Luuk Loeff

Luuk Loeff

@lloeff.bsky.social

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

1.3K followers261 following164 posts

Luuk Loeff reposted

Luuk Loeff reposted

Thrilled to be among this year’s NWO Vidi laureates! Really excited to expand our work on how coronaviruses control spike opening during cell entry, using #cryoEM and more. Keep an eye out for postdoc positions in the not-too-distant future. www.nwo.nl/en/news/109-...

nwo.nl109 Vidi grants awarded to talented researchers | NWONWO has awarded Vidi funding of up to 850,000 euros to no fewer than 109 researchers from the scientific fields of domain Science (ENW), Applied and Technical Sciences (AES), Social Sciences and Human...

Luuk Loeff reposted

Thrilled to announce that I have received the Vidi grant from the Dutch Research Council (NWO). This will enable my young lab to grow! For a period of five year, we will investigate how actin filaments interact with proteins at the membrane to drive cell adhesion. www.nwo.nl/en/news/109-...

nwo.nl109 Vidi grants awarded to talented researchers | NWONWO has awarded Vidi funding of up to 850,000 euros to no fewer than 109 researchers from the scientific fields of domain Science (ENW), Applied and Technical Sciences (AES), Social Sciences and Human...

Very happy to share that I've been awarded an NWO Vidi grant! Excited for the opportunity to expand our lab and continue investigating the molecular arms race between bacteria and their viruses! 🔬❄️ www.nwo.nl/nieuws/109-v... Congratulations to all the other awardees!

nwo.nl109 Vidi-aanvragen toegewezen aan talentvolle onderzoekers | NWONWO heeft maar liefst 109 wetenschappers uit de wetenschapsdomeinen Exacte en Natuurwetenschappen (ENW), Toegepaste en Technische Wetenschappen (TTW), Sociale en Geesteswetenschappen (SGW) en Zorgonde...

Luuk Loeff reposted

Luuk Loeff reposted

14 years ago, the revolutionary genetic tool CRISPR/Cas9 was published in Science, work that Emmanuelle Charpentier and Jennifer Doudna won a Nobel Prize for in 2020. On #WorldCRISPRDay, read the landmark paper that describes the discovery: https://scim.ag/4oot170

Luuk Loeff reposted

Excited to share this one, led by Theo and my postdoc Bel! We uncover how RNase E generates pAgo guide RNAs and how SPARMA turns that recognition into defense. We solved the cryo-EM structures in the Bravo lab. Great collaboration with Swarts & Zaremba! 🧬 www.researchsquare.com/article/rs-1...

researchsquare.comRNase E-dependent guide generation and activation of the SPARMA defense systemThe evolutionary arms race between prokaryotes and their invaders has driven extensive diversification of defense systems. Prokaryotic Argonautes (pAgos) comprise a diverse family of defense systems i...
Théophile Niault@tniault.bsky.social

New preprint from my Post-Doc in the Swarts lab How are the guide RNAs generated that direct prokaryotic Argonautes to invading DNA? This has been an open question for >10 years. Our new study reveals that the host housekeeping enzyme RNase E is responsible! A 🧵: 1/14

Luuk Loeff reposted

🔥Preprint alert!🔥 RNase E-dependent guide generation and activation of the SPARMA defense system Read the thread by Theo on how the short pAgo system SPARMA works, how pAgo guide RNAs are generated, and how pAgo autoimmunity is prevented. Preprint here: www.researchsquare.com/article/rs-1...

researchsquare.comRNase E-dependent guide generation and activation of the SPARMA defense systemThe evolutionary arms race between prokaryotes and their invaders has driven extensive diversification of defense systems. Prokaryotic Argonautes (pAgos) comprise a diverse family of defense systems i...
Théophile Niault@tniault.bsky.social

New preprint from my Post-Doc in the Swarts lab How are the guide RNAs generated that direct prokaryotic Argonautes to invading DNA? This has been an open question for >10 years. Our new study reveals that the host housekeeping enzyme RNase E is responsible! A 🧵: 1/14

