukaryotic common ancestor (LECA)! 🧪
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Luuk Loeff
Happy to share our recent preprint:
"DNA-intercalating antiphage molecules trigger abortive infection through mutual destruction and synergize with bacterial immunity"
www.biorxiv.org/content/10.6...
@spp2330.bsky.social, @mibinet.bsky.social, @dfg.de @hhu.de @fzj.bsky.social
"DNA-intercalating antiphage molecules trigger abortive infection through mutual destruction and synergize with bacterial immunity"
www.biorxiv.org/content/10.6...
@spp2330.bsky.social, @mibinet.bsky.social, @dfg.de @hhu.de @fzj.bsky.social
January 14, 2026 at 8:57 AM
Happy to share our recent preprint:
"DNA-intercalating antiphage molecules trigger abortive infection through mutual destruction and synergize with bacterial immunity"
www.biorxiv.org/content/10.6...
@spp2330.bsky.social, @mibinet.bsky.social, @dfg.de @hhu.de @fzj.bsky.social
"DNA-intercalating antiphage molecules trigger abortive infection through mutual destruction and synergize with bacterial immunity"
www.biorxiv.org/content/10.6...
@spp2330.bsky.social, @mibinet.bsky.social, @dfg.de @hhu.de @fzj.bsky.social
Reposted by Luuk Loeff
🧫 🧪 We’re so excited to share our new preprint, where we tackle the wealth of structural and functional diversity across antiviral STAND NTPases in bacteria.
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
Diverse bacterial pattern recognition receptors sense the conserved phage proteome
Recognition of foreign molecules inside cells is critical for immunity in all domains of life. Proteins of the STAND NTPase superfamily, including eukaryotic nucleotide-binding oligomerization domain ...
www.biorxiv.org
January 6, 2026 at 1:19 AM
🧫 🧪 We’re so excited to share our new preprint, where we tackle the wealth of structural and functional diversity across antiviral STAND NTPases in bacteria.
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
Reposted by Luuk Loeff
NLR-like immunity in bacteria
A new study from the Alex Gao lab. The scope of this work is incredible!!!
www.biorxiv.org/content/10.6...
A new study from the Alex Gao lab. The scope of this work is incredible!!!
www.biorxiv.org/content/10.6...
Diverse bacterial pattern recognition receptors sense the conserved phage proteome
Recognition of foreign molecules inside cells is critical for immunity in all domains of life. Proteins of the STAND NTPase superfamily, including eukaryotic nucleotide-binding oligomerization domain ...
www.biorxiv.org
January 5, 2026 at 1:59 PM
NLR-like immunity in bacteria
A new study from the Alex Gao lab. The scope of this work is incredible!!!
www.biorxiv.org/content/10.6...
A new study from the Alex Gao lab. The scope of this work is incredible!!!
www.biorxiv.org/content/10.6...
Reposted by Luuk Loeff
Bacterial genomes encode a rich repertoire of antiphage systems, but we still know surprisingly little about when these systems are actually expressed.
In this preprint, Lucas Paoli et al, ask what shapes antiphage systems expression in native contexts.
www.biorxiv.org/content/10.6...
In this preprint, Lucas Paoli et al, ask what shapes antiphage systems expression in native contexts.
www.biorxiv.org/content/10.6...
Environment and physiology shape antiphage system expression
Bacteria and archaea encode on average ten antiphage systems. Quorum sensing, cellular, or transcription factors can regulate specific systems (CRISPR-Cas, CBASS). Yet, a systematic assessment of anti...
www.biorxiv.org
December 15, 2025 at 9:49 PM
Bacterial genomes encode a rich repertoire of antiphage systems, but we still know surprisingly little about when these systems are actually expressed.
In this preprint, Lucas Paoli et al, ask what shapes antiphage systems expression in native contexts.
www.biorxiv.org/content/10.6...
In this preprint, Lucas Paoli et al, ask what shapes antiphage systems expression in native contexts.
www.biorxiv.org/content/10.6...
Reposted by Luuk Loeff
Happy to share that I’m opening my lab at the Weizmann Institute of Science!
We’ll study systems-level regulation of bacterial defense, driven by RNA-protein interactions shaping cell fate.
Now recruiting PhD students & postdocs
tinyurl.com/4yfa55vd
Please reach out and share!
