Erin Doherty
@erinedoherty.bsky.social
Postdoc @ Doudna Lab, UC Berkeley 🧬 | Chemical & Structural Biology | Immunity Mechanisms | CRISPR | RNA-Editing |
F32 NRSA | Berkeley Chancellor's Fellow
UC Davis Beal Lab Alum | Former CIRM, NIH F31 & NIH T32
F32 NRSA | Berkeley Chancellor's Fellow
UC Davis Beal Lab Alum | Former CIRM, NIH F31 & NIH T32
Such a privilege to see my summer mentee present her work at #ABRCMS2025!
November 23, 2025 at 2:21 AM
Such a privilege to see my summer mentee present her work at #ABRCMS2025!
So grateful for the collective action that reversed this decision - the PPFP will continue!
November 23, 2025 at 2:14 AM
So grateful for the collective action that reversed this decision - the PPFP will continue!
Immune activation upon cyclic oligonucleotide depletion prevents the spread of viruses that attempt immune evasion by depleting host cyclic nucleotides.
October 2, 2025 at 3:05 AM
Immune activation upon cyclic oligonucleotide depletion prevents the spread of viruses that attempt immune evasion by depleting host cyclic nucleotides.
Our findings suggest that PDE substrate specificity reflects a dynamic evolutionary arms race, with both viruses & hosts continually redefining the signaling landscape. Recurrent 2H PDE adaptation likely enables viruses to counter molecules responsible for a variety of bacterial immune defenses.
August 22, 2025 at 7:29 PM
Our findings suggest that PDE substrate specificity reflects a dynamic evolutionary arms race, with both viruses & hosts continually redefining the signaling landscape. Recurrent 2H PDE adaptation likely enables viruses to counter molecules responsible for a variety of bacterial immune defenses.
While more promiscuous PDEs like T4 Acb1 activate Panoptes, PDE-9 avoided Panoptes activation. The combined ability of PDE-9 to degrade CBASS messengers and avoid Panoptes repressor molecules demonstrates the ability of phage to evade multiple immune systems via a single antidefense protein.
August 22, 2025 at 7:23 PM
While more promiscuous PDEs like T4 Acb1 activate Panoptes, PDE-9 avoided Panoptes activation. The combined ability of PDE-9 to degrade CBASS messengers and avoid Panoptes repressor molecules demonstrates the ability of phage to evade multiple immune systems via a single antidefense protein.
We, along with the @benmorehouse.bsky.social and @aaronwhiteley.bsky.social groups recently described Panoptes: A bacterial immune system where 2’3’-c-di-AMP represses a toxic effector. Viral enzymes like Acb1 degrade this messenger, activating Panoptes.
August 22, 2025 at 7:20 PM
We, along with the @benmorehouse.bsky.social and @aaronwhiteley.bsky.social groups recently described Panoptes: A bacterial immune system where 2’3’-c-di-AMP represses a toxic effector. Viral enzymes like Acb1 degrade this messenger, activating Panoptes.
We created a chimera of the PDE-9 core and the lid from a related PDE and found that it retained the substrate preferences of PDE-9, suggesting that the enzyme core is responsible for substrate specificity rather than the structurally variable lid region.
August 22, 2025 at 7:19 PM
We created a chimera of the PDE-9 core and the lid from a related PDE and found that it retained the substrate preferences of PDE-9, suggesting that the enzyme core is responsible for substrate specificity rather than the structurally variable lid region.
PDEs use divergent 'lids' to enable activity, predicted to control substrate adaptation. To probe this specificity, we solved 2 PDE-9 structures (open/closed lid). Unexpectedly, the PDE-9 lid extends from the opposite terminus of related PDEs and adopts a distinct closed conformation
August 22, 2025 at 7:18 PM
PDEs use divergent 'lids' to enable activity, predicted to control substrate adaptation. To probe this specificity, we solved 2 PDE-9 structures (open/closed lid). Unexpectedly, the PDE-9 lid extends from the opposite terminus of related PDEs and adopts a distinct closed conformation
We found that the structural group with the broadest substrate scope contained PDEs with notable differences in targeting. In particular, 2H PDE-9 robustly degrades 3’3’-cGAMP, a common CBASS immune messenger, but shows minimal activity against other messengers including 2’3’-cdiAMP.