Luuk Loeff reposted

New preprint from my Post-Doc in the Swarts lab How are the guide RNAs generated that direct prokaryotic Argonautes to invading DNA? This has been an open question for >10 years. Our new study reveals that the host housekeeping enzyme RNase E is responsible! A 🧵: 1/14

Exciting times for cryo-EM in NL 🇳🇱! As part of EMPower, two new Titan Krios G5 microscopes have been installed at NeCEN in Leiden and Utrecht. First benchmarks with ApoF reached 1.12 Å resolution 🤯. Looking forward to seeing all the exciting science these microscopes will enable! 🔬

Luuk Loeff reposted

Luuk Loeff reposted

Luuk Loeff reposted

1/13 — New pre-print from the Sternberg Lab in collaboration with Leifu Chang's Lab! TnpB nucleases have repeatedly given rise to TldRs, nuclease-dead RNA-guided transcription factors. Here we define the biological role of one TldR clade in its native host. Story: www.biorxiv.org/content/10.6...

Luuk Loeff reposted

The final version of our manuscript on TnSeq in bacteriophages (“HIDEN-SEQ”) is out today – if you have an interesting phage phenotype and want to know the underlying genetic basis, this one is for you! 1/4

Luuk Loeff reposted

Luuk Loeff reposted

🎉 Our first paper from the Querques lab is out! We uncover the molecular checkpoints controlling cut-and-paste transposition by CRISPR-associated transposons. Congrats to Mateusz & the whole team! 🧬 www.nature.com/articles/s41... @univie.ac.at @meduniwien.ac.at

nature.comTransposon end recognition and excision mechanisms of type I-F CRISPR-associated transposases - Nature CommunicationsCRISPR-associated transposons mediate RNA-guided DNA integration, but the molecular basis of transposase function remains poorly understood. Here, the authors uncover the mechanism of a highly active ...
Max Perutz Labs Vienna@maxperutzlabs.ac.at

Paper alert! 📢 The @irmaquerques.bsky.social lab, with Mateusz Walter as co-first author, reveals in @natcomms.nature.com the molecular checkpoints that control how and when CRISPR-associated transposons move DNA ➡️ tinyurl.com/4mzkhwz6 @univie.ac.at @meduniwien.ac.at

Luuk Loeff reposted

Luuk Loeff reposted

Luuk Loeff reposted

Luuk Loeff reposted

The shared principles of human and bacterial antiviral immunity An honor to highlight remarkable discoveries from many labs over the past 12 years that unite previously disparate fields of how animal cells and prokaryotes defend against viruses. www.nature.com/articles/s41... rdcu.be/fzwyB

nature.comShared principles of human and bacterial antiviral immunity - NatureThe Review describes shared ancient, conserved mechanisms between human antiviral immunity and bacterial anti-phage systems, outlining universal principles of pathogen sensing, signalling and effector...

Luuk Loeff reposted

We’re so excited to share our new paper, where we tackle the wealth of structural and functional diversity of anti-phage sensors across bacteria (1/6)

Luuk Loeff reposted

Luuk Loeff reposted

Luuk Loeff reposted

🚨 We're hiring! My new lab at EMBL Hamburg is looking for a Research Technician. I'm looking for someone excited by phages, metabolism, enzymes, structural biology and bacterial immunity—if you know the right person, please share this post!🧵⬇️ Apply here: embl.wd103.myworkdayjobs.com/en-US/EMBL/j...

embl.wd103.myworkdayjobs.comResearch Technician (Osterman Group – Metabolism-driven immunity)EMBL Hamburg / CSSB The European Molecular Biology Laboratory (EMBL) is Europe’s flagship life sciences organization, with more than 110 independent research groups across Heidelberg, Hamburg, Grenobl...

