Luuk Loeff's Avatar

Luuk Loeff

@lloeff.bsky.social

Assistant Prof. at Leiden University Medical Center Host-Defence | Structural biology | Single-molecule Biophysics http://www.loefflab.com

1,295 Followers  |  238 Following  |  107 Posts  |  Joined: 11.12.2023  |  2.1037

Latest posts by lloeff.bsky.social on Bluesky

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Amazing findings in geometry-based immune activation! Two bacterial defence systems detect phage-encoded ring oligomers, assemble high-order molecular complexes, and trigger abortive infection.

www.nature.com/articles/s41...
www.nature.com/articles/s41...

04.02.2026 18:24 β€” πŸ‘ 22    πŸ” 10    πŸ’¬ 1    πŸ“Œ 0
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Chemical inhibition of a bacterial immune system Bacteriophages are promising alternatives to antibiotics for treating bacterial infections. However, bacteria possess immune systems that neutralize bacteriophages. Zang et al. discover small molecule...

Really phenomenal work from the Gerdt lab at Indiana University... I hope this becomes a major boon for phage therapy:
"Chemical inhibition of a bacterial immune system"
www.cell.com/cell-host-mi...

31.01.2026 01:54 β€” πŸ‘ 10    πŸ” 5    πŸ’¬ 0    πŸ“Œ 0
Bacterial defense via RES-mediated NAD+ depletion is countered by phage phosphatases Many bacterial defense systems restrict phage infection by breaking the molecule NAD+ to its constituents, adenosine diphosphate ribose (ADPR) and nicotinamide (Nam). To counter NAD+ depletion-mediated defense, phages evolved NAD+ reconstitution pathway 1 (NARP1), which uses ADPR and Nam to rebuild NAD+. Here we report a bacterial defense system called aRES, involving RES-domain proteins that degrade NAD+ into Nam and ADPR-1β€³-phosphate (ADPR-1P). This molecule cannot serve as a substrate for NARP1, so that NAD+ depletion by aRES defends against phages even if they encode NARP1. We further discover that some phages evolved an extended NARP1 pathway capable of overcoming aRES defense. In these phages, the NARP1 operon also includes a specialized phosphatase, which dephosphorylates ADPR-1P to form ADPR, a substrate from which NARP1 then reconstitutes NAD+. Other phages encode inhibitors that directly bind aRES proteins and physically block their active sites. Our study describes new layers in the NAD+-centric arms race between bacteria and phages and highlights the centrality of the NAD+ pool in cellular battles between viruses and their hosts. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, ERC-AdG GA 101018520 Israel Science Foundation, MAPATS grant 2720/22 Deutsche Forschungsgemeinschaft, SPP 2330, grant 464312965 Minerva Foundation with funding from the Federal German Ministry for Education and Research research grant from Magnus Konow in honor of his mother Olga Konow Rappaport Ministry of Aliyah and Immigrant Absorption, https://ror.org/05aycsg86 Clore Scholars Program

We found a new mode by which bacteria deplete NAD+ to protect from phages. And then we found how phages overcome this defense

Discovered by talented biochemist Dr Ilya Osterman, read the preprint: tinyurl.com/Narp-ap

A thread 🧡

29.01.2026 15:34 β€” πŸ‘ 43    πŸ” 15    πŸ’¬ 2    πŸ“Œ 0
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A prophage-encoded abortive infection protein preserves host and prophage spread - Nature A Gifsy-1 prophage–encoded higher eukaryotes and prokaryotes nucleotide-binding protein, HepS, senses Siphoviridae infection, activates abortive defence by cleaving host transfer RNAs, blocks rival ph...

A prophage-encoded abortive infection protein preserves host and prophage spread www.nature.com/articles/s41...

28.01.2026 19:13 β€” πŸ‘ 42    πŸ” 20    πŸ’¬ 0    πŸ“Œ 2
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Postdoctoral position - Synthetic Biology / Bacterial Immunity - Research The Bikard lab at Institut Pasteur in Paris is seeking to hire postdoctoral researchers. We are investigating bacteria / bacteriophages interactions, and the genetic innovation that happens at this in...

🚨 Hiring Alert! 🚨My lab at Institut Pasteur is recruiting several Postdocs! We have exciting open projects in: 🦠 Synthetic Biology andπŸ›‘οΈ Bacterial Immunity. Come do great science with us in the middle of Paris! πŸ‡«πŸ‡·πŸ₯ research.pasteur.fr/en/job/postd...

