#mCpol)
LightNews LightNews
benadler.bsky.social
🧪🧪🧪10 incredible findings about Cas10-relative, mCpol:
result number 10 will surprise you!🧪🧪🧪

@erinedoherty.bsky.social and I teamed up to understand the role and function of Cas10-relative, mCpol, and its role in antiphage immunity. For more, check out Erin's thread 👇
erinedoherty.bsky.social Erin Doherty @erinedoherty.bsky.social · Mar 31
Preprint alert! ✨ In this project that I co-led with @benadler.bsky.social, we show that a miniature CRISPR-Cas10-like enzyme, mCpol, uses a novel inverse signaling mechanism to prevent the spread of viruses that attempt immune evasion by depleting host cyclic nucleotides.

Check it out:
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...
www.biorxiv.org
March 31, 2025 at 5:31 PM
benadler.bsky.social
Today in @nature.com , we highlight how a cousin of CRISPR-Cas10, mCpol, establishes an evolutionary trap in anti-phage immune systems.

Check out @erinedoherty.bsky.social and my work from @doudna-lab.bsky.social lab here:
www.nature.com/articles/s41...
A miniature CRISPR–Cas10 enzyme confers immunity by inhibitory signalling - Nature
Panoptes, an anti-phage defence system against virus-mediated immune suppression, is revealed.
www.nature.com
October 1, 2025 at 5:57 PM
benmorehouse.bsky.social
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!
March 31, 2025 at 10:05 PM
benadler.bsky.social
Thank you to everyone who helped make this story happen!

Obligatory meme to summarize:
“How I imagine phage facing CBASS and mCpol”
October 1, 2025 at 5:57 PM
erinedoherty.bsky.social
We determined that mCpol produced c-di-AMP and a crystal structure of mCpol bound to an ATP analog showed that regions homologous to regulatory features in Cas10 were replaced by highly stable structures, consistent with our observation that mCpol is a constitutively active cyclase.
March 31, 2025 at 4:29 PM
erinedoherty.bsky.social
Preprint alert! ✨ In this project that I co-led with @benadler.bsky.social, we show that a miniature CRISPR-Cas10-like enzyme, mCpol, uses a novel inverse signaling mechanism to prevent the spread of viruses that attempt immune evasion by depleting host cyclic nucleotides.

Check it out:
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...
www.biorxiv.org
March 31, 2025 at 4:27 PM
erinedoherty.bsky.social
Oligonucleotide synthesis upon viral infection is a cross-kingdom mechanism of immunity used to trigger an antiviral response. mCpol co-occurs with proteins from signaling systems and shares homology with oligonucleotide cyclases--

