Fletcher Lab
@fletcherlab.bsky.social
We investigate interesting E3 mechanisms at the frontline between virus and cell, with some virology thrown in for good measure. Ub-er fun!
At the MRC-University of Glasgow Centre for Virus Research.
https://thefletcherlab.co.uk
At the MRC-University of Glasgow Centre for Virus Research.
https://thefletcherlab.co.uk
Join @uofglasgow.bsky.social for a funded 3.5 year PhD programme:
www.gla.ac.uk/colleges/mvl...
Also up for grabs is a project on antiviral PROTACs, supervised by us and the France lab (School of Chemistry) should ubiquitin and viruses appeal! Please get in touch with any questions.
www.gla.ac.uk/colleges/mvl...
Also up for grabs is a project on antiviral PROTACs, supervised by us and the France lab (School of Chemistry) should ubiquitin and viruses appeal! Please get in touch with any questions.
www.gla.ac.uk
November 24, 2025 at 3:47 PM
Join @uofglasgow.bsky.social for a funded 3.5 year PhD programme:
www.gla.ac.uk/colleges/mvl...
Also up for grabs is a project on antiviral PROTACs, supervised by us and the France lab (School of Chemistry) should ubiquitin and viruses appeal! Please get in touch with any questions.
www.gla.ac.uk/colleges/mvl...
Also up for grabs is a project on antiviral PROTACs, supervised by us and the France lab (School of Chemistry) should ubiquitin and viruses appeal! Please get in touch with any questions.
Reposted by Fletcher Lab
Excited to share the peer-reviewed version of our work, now online in @embojournal.org! Big thanks to our reviewers and @hvodermaier.bsky.social for facilitating this process. Looking forward to continuing this fun collaboration with @michaelnadbio.bsky.social!
www.embopress.org/doi/full/10....
www.embopress.org/doi/full/10....
October 30, 2025 at 3:33 PM
Excited to share the peer-reviewed version of our work, now online in @embojournal.org! Big thanks to our reviewers and @hvodermaier.bsky.social for facilitating this process. Looking forward to continuing this fun collaboration with @michaelnadbio.bsky.social!
www.embopress.org/doi/full/10....
www.embopress.org/doi/full/10....
Reposted by Fletcher Lab
A #postdoc position in atypical #ubiquitin signalling and protein binder engineering is opening soon in my lab at DTU Bioengineering! Get in touch if you are interested.
October 30, 2025 at 2:13 PM
A #postdoc position in atypical #ubiquitin signalling and protein binder engineering is opening soon in my lab at DTU Bioengineering! Get in touch if you are interested.
🎉 Fletcher lab PhD student Emma Davies reflecting on her prize winning talk - we’re super proud of you Emma - many congrats! 🎉
@cvrinfo.bsky.social @uofgsii.bsky.social @uofgmvls.bsky.social
@cvrinfo.bsky.social @uofgsii.bsky.social @uofgmvls.bsky.social
Huge congratulations to Emma Davis, the winner of 2025's Early Career Microbiologist of the Year prize! We agree with Emma that all of the finalists' talks were brilliant and a massive well done to everyone involved!
October 8, 2025 at 2:32 PM
🎉 Fletcher lab PhD student Emma Davies reflecting on her prize winning talk - we’re super proud of you Emma - many congrats! 🎉
@cvrinfo.bsky.social @uofgsii.bsky.social @uofgmvls.bsky.social
@cvrinfo.bsky.social @uofgsii.bsky.social @uofgmvls.bsky.social
Reposted by Fletcher Lab
Our work on the Panoptes antiphage system is published! Here we find that Panoptes "watches" the cytosol for phage immune evasion proteins–captured in this illustration by Clair Huffine of Insight Illustrations. A beautiful example of the effector triggered immunity paradigm.