28.01.2026 11:19 β€” πŸ‘ 59    πŸ” 60    πŸ’¬ 0    πŸ“Œ 0
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Bacteriophages mobilize bacterial defense systems via lateral transduction Bacteriophages and PICIs spread bacterial defenses via lateral transduction, shaping microbial immunity and pathogen evolution.

@jakob-tr.bsky.social @jrpenades.bsky.social et al. πŸ”₯!

www.science.org/doi/10.1126/...

24.01.2026 13:22 β€” πŸ‘ 13    πŸ” 5    πŸ’¬ 0    πŸ“Œ 0
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Hello world! I am excited to announce my lab is open at the University of Utah in the Department of Biochemistry. We are looking for scientists at all levels interested in studying host-virus interactions in both bacteria and animals. Come join us in beautiful Utah! (photo is 10 steps from lab)

22.01.2026 22:06 β€” πŸ‘ 72    πŸ” 31    πŸ’¬ 6    πŸ“Œ 0
A methylome-derived m6-dAMP trigger assembles a PUA-Cal-HAD immune filament that depletes dNTPs to abort phage infection Bacteria must distinguish phage attack from normal homeostatic processes, yet the danger signals that trigger many defence systems remain unknown. Here, we show that a PUA-Calcineurin-CE-HAD module from Escherichia coli ECOR28 confers broad anti-phage protection by binding Dam-methylated deoxyadenosine monophosphate (m6-dAMP) generated during phage-induced chromosome degradation. Ligand binding converts a preassembled PUA-Calcineurin-CE hexamer loaded with six HAD phosphatases into a polymerising filament. The filament acts as a high-flux dNTP sink through a two-enzyme cascade: HAD first dephosphorylates dATP to dADP, and Calcineurin-CE then converts dADP to dAMP. dNTP collapse halts phage replication and enforces abortive infection. Multiple mobile-element DNA mimic proteins block filament assembly, revealing a direct phage counter-defence. More broadly, our findings extend a conserved, cross-kingdom paradigm of immune filament assembly to nucleotide-depletion antiviral defence and suggest modified-nucleotide sensing by related PUA-Calcineurin-CE modules as a widespread, underappreciated bacterial strategy. ### Competing Interest Statement The authors have declared no competing interest. NIHR Southampton Biomedical Research Centre, https://ror.org/01qqpzg67, Postdoctoral Bridging Fellowship F.L.N. is supported by a Wessex Health Partners (WHP) and National Institute for Health and Care Research Wessex Experimental Medicine Network (NIHR WEMN), Seed fund National Institutes of Health, GM145888, U24 GM129539) Maloris Foundation Memorial Sloan Kettering Cancer Center, P30-CA008748 Simons Foundation, SF349247 New York State Assembly

Preprint out: We characterise PUA-Cal-HAD, a widespread bacterial antiphage defence family. An infection cue switches a preassembled complex into an immune filament that drains dNTPs via a coupled two-enzyme cascade, and phage DNA mimics can block filament assembly (anti-polymerisation).

17.01.2026 14:52 β€” πŸ‘ 34    πŸ” 19    πŸ’¬ 1    πŸ“Œ 0
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A phage protein screen identifies triggers of the bacterial innate immune system Nature Microbiology, Published online: 16 January 2026; doi:10.1038/s41564-025-02239-6A library of 400 phage protein-coding genes is used to find a trove of antiphage systems, revealing systems that target tail fibre and major capsid proteins.

Out Now! A phage protein screen identifies triggers of the bacterial innate immune system #MicroSky

16.01.2026 16:53 β€” πŸ‘ 46    πŸ” 28    πŸ’¬ 0    πŸ“Œ 2
Illustration of gene flow along the succession of events leading from a simple archaeal ancestor through the more complex Asgard intermediate capturing the proto-mitochondrial alphaproteobacterial endosymbiont to the LECA. The wide coloured shape denotes the dominant trend of the origin of eukaryotic genes from Asgard ancestors, with light blue portions corresponding to archaeal evolution and the light brown portion to the evolution of protoeukaryotes starting with the alphaproteobacterial endosymbiosis. The purple arrows denote the smaller, piecemeal contributions of gene influx from various bacteria that are posited to have been occurring at all stages of the depicted evolutionary scenario.