This suggested that mCpol might contribute to bacterial immunity.
Comparison of representative CBASS (top), MISS (middle) and Type III-A CRISPR-Cas loci (bottom) shows shared protein domains between CBASS and MISS (2TMβ and Cap15, 23% sequence identity) and between MISS and Type III CRISPR loci (mCpol and Cas10, 19% sequence identity). Shared protein domains are highlighted.
March 31, 2025 at 4:28 PM
erinedoherty.bsky.social
How could a constitutively active cyclase mediate an immune response specific to phage infection? We used cell-based assays, biochemistry, and fluorescence microscopy to show that loss of c-di-AMP synthesis by mCpol triggers 2TMβ oligomerization and cell death due to inner membrane collapse.
Fluorescence microscopy images showing a membrane stain, DNA stain, and merge image for conditions with or without mCpol or 2TMβ expression. Membrane lesions occur when 2TMβ is expressed in the absence of mCpol.
March 31, 2025 at 4:30 PM
danihere.bsky.social
#NC #MCpol Virginia Foxx is embarrassing herself again. 🤦🏻‍♀️ Oh and us!
andreablackmagic.bsky.social andreablackmagic.bsky.social @andreablackmagic.bsky.social · Sep 8
So this old 🦇 pearl clutching over Maxwell Frost’s remarks about school shootings is protecting pedophiles.
“Pro-life” means allowing our girls to be 🍇 by grown men.
September 9, 2025 at 4:41 AM
erinedoherty.bsky.social
We found that a locus encoding mCpol and a putative cell death effector protein 2TMβ, referred to as mCpol inverse signaling system (MISS), provided defense against a narrow range of bacteriophage by an abortive infection mechanism.
Change in efficiency of plaquing when phages of 12 unique phage genera were challenged against E. coli with ECOR31-derived MISS loci normalized to a vector control shows that MISS is a narrow spectrum anti-phage defense system
March 31, 2025 at 4:28 PM
benadler.bsky.social
Shout out to @aesully98.bsky.social @aaronwhiteley.bsky.social and @benmorehouse.bsky.social on their (excellent) complementary mCpol study!
bsky.app/profile/aesu...
March 31, 2025 at 11:31 PM
robertscotthorton.bsky.social
Cell-based experiments demonstrated that the absence or loss of mCpol-produced cyclic oligonucleotides triggers cell death, preventing the spread of viruses that attempt immune evasion by depleting host cyclic nucleotides. www.nature.com/articles/s41...
A miniature CRISPR–Cas10 enzyme confers immunity by inhibitory signalling - Nature
Panoptes, an anti-phage defence system against virus-mediated immune suppression, is revealed.
www.nature.com
October 2, 2025 at 1:37 PM
plosbiology.org
#Phages can evade #bacterial #immunity by disrupting #antiviral signals like cA3, triggering the Panoptes defense systems. @mfwhite2.bsky.social &co show that Type II Panoptes detects cA3 loss and activates a CARF-TM effector to disrupt membranes & stop infection @plosbiology.org 🧪 buff.ly/1ixwg9v
Left: Organisation and mechanism of the Panoptes System. In type I Panoptes systems, mCpol is constitutively active, generating signalling molecules that inactivate the cognate effector, 2TMβ. When an infecting phage expresses a sponge protein, the cyclic oligonucleotide pool is depleted. The Panoptes effector oligomerises, leading to membrane disruption and growth arrest or cell death. Right: CARF-TM model structure and cA3 binding. Alphafold3 model of CARF-TM in complex with cA3, including POPG molecules to simulate the membrane bilayer. The position mutated to generate the truncated CARF protein is shown by black arrows.
September 16, 2026 at 4:40 PM
plosbiology.org
#Phages can evade #bacterial #immunity by disrupting #antiviral signals like cA3, triggering Panoptes defense systems. @mfwhite2.bsky.social &co show that Type II Panoptes detects cA3 loss and activates a CARF-TM effector to disrupt membranes & stop infection @plosbiology.org 🧪 buff.ly/1ixwg9v
Left: Organisation and mechanism of the Panoptes System. In type I Panoptes systems, mCpol is constitutively active, generating signalling molecules that inactivate the cognate effector, 2TMβ. When an infecting phage expresses a sponge protein, the cyclic oligonucleotide pool is depleted. The Panoptes effector oligomerises, leading to membrane disruption and growth arrest or cell death. Right: CARF-TM model structure and cA3 binding. Alphafold3 model of CARF-TM in complex with cA3, including POPG molecules to simulate the membrane bilayer. The position mutated to generate the truncated CARF protein is shown by black arrows.
September 18, 2026 at 12:55 PM
plosbiology.org
Most #bacterial #immune systems raise an alarm when they sense a #phage. This Primer explores a @plosbiology.org study showing how type II Panoptes reverses this logic by maintaining a quiet signal & sensing infection through its sudden disappearance 🧪 Paper: buff.ly/1ixwg9v Primer: buff.ly/WmnHZBp
Type II Panoptes inverts the logic of nucleotide signaling in bacterial immunity. Top: In type III CRISPR-Cas, Cas10 synthesizes cyclic oligoadenylates (cAn) only upon infection; the signal binds and activates a CARF effector, arresting growth. Type II Panoptes does the reverse. Its mCpol enzyme produces cA3 constitutively at low levels, and this signal keeps the CARF-TM effector repressed. Infection is sensed not as the appearance of a signal, but as its disappearance: when phage enzymes (Acb1 given as an example) deplete cA3, the effector is released and growth arrests. Bottom: Because Acb1 evolved to disable cyclic-nucleotide defenses such as type III CRISPR, a phage carrying it strips cA3 as collateral damage and triggers Panoptes. A phage lacking Acb1 avoids this trap but remains vulnerable to CRISPR. Together, the two systems could impose an evolutionary trade-off on the phage.
September 17, 2026 at 8:05 AM
jnoms.bsky.social
A HUGE congrats to @erinedoherty.bsky.social, @benadler.bsky.social, and team!! What an amazing story. How can bacteria sense when phage are using pesky phosphodiesterases and sponges to interfere with cGAS-like enzymes in bacterial immunity? Enter mCpol!
erinedoherty.bsky.social Erin Doherty @erinedoherty.bsky.social · Mar 31
Preprint alert! ✨ In this project that I co-led with @benadler.bsky.social, we show that a miniature CRISPR-Cas10-like enzyme, mCpol, uses a novel inverse signaling mechanism to prevent the spread of viruses that attempt immune evasion by depleting host cyclic nucleotides.

