Stephen Graham's Lab

This is a lab biochemicals quiz. Seriously, that's the kind of thing I come up with in my spare time. I know, it's weird, right?

You might have missed out on our lab Christmas party this year, but you can still try your hand at our "common lab chemicals" quiz. Apparently me handing out a sheet of chemical drawings is 'not fun', so this year we also had cryptic clues...

EM is the culprit this time... At least it didn't also send me a new login and password (for once!)

a man in a purple robe is sitting on a set of stairs surrounded by two women . ALT: a man in a purple robe is sitting on a set of stairs surrounded by two women .

Definitely not you Alain! My beef isn't with the timing of the request, we all need to get things done as and when we can, it's the reminder on a Sunday morning that seems tone deaf...

Surely it can't be hard to update the code to send a reminder on the n+2 work day...

Seriously @plos.org - what is the deal with sending a review request at 8 pm on a Friday night and then following up on Sunday morning if people have had the temerity to not respond over the weekend to a request for free labour?

The infamous virology Christmas party rides again!

Top UK scientist says research visa restrictions endanger economy Prof Sir Paul Nurse says the UK is "shooting itself in the foot" with its visa system for researchers.

BBC News - Top UK scientist says research visa restrictions endanger economy
www.bbc.com/news/article...

Raccoon gets drunk at Ashland ABC store and passes out in bathroom Talk about a trashed panda.

Raccoon gets drunk at a Virginia liquor store and passes out in bathroom

Viral protease-mediated polyprotein processing in human astroviruses Positive-sense RNA viruses often encode large polyproteins that are proteolytically processed by viral and host proteases into functional replication proteins. Astroviruses infect intestinal and neuro...

📢Astrovirus polyprotein processing is finally uncovered - these viruses use peculiar dual cleavage sites around their protease! Led by a talented PhD student, David Noyvert, this work provides a map of astrovirus genomes. Great collaboration with @emmottlab.bsky.social @leandroxneves.bsky.social

Nah, probably the end of the road for us with this particular project (blame UKRI)

Just published in JBC @asbmbjournals.bsky.social - HSV-1 pUL21 teaches us that the universe of protein phosphatase 1 (PP1) binders may be much larger than previously recognised: www.jbc.org/article/S002...

Bluetorial at bsky.app/profile/atom...

Viruses - is there anything they can't do? 🦠💪

Come and join us here in Cambridge! Applications open for a new faculty position, for a researcher in computational and/or theoretical biology, based jointly in Genetics and Mathematics. Happy to answer questions about research, teaching and working here.

www.cam.ac.uk/jobs/faculty...

I love AlphaFold—but please include PAE (Predicted Aligned Error) plots for every “interaction.” Pretty PDBs ≠ proof. If the PAE doesn’t show an interface, it ain’t one. Show the plots. Structural biology's reputation is on the line.

Earlier this year we took our Escape Lab outreach activity on the road, funded by @microbiologysociety.org & @biochemsoc.bsky.social Outreach Grants. We had a blast teaching kids about viruses & the drug discovery process. Check out how Microbiology Society's Adam & Clare got on with Escape Lab!

Understanding the future risk of bat coronavirus spillover into humans: correlating sarbecovirus receptor usage, host range, and antigenicity. Sarbecoviruses interact with their receptor, angiotensin converting enzyme 2 (ACE2), via the receptor binding domain (RBD) of Spike, the immunodominant target for neutralising antibodies. Understandin...

Our first post on here and it's a doozy 😍🤩. Our epic piece on #sarbecovirus host range. #virology #sars2 #covid #vaccines. Enjoy and please repost. www.biorxiv.org/content/10.1...

They even made an interactive evidence map:
research.ukhsa.gov.uk/evidence-gap...

Particularly relevant on a day when the first reports have emerged of imported Oropouche cases in the UK:
www.gov.uk/government/n...

Oropouche virus: a rapid evidence gap map This rapid evidence gap map identifies and categorises the available evidence on Oropouche virus to inform research prioritisation.

#Oropouche virus news!! @ukhsa.bsky.social has mapped the evidence for Oropouche virus epidemiology, vectors and ecology, virology, pathogenesis, medical countermeasures and public health:
www.gov.uk/government/p...

An incredibly useful resource to guide future research and funding

Now published in @embomolmed.org 🥳🎉
Protein-based tools for detection and characterisation of #Oropouche virus infection...
See the final paper at doi.org/10.1038/s443... and read the bluetorial 👇

It's a lie....🤫

Fridge is stacked, marquee is up, house didn't need cleaning because it's always super tidy...😬🤥
I think we're ready for the lab summer garden party!

Great job @danielacl.bsky.social presenting this work at #IHW2025. Missed the talk? You can still catch her at poster 3.14 this evening!

Want to know more? Come to the talk by @danielacl.bsky.social today at #IHW2025 (room 2 at 11:39) or come to her poster tonight (number 3.14).

a man in a tuxedo is applauding in front of a crowd of people ALT: a man in a tuxedo is applauding in front of a crowd of people

Congratulations to primary authors Holly and @danielacl.bsky.social on their first first-author research papers. This work was a fun collaboration with @deanelab.bsky.social, and many thanks to @bsfcharity.bsky.social for funding.

While pUL21 doesn’t bind a new surface on PP1, so no new antiviral drugs 😢, we have identified a new mode of PP1 binding via an extended beta sheet…this binding of a protein with no canonical SLiMs to PP1 suggests there might be many more PP1 adaptors in the cell than previously suggested.

a cartoon of a wizard with the words you 've come to the right place ALT: a cartoon of a wizard with the words you 've come to the right place

Why would a virus keep a suboptimal RVxF motif rather than evolve higher affinity? We hypothesise that it is an additional layer of regulation, make sure that PP1 recruitment only happens in the right place, and at the right time post-infection, when local concentrations of pUL21/pORF38 are high.

However, the affinity of pORF38 for PP1 is ~10-fold lower than for some cellular PP1 binders. This is because these pUL21 and pORF38 residues structurally corresponding to the RVxF motif have non-optimal sequences. Mutating these residues to make a canonical RVxF motif enhances PP1 binding.

Using fluorescence polarization, we showed the TROPPO peptide alone is not enough to bind PP1, you need the whole protein. Also, we show that VZV pORF38 directly competes with cellular RVxF+ϕϕ[xF] motif containing peptides for binding the RVxF motif.

This explains why deleting a chunk of the linker between the pUL21 N-terminal domain (NTD) and the TROPPO motifs abolishes PP1 binding, why our previous TROPPO mutations prevent binding (they would block packing of the TROPPO and the pUL21 NTD), and new mutations further supported the #AF3 models.

Using #AlphaFold3, we predicted the structure of HSV-1 pUL21 and VZV pORF38 in complex with PP1. Surprisingly, the TROPPO motif binds the same hydrophobic groove as cellular RVxF and ϕϕ[xF] motifs. Strikingly, a disordered linker region of pUL21 is predicted to become ordered upon PP1 binding.

a close up of a man wearing glasses and a wig . ALT: a close up of a man wearing glasses and a wig .

This TROPPO motif is conserved across the alphaherpesviruses, but it doesn’t resemble any of the known PP1 binding motifs (RVxF, SILK, ϕϕ[xF], etc.). Does that mean pUL21 and homologues bind PP1 via a novel surface, that could be targeted with antiviral drugs?