We’ll study systems-level regulation of bacterial defense, driven by RNA-protein interactions shaping cell fate.
Now recruiting PhD students & postdocs
tinyurl.com/4yfa55vd
Please reach out and share!
December 9, 2025 at 9:35 PM
Happy to share that I’m opening my lab at the Weizmann Institute of Science!
We’ll study systems-level regulation of bacterial defense, driven by RNA-protein interactions shaping cell fate.
Now recruiting PhD students & postdocs
tinyurl.com/4yfa55vd
Please reach out and share!
We’ll study systems-level regulation of bacterial defense, driven by RNA-protein interactions shaping cell fate.
Now recruiting PhD students & postdocs
tinyurl.com/4yfa55vd
Please reach out and share!
Reposted by Luuk Loeff
Exciting pre-print on new variants of anti-phage defense systems including CBASS, Pycsar, and Gabija!
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
Leveraging defense system modularity to discover anti-phage systems
Bacterial exposure to constant phage attack drives rapid diversification of anti-phage defense systems, often through the exchange of modular defensive domains. Here, we leverage this modularity signa...
www.biorxiv.org
December 9, 2025 at 7:25 PM
Exciting pre-print on new variants of anti-phage defense systems including CBASS, Pycsar, and Gabija!
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
Reposted by Luuk Loeff
✨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 Luuk Loeff
Phages are full of genes of unknown function that are likely adaptive in specific conditions.
New preprint: Phage TnSeq identifies essential genes rapidly and knocks all non-essentials. We would like to send a pool of phiKZ mutants to anyone wanting it! Reach out
tinyurl.com/bdcfrejh
New preprint: Phage TnSeq identifies essential genes rapidly and knocks all non-essentials. We would like to send a pool of phiKZ mutants to anyone wanting it! Reach out
tinyurl.com/bdcfrejh
December 8, 2025 at 3:04 PM
Phages are full of genes of unknown function that are likely adaptive in specific conditions.
New preprint: Phage TnSeq identifies essential genes rapidly and knocks all non-essentials. We would like to send a pool of phiKZ mutants to anyone wanting it! Reach out
tinyurl.com/bdcfrejh
New preprint: Phage TnSeq identifies essential genes rapidly and knocks all non-essentials. We would like to send a pool of phiKZ mutants to anyone wanting it! Reach out
tinyurl.com/bdcfrejh
Reposted by Luuk Loeff
Preprint: Systematic discovery of TIR-based immune signaling systems in bacteria
Conservation of TIR-derived signals accross the tree of life! We found bacterial TIR immune systems that signal via canonical cADPR (like in humans) and 2'cADPR (a plant immune signal).
Documented 11 Thoeris types
Conservation of TIR-derived signals accross the tree of life! We found bacterial TIR immune systems that signal via canonical cADPR (like in humans) and 2'cADPR (a plant immune signal).
Documented 11 Thoeris types
December 4, 2025 at 1:56 PM
Preprint: Systematic discovery of TIR-based immune signaling systems in bacteria
Conservation of TIR-derived signals accross the tree of life! We found bacterial TIR immune systems that signal via canonical cADPR (like in humans) and 2'cADPR (a plant immune signal).
Documented 11 Thoeris types
Conservation of TIR-derived signals accross the tree of life! We found bacterial TIR immune systems that signal via canonical cADPR (like in humans) and 2'cADPR (a plant immune signal).
Documented 11 Thoeris types
Reposted by Luuk Loeff
I’m happy to share our new preprint! We uncovered the full diversity of bacterial TIR-based antiviral immune signaling, massively expanded the known diversity of Thoeris systems, and revealed conservation of TIR-derived immune signals across the tree of life.
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
Systematic discovery of TIR-based immune signaling systems in bacteria
Toll/interleukin-1 receptor (TIR) domains are important for immune signaling across humans, plants and bacteria. These domains were recently found to produce immune signaling molecules in plant immuni...
www.biorxiv.org
December 4, 2025 at 9:25 AM
I’m happy to share our new preprint! We uncovered the full diversity of bacterial TIR-based antiviral immune signaling, massively expanded the known diversity of Thoeris systems, and revealed conservation of TIR-derived immune signals across the tree of life.