October 8, 2025 at 11:14 AM
Our work on the Panoptes antiphage system is published! Here we find that Panoptes "watches" the cytosol for phage immune evasion proteins–captured in this illustration by Clair Huffine of Insight Illustrations. A beautiful example of the effector triggered immunity paradigm.
Reposted by Fletcher Lab
Viro3D paper is out! We predicted 85,000 protein structures from human & animal viruses. 1/5 🧵
📑 Paper doi.org/10.1038/s443...
🔭 Explore virosphere viro3d.cvr.gla.ac.uk
📑 Paper doi.org/10.1038/s443...
🔭 Explore virosphere viro3d.cvr.gla.ac.uk
Viro3D: a comprehensive database of virus protein structure predictions | Molecular Systems Biology
imageimageViro3D provides proteome-level, high confidence AI-protein structure predictions for
>4,400 viruses, allowing mapping of form and function across the human and animal
virosphere. Viro3D i...
doi.org
September 26, 2025 at 2:06 PM
Viro3D paper is out! We predicted 85,000 protein structures from human & animal viruses. 1/5 🧵
📑 Paper doi.org/10.1038/s443...
🔭 Explore virosphere viro3d.cvr.gla.ac.uk
📑 Paper doi.org/10.1038/s443...
🔭 Explore virosphere viro3d.cvr.gla.ac.uk
Reposted by Fletcher Lab
Allosteric activation of a ubiquitin ligase by an internal kinase domain! Congratulations to our team member Thornton Fokkens for this fascinating discovery in a neglected disease area with strong therapeutic need. Many thanks to all our great collaborators!
www.sciencedirect.com/science/arti...
www.sciencedirect.com/science/arti...
A Leishmania virulence factor harnesses an allosteric kinase switch to regulate its ubiquitin ligase activity
Stringent control of ubiquitylation is a central requirement of signaling specificity in eukaryotes. Here, we discover a domain module integrating pro…
www.sciencedirect.com
September 24, 2025 at 3:30 PM
Allosteric activation of a ubiquitin ligase by an internal kinase domain! Congratulations to our team member Thornton Fokkens for this fascinating discovery in a neglected disease area with strong therapeutic need. Many thanks to all our great collaborators!
www.sciencedirect.com/science/arti...
www.sciencedirect.com/science/arti...
Reposted by Fletcher Lab
🚨📝 New work via @thepandemicinst.bsky.social now preprinted!
We took ~19000 sequences of avian influenza virus and trained machine learning models on >40000 genomic/proteomic features - the resulting ensemble can predict zoonotic potential with AUC=0.95. More below!
www.biorxiv.org/content/10.1...
We took ~19000 sequences of avian influenza virus and trained machine learning models on >40000 genomic/proteomic features - the resulting ensemble can predict zoonotic potential with AUC=0.95. More below!
www.biorxiv.org/content/10.1...
An AI for an AI: identifying zoonotic potential of avian influenza viruses via genomic machine learning
Avian influenza remains a serious risk to human health via zoonotic transmission, as well as a feasible pandemic threat. Although limited zoonotic cases have resulted from the current epizootic outbre...
www.biorxiv.org
September 18, 2025 at 1:39 PM
🚨📝 New work via @thepandemicinst.bsky.social now preprinted!
We took ~19000 sequences of avian influenza virus and trained machine learning models on >40000 genomic/proteomic features - the resulting ensemble can predict zoonotic potential with AUC=0.95. More below!
www.biorxiv.org/content/10.1...
We took ~19000 sequences of avian influenza virus and trained machine learning models on >40000 genomic/proteomic features - the resulting ensemble can predict zoonotic potential with AUC=0.95. More below!
www.biorxiv.org/content/10.1...
Reposted by Fletcher Lab
A few months ago, our review “The Molecular Toolbox for Linkage Type-Specific Analysis of Ubiquitin Signaling” 🧬🧰🛠️ came out in ChemBioChem. Time to give it a spotlight!
chemistry-europe.onlinelibrary.wiley.com/doi/full/10....
chemistry-europe.onlinelibrary.wiley.com/doi/full/10....
