Luuk Loeff
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lloeff.bsky.social
Luuk Loeff
@lloeff.bsky.social
Assistant Prof. at Leiden University Medical Center

Host-Defence | Structural biology | Single-molecule Biophysics

http://www.loefflab.com
Pinned
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 🧵...
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/...
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
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
November 20, 2025 at 8:40 PM
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/...
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
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/...
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
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
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
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...
November 12, 2025 at 5:47 PM
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...
November 6, 2025 at 8:18 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...
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
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
November 2, 2025 at 6:34 PM
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
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
Reposted by Luuk Loeff
1/10 Genome maintenance by telomerase is a fundamental process in nearly all eukaryotes. But where does it come from?

Today, we report the discovery of telomerase homologs in a family of antiviral RTs, revealing an unexpected evolutionary origin in bacteria.
www.biorxiv.org/content/10.1...
Antiviral reverse transcriptases reveal the evolutionary origin of telomerase
Defense-associated reverse transcriptases (DRTs) employ diverse and distinctive mechanisms of cDNA synthesis to protect bacteria against viral infection. However, much of DRT family diversity remains ...
www.biorxiv.org
October 17, 2025 at 5:22 PM
One week left to apply!!
Hiring! 🧬🔬

Ever wondered how bacteria fight off viruses? We’re looking for a PhD student to dive into the molecular basis of newly discovered microbial immune systems, an area of biology where much remains to be uncovered.

RT/share to help us find our next team member!
www.lumc.nl/en/about-lum...
PhD-positie Bacteriële Verdedigingssystemen tegen Virussen | LUMC
Wij zoeken een getalenteerde en gemotiveerde PhD-kandidaat om het onderzoeksteam van Luuk Loeff te versterken. In dit project maak je gebruik van geavanceerde technologieën om te ontrafelen hoe bacter...
www.lumc.nl
October 10, 2025 at 10:36 AM
Reposted by Luuk Loeff
How do SMC complexes load onto DNA to get ready for loop extrusion?

@roisnehamelinf.bsky.social & co discovered that Wadjet, an SMC complex involved in bacterial DNA immunity, performs some impressive molecular gymnastics 🤸‍♂️🤸‍♂️🤸‍♂️.

Check out the new paper: www.cell.com/molecular-ce...
October 9, 2025 at 2:43 PM
Reposted by Luuk Loeff
Today in @nature.com , we highlight how a cousin of CRISPR-Cas10, mCpol, establishes an evolutionary trap in anti-phage immune systems.

Check out @erinedoherty.bsky.social and my work from @doudna-lab.bsky.social lab here:
www.nature.com/articles/s41...
A miniature CRISPR–Cas10 enzyme confers immunity by inhibitory signalling - Nature
Panoptes, an anti-phage defence system against virus-mediated immune suppression, is revealed.
www.nature.com
October 1, 2025 at 5:57 PM
Reposted by Luuk Loeff
Our story describing the Panoptes bacterial immune defense system is now finally peer-reviewed and published today! www.nature.com/articles/s41...
The Panoptes system uses decoy cyclic nucleotides to defend against phage - Nature
The Panoptes antiphage system defends bacteria by detecting phage-encoded counter-defences that sequester cyclic nucleotide signals, triggering membrane disruption and highlighting a broader strategy of sensing immune evasion through second-messenger surveillance.
www.nature.com
October 1, 2025 at 4:05 PM
Hiring! 🧬🔬

Ever wondered how bacteria fight off viruses? We’re looking for a PhD student to dive into the molecular basis of newly discovered microbial immune systems, an area of biology where much remains to be uncovered.