Luuk Loeff reposted

1/11 New preprint from the Sternberg lab in collaboration with the Fernández lab! We are excited to share our structure-function study of DRT10, a bacterial defense-associated reverse transcriptase that synthesizes long tandem-repeat DNA.🧵 Read the full story here: www.biorxiv.org/content/10.6...

biorxiv.orgMechanism of tandem-repeat DNA synthesis by an antiviral reverse transcriptaseDefense-associated reverse transcriptases (DRTs) employ DNA synthesis to protect bacteria against phage infection[1][1],[2][2]. We previously showed that DRT10, a tripartite system comprising an RT, a...

Luuk Loeff reposted

Our paper out in Science today: The Metis defense system senses molecular byproducts released when a phage degrades the bacterial genome, and then prevents replication of the phage in the infected cell Congratulations @ostermanilya.bsky.social and co-authors!

science.orgBacteria sense virus-induced genome degradation via methylated mononucleotidesPhages often degrade the genome of their bacterial host to individual nucleotides. Here we describe Metis, a bacterial defense system that directly senses phage-mediated host genome degradation. Metis...
Osterman Ilya@ostermanilya.bsky.social

Excited to share that our Metis story is now published in Science! 🎉 Bacteria can sense phage-induced degradation of their genome and activate immunity. Many thanks to everyone who contributed to this work. 📄 www.science.org/doi/10.1126/... More details in my earlier thread 🧵⬇️

Luuk Loeff reposted

Humans and bacteria share strategies to defend against viruses. We wondered: could they use each other's genes? Yes, both can! Bacteria can use human immune genes to defend against phages AND Human cells can use bacterial genes for viral defense. www.biorxiv.org/content/10.6...

biorxiv.orgBacterial and human exonucleases mediate interkingdom antiviral immunityAll kingdoms of life have developed strategies to limit viral infection. In humans, interferons induce a suite of antiviral factors that collectively provide immunity. Some human immune genes are homo...

Luuk Loeff reposted

Join us! Postdoc position (2-3 years) in our lab @molbiolau.bsky.social Looking for candidates with experience in cell culture, genome editing, biochemistry, and/or structural biology. Application opens in August via AU's system but informal enquiries by email are welcome from now. (1/2)

Luuk Loeff reposted

Luuk Loeff reposted

@romihadary.bsky.social and @soreklab.bsky.social 's discovery that sponge proteins constitute enormous families of viral immune evasion factors is now out in @natmicrobiol.nature.com @reneechang.bsky.social and our lab were happy to help with this story! www.nature.com/articles/s41...

nature.comFunctional diversity of phage sponge proteins that sequester host immune signals - Nature MicrobiologyA functional screen reveals phage sponge proteins that bind Pycsar, Thoeris and CBASS signalling molecules to inhibit bacterial immunity.
Kranzusch Lab@kranzuschlab.bsky.social

Two major breakthroughs for the nucleotide immune signaling field in pre-print by @romihadary.bsky.social @soreklab.bsky.social www.biorxiv.org/content/10.1... (1) Beautiful bioinformatic analyses reveal known viral nucleotide sponges are members of enormous protein families ubiquitous in phages

Luuk Loeff reposted

Our aRES story is finally out 😀 Beyond what was reported in the preprint, we found that aRES is activated by direct binding of the phage DNA polymerase. Another NAD-degrading defense system — and multiple phage strategies to overcome it. www.sciencedirect.com/science/arti...

sciencedirect.comBacterial defense via RES-mediated NAD+ depletion is countered by phage phosphatasesMany bacterial defense systems restrict phage infection by breaking down the molecule nicotinamide (Nam) adenine dinucleotide (NAD+) into adenosine di…
Osterman Ilya@ostermanilya.bsky.social

🧬 Metabolic arms race continues! We discovered a new NAD⁺-depleting bacterial immune system aRES and phage enzymes that overcome it. Our preprint is out: www.biorxiv.org/content/10.6...

biorxiv.orgBacterial defense via RES-mediated NAD+ depletion is countered by phage phosphatasesMany 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-1″-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