Our paper is out! Hiding in plain sight among Cas12a nucleases, Cas12a3 cleaves not its RNA target but the 3′ ends of tRNA. Huge thanks to all who made this possible, especially the Beisel lab, Biao & Dirk for the structure, & @sebastianglatt.bsky.social for all things tRNA. doi.org/10.1038/s415...
VERY much looking forward to cool science at the next edition of the Symposium of Immune Sytems of Bacteria in New York in 2026!
Hope to see many of you there 🥳
📢 We have multiple open PhD positions to study bacterial immune systems using cutting-edge cryo-EM, microbiology, and biochemistry in our group! Join us and uncover how bacterial defenses eliminate predators and engineer next-gen biotech tools.
🔥 Apply by Jan 8, 2026
Details: phd.pages.ista.ac.at
Great Aude! Just an update, we have our own website:
www.swartslab.org
Also I am not sure when I stop being an early career scientist 🤐
Congratulations Daniel! Fantastic :D
Congrats Fabai 👏!
Lab’s first paper is out!! We show the first structures of #Asgard #chromatin by #cryo-EM 🧬❄️
Asgard histones form closed and open hypernucleosomes. Closed are conserved across #Archaea, while open resemble eukaryotic H3–H4 octasomes and are Asgard-specific. More here: www.cell.com/molecular-ce...
One week left to apply!!
We are excited and grateful that the main authors thought that prokaryotic Argonaute proteins were a cool target to design binders for, and that we could contribute to this paper. We will continue using BindCraft to further probe our proteins of interest!
BindCraft can be used to design synthetic protein binders with incredible accuracy and success rate - Out now in Nature.
BindCraft displays perfectly how AI-based tools can be used to accelerate biological research (and clinical applications). I think this is a must-read paper.
Congrats Jorge, fantastic!
Fantastic work, congrats Anna!
These filaments are so cool :)
In addition @sumanthmutte.bsky.social , @tniault.bsky.social @patrickbarendse.bsky.social @belkoopal.bsky.social and many blueskyless co-authors. Also with further help of collaborator @hauryliuk.bsky.social!
Thanks to all who contributed to this multidisciplinary study!
The first steps of this work were taken a long time ago during my @embo.org fellowship in the Jinek lab @martinjinek.bsky.social, but the main work was carried out by the talented Pilar Bobadilla Ugarte in our group @bic-wur.bsky.social @w-u-r.bsky.social funded by @erc.europa.eu .
This suggests that in absence of repair complexes, pAgos need ACE to generate guide DNAs.
These findings corroborate the importance of RecBCD/AddAB for long-A pAgos and highlights the versatility of immune systems to adapt to distinct hosts with different accessory proteins.
hat is the relevance of ACE? Jolly et al. and Kuzmenko et al., demonstrated that DNA repair complexes AddAB/RecBCD are major drivers of guide DNA generation for long-A pAgos.
In another study, we recently showed that cyanobacteria lack RecBCD/AddAB:
sciencedirect.com/science/arti...
But what does it mean in vivo? We show that, in E. coli, while the cyanobacterial pAgo alone can provide defense against plasmids and phages, ACE can enhance the interference phenotype (at least for plasmids) demonstrating these proteins function in conjunction.
Co-expression of the cyanobacterial pAgo and ACE in E. coli reveals that pAgo-associated guide DNAs are (further) processed (shortened) by ACE. We show that longer guide DNAs are not functional, which shows that ACE contributes to guide DNA generation in coli.
The cyanobacterial pAgo and its ACE partner form a heterodimeric complex in which activity of ACE1 is modulated. But this still leaves a question: Is ACE1 important for guide generation or (further) target DNA a degradation?
Structural and biochemical characterization of ACE shows it is a DNA nuclease. Its catalytic site is buried in a channel that can only be accessed by single stranded DNA. Analysis of sequencing products show that ACE preferentially cleaves ssDNA upstream of guanine residues.
Investigation of the cyanobacterial pAgos shows that they are DNA-guided DNA cleaving pAgos, akin to various other long-A pAgos (TtAgo, CbAgo, PfAgo).
Those experiments as well as the crystal structure of CtAgo do not reveal why they would need ACE as partner.
Cyanobacterial long-A pAgos are co-encoded with Cas4 family proteins (from hereon: ACE for Argonaute associated Cas4-like enzyme).
Our analysis shows that despite their family name, ACEs look more like the nuclease domains of AdnAB and AddAB than like CRISPR-Cas4.
Various long-A pAgos act as stand-alone immune systems. They utilize small DNA guides to recognize and cleave target DNA.
Certain long-A pAgos are co-encoded with accessory proteins, which suggests these proteins function in conjunction. What is the need of these proteins? 🤔
Out now: Cyanobacterial Argonautes and Cas4 family nucleases cooperate to interfere with invading DNA
cell.com/molecular-ce...
Most long-A pAgos interfere with invading DNA solo. Why then are cyanobacterial pAgos co-encoded with a Cas4-like protein?
Bioinformatics junior group leader position in Lund, specialising in infection and/or epidemiology. These are really nice positions with generous support. Please spread the word to anyone who might be interested in becoming our colleague! lu.varbi.com/en/what:job/...
Congratulations to LS1 #ERC grantees @dcswarts.bsky.social and Geert van den Bogaart @unigroningen.bsky.social for their POC grants! 🥳 🥳 🥳 🥳 🥳#ERCPoC erc.europa.eu/news-events/...
Excited to have been awarded an ERC Proof-of-Concept grant to further explore the possibilities to use prokaryotic Argonautes for diagnostics applications! 🥳
www.cell.com/cell-reports...
And this one...
www.sciencedirect.com/science/arti... Thanks for letting me know, this one should work!
Together with @tniault.bsky.social, it was really fun to (again) work together with former colleagues and friends Edze Westra and Stineke van Houte on this review!
Hope that everyone interested enjoys the read!
