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Ashley Sullivan

@aesully98.bsky.social
87 followers 82 following 19 posts

🦬 // PhD candidate in the Aaron Whiteley Lab at CU Boulder. she/her

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Reposted by Ashley Sullivan
bioRxiv Microbiology @biorxiv-microbiol.bsky.social · 12/08/2026
Minimal diadenylate cyclases have been co-opted to detect phage immune evasion www.biorxiv.org/content/10.64898/20…
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Reposted by Ashley Sullivan
Ady Ragucci @aragucci.bsky.social · 12/08/2026
Excited to share our story on diadenylate cyclases in bacterial immunity! Building on the discovery of Panoptes, we present Panoptoo: a DAC operon that uses cUA to guard against phage infection. Grateful to @daniellehaley.bsky.social and @kranzuschlab.bsky.social www.biorxiv.org/content/10.6...
biorxiv.org
Bacterial diadenylate cyclase domains synthesize diverse nucleotide signals in anti-phage defense
Bacterial diadenylate cyclase (DAC) enzymes synthesize the nucleotide signal 3′3′ cyclic di-AMP (3′3′-c-di-AMP) to control osmoregulation, cell-wall homeostasis, and DNA-damage responses. Here we disc...
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Reposted by Ashley Sullivan
Ben Morehouse @benmorehouse.bsky.social · 12/08/2026
I hope you can appreciate that PanDA really is Panoptes-like in its mechanism. Panoptoo if you will! -> see the excellent complementary study that also just launched from our friends @aragucci.bsky.social and Danielle Haley in the @kranzuschlab.bsky.social !!! www.biorxiv.org/content/10.6...
biorxiv.org
Bacterial diadenylate cyclase domains synthesize diverse nucleotide signals in anti-phage defense
Bacterial diadenylate cyclase (DAC) enzymes synthesize the nucleotide signal 3′3′ cyclic di-AMP (3′3′-c-di-AMP) to control osmoregulation, cell-wall homeostasis, and DNA-damage responses. Here we disc...
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Reposted by Ashley Sullivan
Ben Morehouse @benmorehouse.bsky.social · 12/08/2026
Today we are excited to introduce you to PanDA 🐼🐼🐼, a newly uncovered antiphage system!! Attendees at @SISB2026 would have heard a little about this from graduate student Ali Nabhani back in May, but we are now out here in preprint form and delighted to share more of the details. (Thread below)
biorxiv.org
Minimal diadenylate cyclases have been co-opted to detect phage immune evasion
Many bacterial immune defenses transmit recognition of phage infection via the generation of diverse cyclic nucleotide second messengers. Phage have evolved to subvert this kind of immunity by sequest...
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Reposted by Ashley Sullivan
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026
I’m thrilled to share an update to our work on bacterial NACHT domain containing proteins! In our last preprint, we reported that bNACHT11 is activated by multiple phage proteins. We’ve now expanded this work with structural insight and investigation of programmed cell death following activation.
biorxiv.org
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Ashley Sullivan @aesully98.bsky.social · 03/10/2025
Finally, thank you to @mfwhite2.bsky.social for the wonderful summary of these stories! www.nature.com/articles/d41...
nature.com
Bacteria use a decoy defence molecule to set a trap for viruses
Some bacterial-infecting viruses use ‘sponges’ to mop up defence molecules, but bacteria can fight back by responding when a sponge captures decoy molecules.
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Ashley Sullivan @aesully98.bsky.social · 03/10/2025
Congrats as well to @erinedoherty.bsky.social and @benadler.bsky.social et al. in the @doudna-lab.bsky.social lab for their excellent complementary work on Panoptes! www.nature.com/articles/s41...
nature.com
A miniature CRISPR–Cas10 enzyme confers immunity by inhibitory signalling - Nature
Panoptes, an anti-phage defence system against virus-mediated immune suppression, is revealed.
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Ashley Sullivan @aesully98.bsky.social · 03/10/2025
Huge shoutout and thanks to my lab mates in the @aaronwhiteley.bsky.social lab and our collaborators in the @benmorehouse.bsky.social lab. This work would not have been possible without you all! 🫶🏻
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Ashley Sullivan @aesully98.bsky.social · 03/10/2025
A little late to the Panoptes party, but I’m delighted to share that our paper is published! 👁️ www.nature.com/articles/s41...
nature.com
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.
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Malcolm White @mfwhite2.bsky.social · 02/10/2025
My pleasure @erinedoherty.bsky.social and @benmorehouse.bsky.social - for me this was the stand-out discovery of the last year in the field
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Erin Doherty @erinedoherty.bsky.social · 02/10/2025
Very excited to see our work appear alongside findings from @aaronwhiteley.bsky.social & @benmorehouse.bsky.social ! www.nature.com/articles/s41...
nature.com
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.