RT/share to help us find our next team member!
www.lumc.nl/en/about-lum...
PhD-positie Bacteriële Verdedigingssystemen tegen Virussen | LUMC
Wij zoeken een getalenteerde en gemotiveerde PhD-kandidaat om het onderzoeksteam van Luuk Loeff te versterken. In dit project maak je gebruik van geavanceerde technologieën om te ontrafelen hoe bacter...
www.lumc.nl
September 29, 2025 at 11:36 AM
Reposted by Luuk Loeff
You’ve heard of ubiquitination, meet deazaguanylation: Doug Wassarman in our lab discovered phage defense pathways have co-opted Q nucleobase biosynthetic enzymes to catalyze a new form of protein conjugation chemistry @science.org

www.science.org/doi/10.1126/...
September 25, 2025 at 7:16 PM
Reposted by Luuk Loeff
Coming up next week: the third Dutch Structural Biology meeting! Now in Delft, on Sept 26. See program here: nvbmb.kncv.nl/biology-2025 with #teamtomo #cryoEM #nmrchat simulations and more (looks like)

Organized by the #NVBMB (associated with KNCV)
Dutch Structural Biology Meeting 2025 - NVBMB
nvbmb.kncv.nl
September 18, 2025 at 9:02 PM
Reposted by Luuk Loeff
Spacedust: a tool for de novo identification of conserved gene clusters from metagenomic data.
@ruoshiz.bsky.social @milot.bsky.social

www.nature.com/articles/s41...
De novo discovery of conserved gene clusters in microbial genomes with Spacedust - Nature Methods
This work presents Spacedust, a tool for de novo identification of conserved gene clusters from metagenomic data.
www.nature.com
September 16, 2025 at 1:25 PM
Reposted by Luuk Loeff
🚀 New publication alert! 🚀

We just published in @natbiotech.nature.com:
👉 Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes
doi.org/10.1038/s415...
Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes - Nature Biotechnology
Append editing of ADP-ribosyl to thymine is used for precise modifications in bacteria and eukaryotes.
doi.org
September 4, 2025 at 6:51 PM
Reposted by Luuk Loeff
Excited to share my latest review, now published in the Royal Society theme issue on ‘The ecology and evolution of bacterial immune systems' (available OA):

Defence systems encoded by core genomic islands of seventh pandemic Vibrio cholerae royalsocietypublishing.org/doi/10.1098/...
Defence systems encoded by core genomic islands of seventh pandemic Vibrio cholerae | Philosophical Transactions of the Royal Society B: Biological Sciences
Vibrio cholerae, the causative agent of cholera, has triggered seven pandemics, with the seventh pandemic emerging in 1961. The success of seventh pandemic El Tor (7PET) V. cholerae as a human pathogen is linked to its acquisition of mobile genetic ...
royalsocietypublishing.org
September 6, 2025 at 1:02 PM
Reposted by Luuk Loeff
How can we understand the earliest events in evolution of eukaryotic immunity? @yao-li.bsky.social reports incredible molecular fossils of complete bacterial-like operons in eukaryotes that illuminate how animal immunity was first acquired from anti-phage defense

www.biorxiv.org/content/10.1...
September 5, 2025 at 10:13 AM
Reposted by Luuk Loeff
Our Wadjet-II paper by @roisnehamelinf.bsky.social is out in polished form: www.cell.com/structure/fu...

With a great preview by @kevincorbett.bsky.social & @amardeeep.bsky.social highlighting the potential of Wadjets:

Wadjet—Keeping a watchful eye on circular DNA.

www.cell.com/structure/fu...
September 5, 2025 at 6:29 AM
Reposted by Luuk Loeff
Preprint: De-novo design of proteins that inhibit bacterial defenses

Our approach allows silencing defense systems of choice. We show how this approach enables programming of “untransformable” bacteria, and how it can enhance phage therapy applications

Congrats Jeremy Garb!
tinyurl.com/Syttt
🧵
Synthetically designed anti-defense proteins overcome barriers to bacterial transformation and phage infection
Bacterial defense systems present considerable barriers to both phage infection and plasmid transformation. These systems target mobile genetic elements, limiting the efficacy of bacteriophage-based t...
www.biorxiv.org
September 2, 2025 at 10:48 AM