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
Reposted by Luuk Loeff
Check this out for the 2026 SISB (phage defense) meeting in NYC. Mark your calendar! (and note the Zoom option, if needed)
sisb2026.rockefeller.edu
sisb2026.rockefeller.edu
SISB2026
sisb2026.rockefeller.edu
December 1, 2025 at 11:44 PM
Check this out for the 2026 SISB (phage defense) meeting in NYC. Mark your calendar! (and note the Zoom option, if needed)
sisb2026.rockefeller.edu
sisb2026.rockefeller.edu
Reposted by Luuk Loeff
🧬🛡️How are new immune mechanisms created?
We show how Lamassu antiphage system, originated from a DNA-repair complex and evolved into a compact and modular immune machine, wt Dinshaw Patel lab in @pnas.org.
👏 @matthieu-haudiquet.bsky.social, Arpita Chakravarti & all authors!
doi.org/10.1073/pnas...
We show how Lamassu antiphage system, originated from a DNA-repair complex and evolved into a compact and modular immune machine, wt Dinshaw Patel lab in @pnas.org.
👏 @matthieu-haudiquet.bsky.social, Arpita Chakravarti & all authors!
doi.org/10.1073/pnas...
November 27, 2025 at 9:35 AM
🧬🛡️How are new immune mechanisms created?
We show how Lamassu antiphage system, originated from a DNA-repair complex and evolved into a compact and modular immune machine, wt Dinshaw Patel lab in @pnas.org.
👏 @matthieu-haudiquet.bsky.social, Arpita Chakravarti & all authors!
doi.org/10.1073/pnas...
We show how Lamassu antiphage system, originated from a DNA-repair complex and evolved into a compact and modular immune machine, wt Dinshaw Patel lab in @pnas.org.
👏 @matthieu-haudiquet.bsky.social, Arpita Chakravarti & all authors!
doi.org/10.1073/pnas...
Reposted by Luuk Loeff
The hinge bypass gate paper is finally out! doi.org/10.1038/s414...
We show how loop-extruding SMC complexes can maintain DNA entrapment while bypassing obstacles on DNA — including transcription machinery & potentially other SMCs.
A lucky convergence of 3 projects lead to the initial discovery!
We show how loop-extruding SMC complexes can maintain DNA entrapment while bypassing obstacles on DNA — including transcription machinery & potentially other SMCs.
A lucky convergence of 3 projects lead to the initial discovery!
The SMC Hinge is a Selective Gate for Obstacle Bypass - Nature Communications
SMC complexes are ring-shaped motors that fold DNA by extruding loops, but how they navigate large DNA obstacles is unclear. Here, Liu et al., show that SMC complexes bypass obstacles by threading obs...
doi.org
November 25, 2025 at 3:26 PM
The hinge bypass gate paper is finally out! doi.org/10.1038/s414...
We show how loop-extruding SMC complexes can maintain DNA entrapment while bypassing obstacles on DNA — including transcription machinery & potentially other SMCs.
A lucky convergence of 3 projects lead to the initial discovery!
We show how loop-extruding SMC complexes can maintain DNA entrapment while bypassing obstacles on DNA — including transcription machinery & potentially other SMCs.
A lucky convergence of 3 projects lead to the initial discovery!
Reposted by Luuk Loeff
Hot off the press! Our latest paper led by @fernpizza.bsky.social, understanding how plasmids evolve inside cells. These small, self-replicating DNA circles live inside bacteria and carry antibiotic resistance genes, but also compete with one another to replicate. 1/
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Intracellular competition shapes plasmid population dynamics
From populations of multicellular organisms to selfish genetic elements, conflicts between levels of biological organization are central to evolution. Plasmids are extrachromosomal, self-replicating g...
www.science.org
November 20, 2025 at 9:42 PM
Hot off the press! Our latest paper led by @fernpizza.bsky.social, understanding how plasmids evolve inside cells. These small, self-replicating DNA circles live inside bacteria and carry antibiotic resistance genes, but also compete with one another to replicate. 1/
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Reposted by Luuk Loeff
🚨Preprint alert - this is a big one! We transfer the revolutionary power of TnSeq to bacteriophages.
Our HIDEN-SEQ links the "dark matter" genes of your favorite phage to any selectable phenotype, guiding the path from fun observations to molecular mechanisms.
A thread 1/8
Our HIDEN-SEQ links the "dark matter" genes of your favorite phage to any selectable phenotype, guiding the path from fun observations to molecular mechanisms.
