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Daan C. Swarts

@dcswarts.bsky.social

210 followers 76 following 36 posts

Group leader at Wageningen University & Research, NL | Prokaryotic immune systems | Views are my own

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Daan C. Swarts @dcswarts.bsky.social · Aug 28

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!

Daan C. Swarts @dcswarts.bsky.social · Aug 28

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.

Martin Pacesa @martinpacesa.bsky.social · Aug 27

Exciting to see our protein binder design pipeline BindCraft published in its final form in @Nature ! This has been an amazing collaborative effort with Lennart, Christian, @sokrypton.org, Bruno and many other amazing lab members and collaborators.

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

Daan C. Swarts @dcswarts.bsky.social · Jun 16

Congrats Jorge, fantastic!

Daan C. Swarts @dcswarts.bsky.social · May 14

Fantastic work, congrats Anna!

These filaments are so cool :)

Anna Kanevskaya @annakanevskaya.bsky.social · Apr 7

News from the world of pAgos:
We explored a distinct clade of short pAgos associated with HNH nuclease partners, which we named SPARHA, and discovered that they protect bacteria from phages and plasmids via abortive infection. Upon activation, SPARHA oligomerizes, forming filaments.
A long 🧵

Daan C. Swarts @dcswarts.bsky.social · May 13

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!

Daan C. Swarts @dcswarts.bsky.social · May 13

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 .

Daan C. Swarts @dcswarts.bsky.social · May 13

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.

Daan C. Swarts @dcswarts.bsky.social · May 13

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...

Daan C. Swarts @dcswarts.bsky.social · May 13

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.

Daan C. Swarts @dcswarts.bsky.social · May 13

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.

Daan C. Swarts @dcswarts.bsky.social · May 13

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?

Daan C. Swarts @dcswarts.bsky.social · May 13

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.

Daan C. Swarts @dcswarts.bsky.social · May 13

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.

Daan C. Swarts @dcswarts.bsky.social · May 13

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.

Daan C. Swarts @dcswarts.bsky.social · May 13

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? 🤔

Daan C. Swarts @dcswarts.bsky.social · May 13

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?

Reposted by Daan C. Swarts

Gemma C. Atkinson @gemmaatkinson.bsky.social · Mar 7

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/...

Associate Senior Lecturer (DDLS fellow) in data driven epidemiology and biology of infection

Lund is strategically positioned close to the continent, hosting major national and European research infrastructures, such as MAX.IV Laboratory and the European Spallation Source (ESS). In the field

Reposted by Daan C. Swarts

Dr Ino Agrafioti @inoagrafioti.bsky.social · Jan 23

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/...

134 researchers supported to turn their science into practice

In the final round of the 2024 European Research Council (ERC) Proof of Concept grant competition, 134 projects will receive support, bringing the total number of grants awarded under the 2024 work pr...

Daan C. Swarts @dcswarts.bsky.social · Jan 23

Excited to have been awarded an ERC Proof-of-Concept grant to further explore the possibilities to use prokaryotic Argonautes for diagnostics applications! 🥳

Daan C. Swarts @dcswarts.bsky.social · Jan 7

www.cell.com/cell-reports...

And this one...

Daan C. Swarts @dcswarts.bsky.social · Jan 7

www.sciencedirect.com/science/arti... Thanks for letting me know, this one should work!

Distribution of bacterial DNA repair proteins and their co-occurrence with immune systems

Bacteria encode various DNA repair pathways to maintain genome integrity. However, the high degree of homology between DNA repair proteins or their do…

www.sciencedirect.com

Daan C. Swarts @dcswarts.bsky.social · Jan 7

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!

Daan C. Swarts @dcswarts.bsky.social · Jan 7

We propose that beyond unraveling new anti-defence mechanisms, efforts should also aim to clarify the evolutionary and ecological drivers of anti-defence systems, which currently remain poorly explored.

Daan C. Swarts @dcswarts.bsky.social · Jan 7

Finally, we discuss ecological drivers and consequences of interactions between defence and anti-defence systems.

Daan C. Swarts @dcswarts.bsky.social · Jan 7

We review how regulation of anti-defense systems expression can be of importance, and how defence systems and their anti-defence systems have co-evolved in the arms race between bacterial hosts and their mobile genetic elements.