Fletcher Lab
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
- Reposted by Fletcher LabHello world! I am excited to announce my lab is open at the University of Utah in the Department of Biochemistry. We are looking for scientists at all levels interested in studying host-virus interactions in both bacteria and animals. Come join us in beautiful Utah! (photo is 10 steps from lab)
- Super new paper from @ubch-alice.bsky.social and Danny Huang @cruk-si.bsky.social – a great deal of hard work and development behind this story. From a technical perspective, this reads as a primer for tapping 'unconventional' E3s. Very well done Alice and team!
- My first-author paper is out in @chemicalscience.rsc.org from my time in Professor Danny Huang’s laboratory @cruk-si.bsky.social. We showed that CBL can be used as a degrader E3 to target the “undruggable” eIF4E. pubs.rsc.org/en/content/a...
- Reposted by Fletcher LabExcited to share our work into ubiquitin E1-E2 specificity mechanisms. CryoEM visualising #ubiquitin transfer,biochemistry,evolution @labhofmann.bsky.social & tissue expression analyses @psarkies.bsky.social Big thanks to the team,reviewers & handling editor @dimitristypas.bsky.social rdcu.be/eTRdR
- We’re thrilled to onboard Alice Wicks @ubch-alice.bsky.social in the lab this week. Alice trained with Danny Huang @cruk-si.bsky.social and has developed exciting new ideas for co-opting E3s for targeted degradation. Welcome to the team, Alice.
- Reposted by Fletcher LabWe’ve made some new tools to manipulate N-recognins. Check them out in our preprint. www.biorxiv.org/content/10.1...
- 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.
- Reposted by Fletcher LabExcited 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....
- 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...
- Reposted by Fletcher LabA #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
- Reposted by Fletcher LabOur 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 LabViro3D 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
- Reposted by Fletcher LabAllosteric 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...
- 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...
- Reposted by Fletcher LabA 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....
- Reposted by Fletcher LabHad 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...
- Reposted by Fletcher LabSo 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 LabGlad 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 LabHappy 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...
- 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...
- Reposted by Fletcher LabPost 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
- Reposted by Fletcher LabA 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/...
- Reposted by Fletcher LabHow 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...
- Reposted by Fletcher LabWe 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 Labpostdoc 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...
- Reposted by Fletcher LabOMG! 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 LabHappy 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:
- Reposted by Fletcher LabSharing 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...
- Reposted by Fletcher LabExcited 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...
- A wee summary of our paper: Tim and Juraj’s landmark paper from 2020 was the first to elucidate the structural and biochemical detail of RNF213, the largest known E3 and only AAA-E3 hybrid. Among many observations, two stood out: E3 activity was RING-independent and specific for the E2 UBE2L3.
- Both observations formed key predictions that turned out to be true. Why a AAA ATPase had a built-in E3 was also a mystery. elifesciences.org/articles/56185
- Around this time we were profiling E3s regulated by interferon (IFN), identifying RNF213 using a cysteine-reactive activity-based probe (ABP). We’d tried to capture an RNF213-ABP complex with ATP to little effect. @petermabbitt.bsky.social suggested non-hydrolysable analogues. Floodgates opened.
-
View full threadThanks to all the many who contributed along the way and the very supportive editorial team @natcomms.nature.com (end).
- Great to see this out. A story that spanned continents, cities and budget codes… www.nature.com/articles/s41... Big thanks to all the teams involved! @clausenlab.bsky.social @e3chembio.bsky.social
- Reposted by Fletcher LabVery happy to see Honglin Chen's DPhil work and and @alf-castello.bsky.social passion project (aren't all projects passion projects in academia?) finally get published! www.mcponline.org/article/S153...
- Reposted by Fletcher LabUbiquitin & Friends Fiesta in Vienna 2025 -- Final Call despite these challenging times for science, we look forward to gather for a lively meeting and share the joy of discovery. to join an exciting program and connect with fellow ubiquitinists sign up at www.protein-degradation.org/symposium/
- Reposted by Fletcher LabNew in Nature Comms: We applied metagenomic + targeted NGS to serum from febrile patients in Uganda. Post-COVID, LMICs have sequencing infrastructure that could be repurposed for pathogen discovery. 🔗 www.nature.com/articles/s41...
- Reposted by Fletcher LabCome do a PhD with me using LLMs and comparative methods to understand the emergence of companion animal viruses! 🧠☠️🕸️🐕🐈🖥️ Fully funded 3.5 year PhD based at @sbohvm.gla.ac.uk and @cvrinfo.bsky.social supervised by myself, Margaret Hosie, and Willie Weir www.findaphd.com/phds/project...
- Reposted by Fletcher LabOnline now! @pottslab.bsky.social @amgen.bsky.social demonstrate proof-of-concept of disease-specific targeted degradation by redirecting virally encoded E3 ubiquitin ligases with VIPER-TACs. dlvr.it/TJLmvh