A thread 1/8
November 20, 2025 at 8:40 PM
🚨Preprint alert - this is a big one! We transfer the revolutionary power of TnSeq to bacteriophages.
Our HIDEN-SEQ links the "dark matter" genes of your favorite phage to any selectable phenotype, guiding the path from fun observations to molecular mechanisms.
A thread 1/8
Our HIDEN-SEQ links the "dark matter" genes of your favorite phage to any selectable phenotype, guiding the path from fun observations to molecular mechanisms.
A thread 1/8
Reposted by Luuk Loeff
Very excited to share our latest work in Science on metagenomic editing (MetaEdit) of the gut microbiome in vivo & directly modifying unculturable immune-modulatory SFB bug in the small intestine. 🦠🧬🛠️
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Metagenomic editing of commensal bacteria in vivo using CRISPR-associated transposases
Although metagenomic sequencing has revealed a rich microbial biodiversity in the mammalian gut, methods to genetically alter specific species in the microbiome are highly limited. Here, we introduce ...
www.science.org
November 13, 2025 at 8:53 PM
Very excited to share our latest work in Science on metagenomic editing (MetaEdit) of the gut microbiome in vivo & directly modifying unculturable immune-modulatory SFB bug in the small intestine. 🦠🧬🛠️
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Reposted by Luuk Loeff
1/9 Metagenomics lets us read microbiomes in nature without cultivation, but writing (editing) them in their native context is still a major challenge.
Meet MetaEdit: a platform for pathway-scale metagenomic editing inside the gut microbiome. science.org/doi/10.1126/...
Meet MetaEdit: a platform for pathway-scale metagenomic editing inside the gut microbiome. science.org/doi/10.1126/...
Metagenomic editing of commensal bacteria in vivo using CRISPR-associated transposases
Although metagenomic sequencing has revealed a rich microbial biodiversity in the mammalian gut, methods to genetically alter specific species in the microbiome are highly limited. Here, we introduce ...
science.org
November 14, 2025 at 2:25 PM
1/9 Metagenomics lets us read microbiomes in nature without cultivation, but writing (editing) them in their native context is still a major challenge.
Meet MetaEdit: a platform for pathway-scale metagenomic editing inside the gut microbiome. science.org/doi/10.1126/...
Meet MetaEdit: a platform for pathway-scale metagenomic editing inside the gut microbiome. science.org/doi/10.1126/...
Reposted by Luuk Loeff
Our nuclease-protease story is out! We explored a fascinating case of coevolution and modularity in prokaryotic immune systems: www.science.org/doi/10.1126/...
Thanks to wonderful coauthors/collaborators/friends, the whole @doudna-lab.bsky.social and everyone at @innovativegenomics.bsky.social
Thanks to wonderful coauthors/collaborators/friends, the whole @doudna-lab.bsky.social and everyone at @innovativegenomics.bsky.social
Recurrent acquisition of nuclease-protease pairs in antiviral immunity
Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin...
www.science.org
November 13, 2025 at 10:15 PM
Our nuclease-protease story is out! We explored a fascinating case of coevolution and modularity in prokaryotic immune systems: www.science.org/doi/10.1126/...
Thanks to wonderful coauthors/collaborators/friends, the whole @doudna-lab.bsky.social and everyone at @innovativegenomics.bsky.social
Thanks to wonderful coauthors/collaborators/friends, the whole @doudna-lab.bsky.social and everyone at @innovativegenomics.bsky.social
Reposted by Luuk Loeff
Gluing a bulky host protein onto an immune surveillance complex is a wild mechanism of viral immune evasion!
@natmicrobiol.nature.com
#phagesky #phage #microsky
www.nature.com/articles/s41...
@natmicrobiol.nature.com
#phagesky #phage #microsky
www.nature.com/articles/s41...
November 12, 2025 at 5:47 PM
Gluing a bulky host protein onto an immune surveillance complex is a wild mechanism of viral immune evasion!
@natmicrobiol.nature.com
#phagesky #phage #microsky
www.nature.com/articles/s41...
@natmicrobiol.nature.com
#phagesky #phage #microsky
www.nature.com/articles/s41...
Cool work by the @soreklab.bsky.social laboratory. Metis detects host-genome degradation by sensing the accumulation of methylated deoxy-adenosines. Subsequently, triggering its immune response. Very elegant mechanism! Congrats to all involved!