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Reposted by Ashley Sullivan
Erin Doherty @erinedoherty.bsky.social · 02/10/2025
Now online at @nature.com we show how the Panoptes defense system protects against viruses that attempt immune evasion - and expands our understanding of the role of oligonucleotides in immunity. Check out this work co-led with @benadler.bsky.social here: www.nature.com/articles/s41...
nature.com
A miniature CRISPR–Cas10 enzyme confers immunity by inhibitory signalling - Nature
Panoptes, an anti-phage defence system against virus-mediated immune suppression, is revealed.
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Reposted by Ashley Sullivan
Ben Adler @benadler.bsky.social · 01/10/2025
Thank you to everyone who helped make this story happen! Obligatory meme to summarize: “How I imagine phage facing CBASS and mCpol”
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Reposted by Ashley Sullivan
Ben Adler @benadler.bsky.social · 01/10/2025
Our sister-story from our friends @aesully98.bsky.social , @benmorehouse.bsky.social and @aaronwhiteley.bsky.social is out today as well! Congratulations!! www.nature.com/articles/s41...
nature.com
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.
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Reposted by Ashley Sullivan
Kranzusch Lab @kranzuschlab.bsky.social · 17/07/2025
A new preprint led by Sonomi Yamaguchi in our lab describes a bacterial anti-phage defense system named Clover that uses nucleotide signals to both activate and inhibit host immunity. www.biorxiv.org/content/10.1...
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Reposted by Ashley Sullivan
Sorek Lab @soreklab.bsky.social · 14/07/2025
Preprint: “Structural modeling reveals viral proteins that manipulate host immune signaling” Using AI-guided structural modeling, we find new families of viral proteins that sequester or cleave host immune signaling molecules Congrats Nitzan Tal! www.biorxiv.org/content/10.1...
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toninagy3.bsky.social @toninagy3.bsky.social · 11/07/2025
I am delighted to share that my work in the @aaronwhiteley.bsky.social lab is now on bioRxiv! We used a large-scale genetic screen to begin defining the vast landscape of phage proteins that trigger immune signaling in bacteria. www.biorxiv.org/content/10.1...
biorxiv.org
Identifying phage proteins that activate the bacterial innate immune system
Bacteria have evolved sophisticated antiphage systems that halt phage replication upon detecting specific phage triggers. Identifying phage triggers is crucial to our understanding of immune signaling...
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Reposted by Ashley Sullivan
Amy Conte @amyconte.bsky.social · 04/06/2025
Excited to share that my work in the @aaronwhiteley.bsky.social lab describing chaperone-mediated phage sensing by a bacterial NLR-related protein is out in @plosbiology.org!
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Reposted by Ashley Sullivan
Ben Morehouse @benmorehouse.bsky.social · 31/03/2025
CBASS, CRISPR, and mCpol- oh my! What a satisfying collaboration with @aaronwhiteley.bsky.social 's lab- we uncovered a new cyclic dinucleotide signaling pathway, but it doesn't work how you'd expect! Check out the thread from @aesully98.bsky.social for an overview of the most important findings!
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
Also—check out the complementary work led by @erinedoherty.bsky.social and @benadler.bsky.social in @doudna-lab.bsky.social lab that just went up on bioRxiv!
biorxiv.org
A miniature CRISPR-Cas10 enzyme confers immunity by an inverse signaling pathway
Microbial and viral co-evolution has created immunity mechanisms involving oligonucleotide signaling that share mechanistic features with human anti-viral systems. In these pathways, including CBASS a...
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
Huge shout-out to all of the authors from the @aaronwhiteley.bsky.social and @benmorehouse.bsky.social labs that were so instrumental to this project! A special thank you to our collaborators L. Aravind and Max Burroughs for their incredible bioinformatic analyses!
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
In total, we uncovered a novel mechanism of immune evasion sensing in bacteria. The Panoptes system is part of a “layered” immune system that flips the liability of a nucleotide-derived second messenger in immune signaling against the phage, adding an interesting dimension to phage-bacteria warfare.
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
Finally, we wanted to explore the relationship between CBASS and Panoptes, given the importance of Acb2 in both nucleotide-based signaling systems. We found that 53% of all Panoptes systems co-occur with CBASS, suggesting that Panoptes systems are predominantly guardians of CBASS in bacteria.
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
Consistent with this, we found that OptE robustly inhibited bacterial growth unless an OptS-derived nucleotide was present and that OptS constitutively synthesizes 2′,3′-c-di-AMP in vivo in the absence of phage infection.