Illustration of gene flow along the succession of events leading from a simple archaeal ancestor through the more complex Asgard intermediate capturing the proto-mitochondrial alphaproteobacterial endosymbiont to the LECA. The wide coloured shape denotes the dominant trend of the origin of eukaryotic genes from Asgard ancestors, with light blue portions corresponding to archaeal evolution and the light brown portion to the evolution of protoeukaryotes starting with the alphaproteobacterial endosymbiosis. The purple arrows denote the smaller, piecemeal contributions of gene influx from various bacteria that are posited to have been occurring at all stages of the depicted evolutionary scenario.

Asgard archaea may have facilitated the evolutionary development of the mitochondria via endosymbiosis of Ξ±-proteobacteria at some point between the first eukaryotic common ancestor (FECA) and the last eukaryotic common ancestor (LECA)! πŸ§ͺ

www.nature.com/articles/s41...

15.01.2026 00:18 β€” πŸ‘ 30    πŸ” 14    πŸ’¬ 1    πŸ“Œ 1

Many congratulations Martijn!

15.01.2026 08:17 β€” πŸ‘ 0    πŸ” 0    πŸ’¬ 1    πŸ“Œ 1

Many congratulations Francois and well deserved!

14.01.2026 15:39 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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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

14.01.2026 08:57 β€” πŸ‘ 43    πŸ” 26    πŸ’¬ 2    πŸ“Œ 0
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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 ...

🧫 πŸ§ͺ 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...

06.01.2026 01:20 β€” πŸ‘ 32    πŸ” 12    πŸ’¬ 0    πŸ“Œ 0
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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 ...

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...

05.01.2026 13:59 β€” πŸ‘ 59    πŸ” 34    πŸ’¬ 0    πŸ“Œ 1
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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...

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...

15.12.2025 21:48 β€” πŸ‘ 98    πŸ” 49    πŸ’¬ 2    πŸ“Œ 0

Many congratulations Shai!!

11.12.2025 19:22 β€” πŸ‘ 0    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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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!

09.12.2025 21:35 β€” πŸ‘ 21    πŸ” 15    πŸ’¬ 2    πŸ“Œ 0
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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...

Exciting pre-print on new variants of anti-phage defense systems including CBASS, Pycsar, and Gabija!

www.biorxiv.org/content/10.6...

09.12.2025 19:25 β€” πŸ‘ 21    πŸ” 4    πŸ’¬ 0    πŸ“Œ 0
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✨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🧬

πŸ”—πŸ‘‡

09.12.2025 07:52 β€” πŸ‘ 98    πŸ” 47    πŸ’¬ 1    πŸ“Œ 8
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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

08.12.2025 15:04 β€” πŸ‘ 90    πŸ” 42    πŸ’¬ 2    πŸ“Œ 2

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

04.12.2025 13:56 β€” πŸ‘ 34    πŸ” 13    πŸ’¬ 1    πŸ“Œ 0
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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...

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...

04.12.2025 09:24 β€” πŸ‘ 74    πŸ” 29    πŸ’¬ 2    πŸ“Œ 7
SISB2026

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

01.12.2025 23:44 β€” πŸ‘ 35    πŸ” 19    πŸ’¬ 0    πŸ“Œ 5
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πŸ§¬πŸ›‘οΈ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.
πŸ‘ @matthieu-haudiquet.bsky.social, Arpita Chakravarti & all authors!

doi.org/10.1073/pnas...

27.11.2025 09:35 β€” πŸ‘ 104    πŸ” 47    πŸ’¬ 1    πŸ“Œ 2
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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...

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 β€” including transcription machinery & potentially other SMCs.

A lucky convergence of 3 projects lead to the initial discovery!

25.11.2025 15:26 β€” πŸ‘ 31    πŸ” 15    πŸ’¬ 1    πŸ“Œ 2
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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...

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/...

20.11.2025 21:42 β€” πŸ‘ 436    πŸ” 200    πŸ’¬ 11    πŸ“Œ 18

Congrats @aharms485.bsky.social and @humollidorentina.bsky.social, very cool method!

21.11.2025 14:33 β€” πŸ‘ 4    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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🚨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

20.11.2025 20:39 β€” πŸ‘ 210    πŸ” 90    πŸ’¬ 11    πŸ“Œ 5
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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 ...

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. πŸ¦ πŸ§¬πŸ› οΈ
www.science.org/doi/10.1126/...

13.11.2025 20:53 β€” πŸ‘ 73    πŸ” 33    πŸ’¬ 2    πŸ“Œ 0

@lloeff is following 20 prominent accounts