Fletcher Lab

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

248 followers352 following35 posts

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Receptor clustering is a common theme in viral detection, but whether detection directly hinders genome replication is less clear. Excited to share the Z in RZ-type E3s: ZNFX1 is an RNA helicase that builds ubiquitin chains leading to aggregates that ensnare viral RNA. www.cell.com/molecular-ce...

cell.comZNFX1 uses two-component ubiquitin circuitry to quarantine viral RNASquair et al. show that ZNFX1 restricts ssRNA virus replication by integrating SF1 helicase activity with dual E3 ligase mechanisms. ATP-dependent RNA binding activates E3 function, driving self-propa...

Huge congratulations, Lillie and team!

Lillie Bell@lilliebell.bsky.social

Happy to share my PhD work on the regulatory mechanism of E3 ligase RNF213! RNF213 is not a monomer, but a dimer that switches between inhibited and activated states in an ATP-dependent manner. We tracked the activation mechanism and showed how disease mutations can destabilize the inhibited state.

Fletcher Lab reposted

Those little c-terminal tails, which sit at the opposite end of the OAS2 molecule from the site of (essential) co-translational lipidation, seem to hold the secret of split function.

Emma decided to pursue this anyway and, after astutely not listening to my advice and heeding the thoughts of wiser virologists, Emma discovered that OAS2 achieves something apparently quite unique.

Of two near-identical ~70 kDa isoforms that differ only by 4-/36-length c-terminal tails, only one restricts HCoV-OC43, while the other restricts cardiovirus A/Encephalomyocarditis virus. The shorter, anti-OC43 isoform restricts independently of 2-5A synthesis and RNase L.

Emma then moved to our group after the Wilson Lab relocated to Cambridge, and we began an iterative process of whittling down the screen to tractable targets for investigation.

OAS2 seemed an unlikely hit because HCoV-OC43, unlike some more distantly related betaCoVs e.g. SARS-CoV-2, encodes a phosphodiesterase (PDE). betaCoV PDEs are known to inhibit the OAS-RNase L pathway, an ancient antiviral partnership that relies on synthesis and detection of 2'-5'-oligoadenylates.

Emma began her PhD in Sam Wilson's group at the CVR, where she and Sam developed an elegant approach for screening dsRNA in virus-infected cells in high throughput. Emma then used the famous Wilson Lab ISG screens to start screening for factors that inhibit human seasonal coronavirus, HCoV-OC43.

Fletcher Lab reposted

Our work on the role of Ufmylation on ribosome quality control on the ER is out! Great work of two terrific first authors Milica and @alessandrick.bsky.social together with our wonderful collaborators, the one and only Dagdas lab @plantophagy.bsky.social!

Max Perutz Labs Vienna@maxperutzlabs.ac.at

🆕 publication! The @gekaragoz.bsky.social lab shows how cells clear stalled ribosomes at the ER, preventing harmful 'traffic jams' during protein synthesis🚦Their new @embojournal.org study reveals how quality control and UFMylation team up to keep translation moving ➡️ tinyurl.com/2czj8fvp

Receptor clustering is a common theme in viral detection, but whether detection directly hinders genome replication is less clear. Excited to share the Z in RZ-type E3s: ZNFX1 is an RNA helicase that builds ubiquitin chains leading to aggregates that ensnare viral RNA. www.cell.com/molecular-ce...

cell.comZNFX1 uses two-component ubiquitin circuitry to quarantine viral RNASquair et al. show that ZNFX1 restricts ssRNA virus replication by integrating SF1 helicase activity with dual E3 ligase mechanisms. ATP-dependent RNA binding activates E3 function, driving self-propa...

Fletcher Lab reposted

Fletcher Lab reposted

🧐 What if metabolic defects are not just a consequence of inflammatory disease - but actively contribute to it? Inflammation and metabolism are deeply intertwined, but the molecular links remain unclear. Our new paper in Cell Death & Differentiation uncovers one. 🧵👇 nature.com/articles/s41...

Fletcher Lab reposted

I have multiple positions available to join my lab from this summer: #postdoc, #student and #technician. Adverts to follow but see www.saurinlab.com for further details. #senescence, #mitosis, #cellcycle, #phosphorylation are the key areas. Email me if interested.

Fletcher Lab reposted

Hello 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!

Alice Wicks@ubch-alice.bsky.social

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...

Fletcher Lab reposted

Fletcher Lab reposted

🎉 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

Microbiology Society@microbiologysociety.org

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!

Fletcher Lab reposted

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.

Fletcher Lab reposted

Fletcher Lab reposted

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...

sciencedirect.comA Leishmania virulence factor harnesses an allosteric kinase switch to regulate its ubiquitin ligase activityStringent control of ubiquitylation is a central requirement of signaling specificity in eukaryotes. Here, we discover a domain module integrating pro…

Fletcher Lab reposted

Fletcher Lab reposted

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

Jeanine Gezelle@jgezelle.bsky.social

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/...

Fletcher Lab reposted

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...

jobs.gla.ac.ukResearch Assistant/AssociateResearch 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...

Fletcher Lab reposted

Fletcher Lab reposted

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/...

uu.sePhD student in Biochemistry - Uppsala UniversityPhD student in Biochemistry, Disciplinary Domain of Science and Technology, Faculty of Chemistry, Department of Chemistry - BMC, Uppsala University