September 16, 2025 at 7:45 AM
A few months ago, our review “The Molecular Toolbox for Linkage Type-Specific Analysis of Ubiquitin Signaling” 🧬🧰🛠️ came out in ChemBioChem. Time to give it a spotlight!
chemistry-europe.onlinelibrary.wiley.com/doi/full/10....
chemistry-europe.onlinelibrary.wiley.com/doi/full/10....
Reposted by Fletcher Lab
Had a brilliant time at the 9th International Calicivirus Conference in Banff (www.calicivirusconference.com) - phenomenal science in a phenomenal setting! It was great to present my PhD work so far (thanks @dbhella.bsky.social for the pic). Here's to many more!
September 13, 2025 at 6:41 AM
Had a brilliant time at the 9th International Calicivirus Conference in Banff (www.calicivirusconference.com) - phenomenal science in a phenomenal setting! It was great to present my PhD work so far (thanks @dbhella.bsky.social for the pic). Here's to many more!
Pre-print: our description of RZ affiliate ZNFX1 is now online.
On binding viral RNA, ZNFX1 generates parallel Ub currents, coordinating Ub-dependent RNA silencing and aggregate resolution.
Huge effort from first authors Dan Squair and @eilidhrivers.bsky.social
www.biorxiv.org/content/10.1...
On binding viral RNA, ZNFX1 generates parallel Ub currents, coordinating Ub-dependent RNA silencing and aggregate resolution.
Huge effort from first authors Dan Squair and @eilidhrivers.bsky.social
www.biorxiv.org/content/10.1...
ZNFX1 uses two-component ubiquitin circuitry to quarantine viral RNA
The detection of viral RNA inside cells triggers a diverse range of antiviral responses, including global translation inhibition, interferon secretion and RNA sequestration. Mutations in the gene ZNFX...
www.biorxiv.org
September 8, 2025 at 1:53 PM
Pre-print: our description of RZ affiliate ZNFX1 is now online.
On binding viral RNA, ZNFX1 generates parallel Ub currents, coordinating Ub-dependent RNA silencing and aggregate resolution.
Huge effort from first authors Dan Squair and @eilidhrivers.bsky.social
www.biorxiv.org/content/10.1...
On binding viral RNA, ZNFX1 generates parallel Ub currents, coordinating Ub-dependent RNA silencing and aggregate resolution.
Huge effort from first authors Dan Squair and @eilidhrivers.bsky.social
www.biorxiv.org/content/10.1...
Reposted by Fletcher Lab
So excited to see our newest study out in print! Led by the brilliant @jgezelle.bsky.social and @sophiekorn.bsky.social, we discovered how viruses from highly divergent families converge on a shared RNA structure mechanism to inhibit cellular nucleases. #RNAsky #LoveVirology
Our study from the Steckelberg lab is out now in @narjournal.bsky.social !! We dove into a new nuclease-blocking viral #RNA structure important for viral infection, which provided evidence of similar structure-based strategies across diverse viral families. academic.oup.com/nar/article/...
A conserved viral RNA fold enables nuclease resistance across kingdoms of life
Abstract. Viral exoribonuclease-resistant RNA (xrRNA) structures block cellular nucleases to produce subgenomic viral RNAs during infection. High sequence
academic.oup.com
September 4, 2025 at 8:54 PM
So excited to see our newest study out in print! Led by the brilliant @jgezelle.bsky.social and @sophiekorn.bsky.social, we discovered how viruses from highly divergent families converge on a shared RNA structure mechanism to inhibit cellular nucleases. #RNAsky #LoveVirology
Reposted by Fletcher Lab
Glad to share the final version of our story about the UBR4 complex, an E4 ligase protein quality control hub @science.org. Now with more cryo-EM structures and a deeper dive into substrate recognition, especially escaped mitochondrial proteins @clausenlab.bsky.social www.science.org/doi/10.1126/...