August 22, 2025 at 7:16 PM
We found that the structural group with the broadest substrate scope contained PDEs with notable differences in targeting. In particular, 2H PDE-9 robustly degrades 3’3’-cGAMP, a common CBASS immune messenger, but shows minimal activity against other messengers including 2’3’-cdiAMP.
To determine the breadth of targeting by viral 2H PDEs, we purified 16 candidates & carried out assays vs oligonucleotide-based messengers from different signaling systems. Strikingly, the different viral 2H PDEs displayed unique substrate scope and preferences that correlated with structural groups
August 22, 2025 at 7:14 PM
To determine the breadth of targeting by viral 2H PDEs, we purified 16 candidates & carried out assays vs oligonucleotide-based messengers from different signaling systems. Strikingly, the different viral 2H PDEs displayed unique substrate scope and preferences that correlated with structural groups
All-by-all structural alignments with DALI revealed that the 2H PDEs are structurally heterogeneous and fall within distinct structural groups. We reasoned that this structural variation may enable diversification of biochemical activity and cleavage of diverse nucleotide substrates.
August 22, 2025 at 7:12 PM
All-by-all structural alignments with DALI revealed that the 2H PDEs are structurally heterogeneous and fall within distinct structural groups. We reasoned that this structural variation may enable diversification of biochemical activity and cleavage of diverse nucleotide substrates.
We used DALI to align structures of 8 known viral 2H PDEs with predicted structures of phage proteins. This led to 84 alignments, many with less than 20% sequence identity but strong structural similarity to viral 2Hs. This revealed substantial numbers of previously unidentified phage 2H PDEs.
August 22, 2025 at 7:09 PM
We used DALI to align structures of 8 known viral 2H PDEs with predicted structures of phage proteins. This led to 84 alignments, many with less than 20% sequence identity but strong structural similarity to viral 2Hs. This revealed substantial numbers of previously unidentified phage 2H PDEs.
cGAS/DncV-like nucleotidyltransferases (CD-NTases) produce nucleotide messengers to stimulate antiviral responses. We previously found that 2H PDEs used by animal and bacterial viruses degrade these messengers, suggesting that other viruses may encode 2H PDEs involved in evasion of CD-NTase immunity
August 22, 2025 at 7:07 PM
cGAS/DncV-like nucleotidyltransferases (CD-NTases) produce nucleotide messengers to stimulate antiviral responses. We previously found that 2H PDEs used by animal and bacterial viruses degrade these messengers, suggesting that other viruses may encode 2H PDEs involved in evasion of CD-NTase immunity
First major talk of my postdoc at the Immune System of Bacteria conference in Paris, sharing work from our recent preprint! Thanks #SISB2025 for fascinating themes of nucleic acids & nucleosides, inverse regulation, prophages, and more— what an exiting time to be part of this community.
April 11, 2025 at 1:42 PM
First major talk of my postdoc at the Immune System of Bacteria conference in Paris, sharing work from our recent preprint! Thanks #SISB2025 for fascinating themes of nucleic acids & nucleosides, inverse regulation, prophages, and more— what an exiting time to be part of this community.
MISS counters anti-defense proteins that disrupt cyclic oligonucleotides, safeguarding immune signaling. It's the first immune system to use toxin-antitoxin regulation, where the signaling molecule protects cell health by suppressing its effector--a novel defense against viral immune suppression!
March 31, 2025 at 4:31 PM
MISS counters anti-defense proteins that disrupt cyclic oligonucleotides, safeguarding immune signaling. It's the first immune system to use toxin-antitoxin regulation, where the signaling molecule protects cell health by suppressing its effector--a novel defense against viral immune suppression!
The inverse signaling logic suggested that disruption of immune signaling could trigger 2TMβ-induced cell death. Using cell-based assays we found that phage-encoded proteins that attempt immune evasion by depleting host cyclic oligonucleotides were both necessary and sufficient to activate MISS.
March 31, 2025 at 4:30 PM
The inverse signaling logic suggested that disruption of immune signaling could trigger 2TMβ-induced cell death. Using cell-based assays we found that phage-encoded proteins that attempt immune evasion by depleting host cyclic oligonucleotides were both necessary and sufficient to activate MISS.
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.
March 31, 2025 at 4:30 PM
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.
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
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.
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.
March 31, 2025 at 4:28 PM
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.
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.
This suggested that mCpol might contribute to bacterial immunity.
March 31, 2025 at 4:28 PM
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.
This suggested that mCpol might contribute to bacterial immunity.