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
These data led us to hypothesize that OptS-synthesized nucleotides were actually inhibiting, rather than activating, the OptE effector. Upon phage infection, however, Acb2 sequesters the OptS product away from OptE, unleashing its growth inhibition effect.
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
These findings left us puzzled: How does the Acb2 nucleotide sponge protein activate the Panoptes system? Based on its ability to bind diverse nucleotide products, we proposed that Acb2 also binds the product of OptS (2′,3′-c-di-AMP), which is exactly what we found.
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
Acb2 was recently discovered by the Bondy-Denomy and Chen Labs to be an anti-defense protein that acts as a nucleotide “sponge,” sequestering CBASS-derived cyclic oligonucleotide signaling molecules.
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
Intriguingly, the escaper phages we identified encoded loss-of-function mutations exclusively in the anti-CBASS 2 (acb2) gene. Consistent with this, we found that acb2 was necessary and sufficient to activate Panoptes defense.
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
We now knew that nucleotide signaling was a key component of the Panoptes system, but we were left wondering: how does the phage activate defense? To answer this question, we turned to phages that were able to escape Panoptes.
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
We tested the activity of OptS by incubating it with a range of NTPs and found that it used ATP as a substrate to specifically produce 2′,3′-c-di-AMP, an isomer of c-di-AMP. We used a series of phosphodiesterases to show that the linkage included a 3′–5′ and 2′–5′ bond.
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
To better understand the mechanism of this system, we determined a crystal structure of OptS and found that it resembled the catalytic regions of both Cas10 and GGDEF enzymes and formed a stable tetrameric complex.
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
We first explored the antiphage activity of Panoptes and found that it robustly and specifically defended against Teven phages from the Straboviridae family.
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
Nucleotide-based signaling is a hallmark of many antiphage systems (CBASS, Pycsar, Thoeris, etc.). Here we investigated Panoptes, a two-gene operon (optSE) that we predicted would similarly use nucleotide second messengers to carry out an immune response.
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Ashley Sullivan @aesully98.bsky.social · 31/03/2025
Excited to share that my work from the @aaronwhiteley.bsky.social lab is now on bioRxiv! With @benmorehouse.bsky.social, we discovered that the Panoptes defense system—named after the all-seeing watchman of Hera—uses decoy nucleotides to detect phage anti-defense proteins.
biorxiv.org
A minimal CRISPR polymerase produces decoy cyclic nucleotides to detect phage anti-defense proteins
Bacteria use antiphage systems to combat phages, their ubiquitous competitors, and evolve new defenses through repeated reshuffling of basic functional units into novel reformulations. A common theme ...
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Reposted by Ashley Sullivan
Miriam Goldstein @miriamgoldstein.bsky.social · 06/02/2025
Just in case you thought that removing DEI criteria would mean that everyone is competing equally: NIH is removing grad students from underrepresented backgrounds from the applicant pool altogether. Their applications will not be considered. Other students, not from these backgrounds, will be.
Update: They were removed from our reviewer assignments completely. I'm so sorry to all those graduate students. 

Anonymous to protect the identity of the NIH employee I spoke to...I am on study section next month to discuss F awards. We were just instructed to put the F31-Diversity applications on the bottom of our priority list for review because there is a chance we may not be able to review them. My heart is breaking for the grad students and their mentors that put so much work into these just for them to be disqualified and thrown out.
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Emily Kibby @emilykibby.bsky.social · 18/12/2024
I’m so excited to share that some of my grad work in the @aaronwhiteley lab is now available on bioRxiv! We used an AlphaFold-multimer screen to uncover how a bacterial NLR-related proteins senses multiple phage-encoded proteins to confer phage protection. Link: www.biorxiv.org/content/10.1...
biorxiv.org
A bacterial NLR-related protein recognizes multiple unrelated phage triggers to sense infection
Immune systems must rapidly sense viral infections to initiate antiviral signaling and protect the host. Bacteria encode >100 distinct viral (phage) defense systems and each has evolved to sense cruci...
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Reposted by Ashley Sullivan
Aaron Whiteley @aaronwhiteley.bsky.social · 01/03/2024
Our review comparing bacterial and eukaryotic immune systems is out now. Check out Hannah’s thread for the highlights! www.nature.com/articles/s41...
nature.com
Conservation and similarity of bacterial and eukaryotic innate immunity - Nature Reviews Microbiology
In this Review, Ledvina and Whiteley highlight the key similarities between eukaryotic and bacterial innate immune systems, exploring conserved immune components and signalling strategies, as well as ...
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