August 28, 2025 at 6:54 PM
Glad to share the final version of our story about the UBR4 complex, an E4 ligase protein quality control hub @science.org. Now with more cryo-EM structures and a deeper dive into substrate recognition, especially escaped mitochondrial proteins @clausenlab.bsky.social www.science.org/doi/10.1126/...
Reposted by Fletcher Lab
Happy to share our work on the structure and function of the unusual E3 ligase ZNFX1 @cp-cell.bsky.social. It uses a nucleic acid-activated transthiolation mechanism, ubiquitinating and clustering RNA to protect cells in an immune response. @clausenlab.bsky.social
www.cell.com/cell/fulltex...
www.cell.com/cell/fulltex...
A split-site E3 ligase mechanism enables ZNFX1 to ubiquitinate and cluster single-stranded RNA into ubiquitin-coated nucleoprotein particles
Grabarczyk et al. show the structure and mechanism of a non-canonical ubiquitin ligase,
which is activated through nucleic-acid-induced oligomerization and is critical for
cell survival during immune ...
www.cell.com
August 27, 2025 at 7:04 PM
Happy to share our work on the structure and function of the unusual E3 ligase ZNFX1 @cp-cell.bsky.social. It uses a nucleic acid-activated transthiolation mechanism, ubiquitinating and clustering RNA to protect cells in an immune response. @clausenlab.bsky.social
www.cell.com/cell/fulltex...
www.cell.com/cell/fulltex...
Opening for a biochemist to help us in the characterisation of novel ubiquitin-based antivirals. Diverse backgrounds welcomed; a keen sense of adventure is a must 😁
Details and criteria are below; please get in touch with any questions.
www.jobs.gla.ac.uk/job/research...
Details and criteria are below; please get in touch with any questions.
www.jobs.gla.ac.uk/job/research...
Research Assistant/Associate
Research Assistant/Associate COLLEGE OF MVLSSchool of Infection & ImmunityResearch and TeachingGRADE 6/7 Job PurposeThe post holder will join the School of Infection & Immunity, MRC-Univers...
www.jobs.gla.ac.uk
August 25, 2025 at 12:34 PM
Opening for a biochemist to help us in the characterisation of novel ubiquitin-based antivirals. Diverse backgrounds welcomed; a keen sense of adventure is a must 😁
Details and criteria are below; please get in touch with any questions.
www.jobs.gla.ac.uk/job/research...
Details and criteria are below; please get in touch with any questions.
www.jobs.gla.ac.uk/job/research...
Reposted by Fletcher Lab
Post 5/5 🧵
IMPACT: This transforms tick-borne disease research:
🎯 New drug targets
🎯 Understanding vector competence
🎯 Virus-tick evolution
Testing if mechanisms work across other tick viruses next.
👨🔬 collaborative project with @alf-castello.bsky.social and @alainkohlvirology.bsky.social
IMPACT: This transforms tick-borne disease research:
🎯 New drug targets
🎯 Understanding vector competence
🎯 Virus-tick evolution
Testing if mechanisms work across other tick viruses next.
👨🔬 collaborative project with @alf-castello.bsky.social and @alainkohlvirology.bsky.social
August 13, 2025 at 12:32 PM
Post 5/5 🧵
IMPACT: This transforms tick-borne disease research:
🎯 New drug targets
🎯 Understanding vector competence
🎯 Virus-tick evolution
Testing if mechanisms work across other tick viruses next.
👨🔬 collaborative project with @alf-castello.bsky.social and @alainkohlvirology.bsky.social
IMPACT: This transforms tick-borne disease research:
🎯 New drug targets
🎯 Understanding vector competence
🎯 Virus-tick evolution
Testing if mechanisms work across other tick viruses next.