Bacteria can sense when a virus starts shredding their genome — by detecting methylated mononucleotides.
Here’s the story of how we discovered the Metis defense system 👇
www.biorxiv.org/content/10.1...
Here’s the story of how we discovered the Metis defense system 👇
www.biorxiv.org/content/10.1...
November 6, 2025 at 8:18 AM
Cool work by the @soreklab.bsky.social laboratory. Metis detects host-genome degradation by sensing the accumulation of methylated deoxy-adenosines. Subsequently, triggering its immune response. Very elegant mechanism! Congrats to all involved!
Huge news for the Dutch structural biology community! NWO is investing €33 million to modernize the national cryo-EM infrastructure (EMPower). Exciting times ahead!
www.nwo.nl/en/news/nati...
www.nwo.nl/en/news/nati...
National Roadmap: NWO invests 197 million euro in eleven Large-Scale Research Infrastructures | NWO
Eleven consortia from various scientific disciplines are set to launch projects of great value to science. But also to the economic and social prosperity of the Netherlands. For example, a consortium led by TU Delft will start work on a detailed virtual model of the Dutch energy system. In another project, a consortium of UMC Utrecht is developing an MRI scanner that can scan people in motion.
www.nwo.nl
November 4, 2025 at 10:45 AM
Huge news for the Dutch structural biology community! NWO is investing €33 million to modernize the national cryo-EM infrastructure (EMPower). Exciting times ahead!
www.nwo.nl/en/news/nati...
www.nwo.nl/en/news/nati...
Reposted by Luuk Loeff
Last year it was discovered that a single bacterial NLR-like protein can recognize multiple, structurally unrelated phage proteins (Béchon et al, Kibby et al)
Now, a new study shows the same for a plant NLR. Another example how principles of immunity remain conserved from bacteria to eukaryotes
Now, a new study shows the same for a plant NLR. Another example how principles of immunity remain conserved from bacteria to eukaryotes
A wheat NLR conferring broad-spectrum resistance against powdery mildew by recognizing two structurally diverse AVR effectors. Interested? Check out our newest preprint: www.biorxiv.org/content/10.1...
Dual recognition of structurally unrelated mildew effectors underlies the broad-spectrum resistance of Pm3e in wheat
Broad-spectrum resistance genes are highly valuable for sustainable crop protection, yet the molecular basis of their activity is often unknown. The Pm3 allelic series in wheat encodes NLR receptors t...
www.biorxiv.org
November 2, 2025 at 6:34 PM
Last year it was discovered that a single bacterial NLR-like protein can recognize multiple, structurally unrelated phage proteins (Béchon et al, Kibby et al)
Now, a new study shows the same for a plant NLR. Another example how principles of immunity remain conserved from bacteria to eukaryotes
Now, a new study shows the same for a plant NLR. Another example how principles of immunity remain conserved from bacteria to eukaryotes
Reposted by Luuk Loeff
On that note: hello world! My new lab on genetics of proteome remodeling is starting at the incredible MPI-CBG. We have big plans and open positions for PhD students and an RA. Apply now (!) at imprs.mpi-cbg.de and tinyurl.com/2vywj6f6 respectively.
October 21, 2025 at 9:53 PM
On that note: hello world! My new lab on genetics of proteome remodeling is starting at the incredible MPI-CBG. We have big plans and open positions for PhD students and an RA. Apply now (!) at imprs.mpi-cbg.de and tinyurl.com/2vywj6f6 respectively.
Reposted by Luuk Loeff
Glad to share our paper out today @NatureEcoEvo: “Serial innovations by Asgard archaea shaped the DNA replication machinery of the early eukaryotic ancestor”. www.nature.com/articles/s41... #microsky #archaeasky
Serial innovations by Asgard archaea shaped the DNA replication machinery of the early eukaryotic ancestor - Nature Ecology & Evolution
Phylogenetic and biochemical analyses show a diversity of components of the DNA replication machinery in different Asgard archaea that contributed to the eukaryotic DNA replication machinery.
www.nature.com
October 21, 2025 at 3:06 PM
Glad to share our paper out today @NatureEcoEvo: “Serial innovations by Asgard archaea shaped the DNA replication machinery of the early eukaryotic ancestor”. www.nature.com/articles/s41... #microsky #archaeasky