Check it out:
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...
www.biorxiv.org
March 31, 2025 at 5:00 PM
medchemexpress.bsky.social
🚀 From Bench to Paper | #Nature: Doudna lab discovers a minimal #Cas10 #enzyme (#mCpol) that defends bacteria via c-di-AMP-based inhibitory signalling.
🚨 When #c-di-AMP drops, cells self-destruct to block phage.
Research tool: c-di-AMP (MedChemExpress, HY-12326A)
#CRISPR #BacterialImmunity
October 9, 2025 at 3:01 PM
plosbiology.org
Most #bacterial immune systems raise an alarm when they sense a #phage. This Primer explores a @plosbiology.org study showing how type II Panoptes reverses this logic by maintaining a quiet signal & sensing infection through its sudden disappearance 🧪 Paper: buff.ly/1ixwg9v Primer: buff.ly/WmnHZBp
Type II Panoptes inverts the logic of nucleotide signaling in bacterial immunity. Top: In type III CRISPR-Cas, Cas10 synthesizes cyclic oligoadenylates (cAn) only upon infection; the signal binds and activates a CARF effector, arresting growth. Type II Panoptes does the reverse. Its mCpol enzyme produces cA3 constitutively at low levels, and this signal keeps the CARF-TM effector repressed. Infection is sensed not as the appearance of a signal, but as its disappearance: when phage enzymes (Acb1 given as an example) deplete cA3, the effector is released and growth arrests. Bottom: Because Acb1 evolved to disable cyclic-nucleotide defenses such as type III CRISPR, a phage carrying it strips cA3 as collateral damage and triggers Panoptes. A phage lacking Acb1 avoids this trap but remains vulnerable to CRISPR. Together, the two systems could impose an evolutionary trade-off on the phage.
September 17, 2026 at 4:25 PM
plosbiology.org
Most #bacterial #immune systems raise an alarm when they sense a #phage. This Primer explores a @plosbiology.org study showing how type II Panoptes reverses this logic by maintaining a quiet signal & sensing infection through its sudden disappearance 🧪 Paper: buff.ly/1ixwg9v Primer: buff.ly/WmnHZBp
Type II Panoptes inverts the logic of nucleotide signaling in bacterial immunity. Top: In type III CRISPR-Cas, Cas10 synthesizes cyclic oligoadenylates (cAn) only upon infection; the signal binds and activates a CARF effector, arresting growth. Type II Panoptes does the reverse. Its mCpol enzyme produces cA3 constitutively at low levels, and this signal keeps the CARF-TM effector repressed. Infection is sensed not as the appearance of a signal, but as its disappearance: when phage enzymes (Acb1 given as an example) deplete cA3, the effector is released and growth arrests. Bottom: Because Acb1 evolved to disable cyclic-nucleotide defenses such as type III CRISPR, a phage carrying it strips cA3 as collateral damage and triggers Panoptes. A phage lacking Acb1 avoids this trap but remains vulnerable to CRISPR. Together, the two systems could impose an evolutionary trade-off on the phage.
September 18, 2026 at 1:01 PM
scienmag.bsky.social
Miniature CRISPR–Cas10 Grants Immunity via Inhibition

In a groundbreaking advance in microbial immunology, researchers have uncovered a sophisticated bacterial defense mechanism encoded at the Panoptes locus, revealing a CRISPR–Cas10-related system that subverts bacteriophage strategies by…
Miniature CRISPR–Cas10 Grants Immunity via Inhibition
In a groundbreaking advance in microbial immunology, researchers have uncovered a sophisticated bacterial defense mechanism encoded at the Panoptes locus, revealing a CRISPR–Cas10-related system that subverts bacteriophage strategies by harnessing inhibitory signaling. This miniature Cas10-like oligonucleotide cyclase, termed mCpol, operates in concert with a CBASS-like effector protein known as 2TMβ to provide immunity against viral infection through a novel biochemical pathway.
scienmag.com
October 2, 2025 at 5:14 AM
plosbiology.org
#Phages can evade #bacterial #immunity by disrupting #antiviral signals like cA3, triggering Panoptes defense systems. @mfwhite2.bsky.social &co show that Type II Panoptes detects cA3 loss and activates a CARF-TM effector to disrupt membranes & stop infection @plosbiology.org 🧪 buff.ly/1ixwg9v
Left: Organisation and mechanism of the Panoptes System. In type I Panoptes systems, mCpol is constitutively active, generating signalling molecules that inactivate the cognate effector, 2TMβ. When an infecting phage expresses a sponge protein, the cyclic oligonucleotide pool is depleted. The Panoptes effector oligomerises, leading to membrane disruption and growth arrest or cell death. Right: CARF-TM model structure and cA3 binding. Alphafold3 model of CARF-TM in complex with cA3, including POPG molecules to simulate the membrane bilayer. The position mutated to generate the truncated CARF protein is shown by black arrows.
September 17, 2026 at 8:00 AM
portaldecadiz.bsky.social
👮📚 La XI edición de MCPOL convierte a El Bosque en punto de encuentro para la formación policial

🔗 https://www.portaldecadiz.com/mas-de-cadiz/deportes/165505-la-xi-edicion-de-mcpol-convierte-a-el-bosque-en-punto-de-encuentro-para-la-formacion-policial
July 21, 2026 at 2:20 AM
thedailypub.bsky.social
Imagine a natural defense system in cells where an enzyme called mCpol constantly makes certain molecules to keep a toxic protein in check. Without these molecules, cells can self-destruct when a virus attacks, stopping the virus from spreading. This process is like a self-destruct button that pr...
A miniature CRISPR-Cas10 enzyme confers immunity by inhibitory signalling.
Published in Nature
doi.org
October 2, 2025 at 7:00 AM
thejeffdad.bsky.social
I'm not updating my personal lexicon for Tiny Hands McPol Pot. I'm still calling it the Gulf of Mexico, and the name of that mountain is Denali.
January 26, 2025 at 1:15 AM