👨🔬 collaborative project with @alf-castello.bsky.social and @alainkohlvirology.bsky.social
Reposted by Fletcher Lab
A few years back we discovered a dual hybrid protein modification composed of ADP-ribose dinucleotide and ubiquitin (ADPr-Ub). Now we reveal that ADPr-Ub can be further ubiquitinated by the E3 ubiquitin ligase RNF114!
www.nature.com/articles/s41...
www.science.org/doi/10.1126/...
www.nature.com/articles/s41...
www.science.org/doi/10.1126/...
Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose - Nature Communications
Deltex E3s modify ADP-ribosylated targets with ubiquitin, creating a hybrid modification whose readers remains unknown. Here, the authors synthesise a non-hydrolysable probe that mimics the modificati...
www.nature.com
July 10, 2025 at 6:11 AM
A few years back we discovered a dual hybrid protein modification composed of ADP-ribose dinucleotide and ubiquitin (ADPr-Ub). Now we reveal that ADPr-Ub can be further ubiquitinated by the E3 ubiquitin ligase RNF114!
www.nature.com/articles/s41...
www.science.org/doi/10.1126/...
www.nature.com/articles/s41...
www.science.org/doi/10.1126/...
Reposted by Fletcher Lab
How predictable are the evolutionary pathways leading to insecticide resistance? Why do some species gain resistance while others do not? We explore these questions in our latest preprint. A huge effort from Rebecca Frkic, Alex Giang, Colin Jackson and the team.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
July 8, 2025 at 11:05 PM
How predictable are the evolutionary pathways leading to insecticide resistance? Why do some species gain resistance while others do not? We explore these questions in our latest preprint. A huge effort from Rebecca Frkic, Alex Giang, Colin Jackson and the team.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by Fletcher Lab
We are looking for a PhD student in (mostly )wet-lab biochemistry to work on short linear motifs, intrinsically disordered regions, in the context of the Marie Curie network "IDPro". More info an apply here: www.uu.se/en/about-uu/...
PhD student in Biochemistry - Uppsala University
PhD student in Biochemistry, Disciplinary Domain of Science and Technology, Faculty of Chemistry, Department of Chemistry - BMC, Uppsala University
www.uu.se
June 30, 2025 at 8:39 AM
We are looking for a PhD student in (mostly )wet-lab biochemistry to work on short linear motifs, intrinsically disordered regions, in the context of the Marie Curie network "IDPro". More info an apply here: www.uu.se/en/about-uu/...
Reposted by Fletcher Lab
postdoc opening in vienna: study lipid droplets (LDs) with integrative structural biology, uncover how LD proteins shuttle between cytosol & nucleus to regulate lipid metabolism, organelle architecture and immune response. #VIP3 #lipidtime #cryoEM #coffee training.vbc.ac.at/post-docs/vi...
VIP³ Post Doc Program (2025 - 2030)
VIP3 is a postdoctoral fellowship program at the Vienna BioCenter offering three – year fellowships that are open to candidates with backgrounds in life sciences, chemistry, physics, medicine, enginee...
training.vbc.ac.at
June 24, 2025 at 9:03 PM
postdoc opening in vienna: study lipid droplets (LDs) with integrative structural biology, uncover how LD proteins shuttle between cytosol & nucleus to regulate lipid metabolism, organelle architecture and immune response. #VIP3 #lipidtime #cryoEM #coffee training.vbc.ac.at/post-docs/vi...
Reposted by Fletcher Lab
🚨🚨 News from the @castello-lab.bsky.social and @shabazlab.bsky.social. Our work, led by Louisa Iselin, reveals pervasive changes in the RNA-bound proteome induced by interferon. #RNA, #immunity, #interferon, #host-virus www.biorxiv.org/content/10.1...
June 3, 2025 at 10:01 PM
🚨🚨 News from the @castello-lab.bsky.social and @shabazlab.bsky.social. Our work, led by Louisa Iselin, reveals pervasive changes in the RNA-bound proteome induced by interferon. #RNA, #immunity, #interferon, #host-virus www.biorxiv.org/content/10.1...
Reposted by Fletcher Lab
OMG! I can finally share my joy to see my SFTSV work published in @natcomms.nature.com! This adventure started by the award of my MSCA grant and my move to the Kohl and @brennanlab.bsky.social at @cvrinfo.bsky.social. Let's chat about how we discovered novel tick anti-viral effectors!
Multi-omics analysis of SFTS virus infection in Rhipicephalus microplus cells reveals antiviral tick factors - Nature Communications
Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) is a deadly tick-borne virus and a growing global health threat. In this study, Petit et al. used a multi-omics approach on SFTSV-infected tic...
www.nature.com
May 23, 2025 at 2:02 PM
OMG! I can finally share my joy to see my SFTSV work published in @natcomms.nature.com! This adventure started by the award of my MSCA grant and my move to the Kohl and @brennanlab.bsky.social at @cvrinfo.bsky.social. Let's chat about how we discovered novel tick anti-viral effectors!
Reposted by Fletcher Lab
Happy that my work on RNF213 has been published as a part of doi.org/10.1038/s414...!
Many thanks to all the groups involved:
@clausenlab.bsky.social
@e3chembio.bsky.social
@fletcherlab.bsky.social
Have a look at the summary from Fletcher lab for an insider perspective of the paper's history:
Many thanks to all the groups involved:
@clausenlab.bsky.social
@e3chembio.bsky.social
@fletcherlab.bsky.social
Have a look at the summary from Fletcher lab for an insider perspective of the paper's history:
May 22, 2025 at 12:37 PM
Happy that my work on RNF213 has been published as a part of doi.org/10.1038/s414...!
Many thanks to all the groups involved:
@clausenlab.bsky.social
@e3chembio.bsky.social
@fletcherlab.bsky.social
Have a look at the summary from Fletcher lab for an insider perspective of the paper's history:
Many thanks to all the groups involved:
@clausenlab.bsky.social
@e3chembio.bsky.social
@fletcherlab.bsky.social
Have a look at the summary from Fletcher lab for an insider perspective of the paper's history:
Reposted by Fletcher Lab
Sharing the next installment of our fun collaboration with @michaelnadbio.bsky.social at the interface of #ubiquitin and #ADP-ribosylation! Building upon our identification of cellular MARUbylation, we now identify reader/writer E3 ligases that extend K11 polyUb! 🧵
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
A family of E3 ligases extend K11 polyubiquitin on sites of MARUbylation
Ubiquitin (Ub) cooperation with other post-translational modifications provides a tiered opportunity for protein regulation. Small modifications to Ub such as phosphorylation, acetylation, or ADP-ribo...
www.biorxiv.org
May 17, 2025 at 2:45 PM
Sharing the next installment of our fun collaboration with @michaelnadbio.bsky.social at the interface of #ubiquitin and #ADP-ribosylation! Building upon our identification of cellular MARUbylation, we now identify reader/writer E3 ligases that extend K11 polyUb! 🧵
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by Fletcher Lab
Excited to share our new paper on Nature - how Ku accommodates Alu expansion in primates by binding to dsRNA, providing a clue for both the high levels of Ku and its essentiality in human cells. Thank @chaolinzhang @hchung03 @LenaSteckelberg More to come www.nature.com/articles/s41...
Ku limits RNA-induced innate immunity to allow Alu-expansion in primates - Nature
Nature - Ku limits RNA-induced innate immunity to allow Alu-expansion in primates
www.nature.com
May 16, 2025 at 11:11 PM
Excited to share our new paper on Nature - how Ku accommodates Alu expansion in primates by binding to dsRNA, providing a clue for both the high levels of Ku and its essentiality in human cells. Thank @chaolinzhang @hchung03 @LenaSteckelberg More to come www.nature.com/articles/s41...