Stephen Graham's Lab
@atomicvirology.bsky.social
Lab in the University of Cambridge 🇬🇧 studying the cell biology, biophysics and structural biology of virus infection. Blame Stephen 🇦🇺 for the content.
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!
I think we're ready for the lab summer garden party!
August 9, 2025 at 11:42 AM
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!
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!
July 27, 2025 at 9:59 AM
Great job @danielacl.bsky.social presenting this work at #IHW2025. Missed the talk? You can still catch her at poster 3.14 this evening!
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.
July 27, 2025 at 8:12 AM
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.
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.
July 27, 2025 at 8:12 AM
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.
July 27, 2025 at 8:12 AM
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.
July 27, 2025 at 8:12 AM
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.
July 27, 2025 at 8:12 AM
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.
We showed a few years ago that HSV pUL21 is a PP1 adaptor protein, directing dephosphorylation of cellular and viral proteins, and that PP1 recruitment requires a novel motif: TROPPO (a tenuous bacronym 😉)
July 27, 2025 at 8:12 AM
We showed a few years ago that HSV pUL21 is a PP1 adaptor protein, directing dephosphorylation of cellular and viral proteins, and that PP1 recruitment requires a novel motif: TROPPO (a tenuous bacronym 😉)
Barnstorming talk by @danandviruses.bsky.social on his work looking at HSV infection is neurons and its ability to alter neuronal firing 💯👏
Missed the talk? You can still catch Dan at his poster tomorrow night (3.59). #IHW2025
Missed the talk? You can still catch Dan at his poster tomorrow night (3.59). #IHW2025
July 26, 2025 at 7:42 AM
Barnstorming talk by @danandviruses.bsky.social on his work looking at HSV infection is neurons and its ability to alter neuronal firing 💯👏
Missed the talk? You can still catch Dan at his poster tomorrow night (3.59). #IHW2025
Missed the talk? You can still catch Dan at his poster tomorrow night (3.59). #IHW2025
July 25, 2025 at 1:01 PM
Great talks by Colin @campathology.bsky.social , Dima @cambiochem.bsky.social and the facility manager Luay
May 14, 2025 at 12:57 PM
Great talks by Colin @campathology.bsky.social , Dima @cambiochem.bsky.social and the facility manager Luay
Gearing up with a 🍕 lunch before the PaCIFiC imaging facility launch at @campathology.bsky.social
www.path.cam.ac.uk/research/fac...
www.path.cam.ac.uk/research/fac...
May 14, 2025 at 11:21 AM
Gearing up with a 🍕 lunch before the PaCIFiC imaging facility launch at @campathology.bsky.social
www.path.cam.ac.uk/research/fac...
www.path.cam.ac.uk/research/fac...
Newspapers: This has been both the wettest and driest March on record, with drought and floods in Europe, and temperatures 1.6C above pre-industrial levels
Also newspapers:
Also newspapers:
April 8, 2025 at 6:59 AM
Newspapers: This has been both the wettest and driest March on record, with drought and floods in Europe, and temperatures 1.6C above pre-industrial levels
Also newspapers:
Also newspapers:
Celebratory dinner for the @campathology.bsky.social crew at #microbio25 to celebrate fabulous talks and poster presentations!
April 2, 2025 at 8:03 PM
Celebratory dinner for the @campathology.bsky.social crew at #microbio25 to celebrate fabulous talks and poster presentations!
It's not too late to see @danandviruses.bsky.social talk about hsv infection in neurons at #Microsoc25 - come to hall 11a+b at 15:21 today!
April 2, 2025 at 1:45 PM
It's not too late to see @danandviruses.bsky.social talk about hsv infection in neurons at #Microsoc25 - come to hall 11a+b at 15:21 today!
Including some blasts from the past @chillzaa.bsky.social
March 29, 2025 at 10:36 AM
Including some blasts from the past @chillzaa.bsky.social
Excited to be hosting "our grow your own protein crystal" at the Cambridge Festival @campathology.bsky.social
March 29, 2025 at 9:53 AM
Excited to be hosting "our grow your own protein crystal" at the Cambridge Festival @campathology.bsky.social
Huge congratulations to Dani for winning the Alan Monroe prize for best student poster at the @campathology.bsky.social annual research symposium💯👏🍾🎉!
Curious 🤔? She'll be presenting it again at #Microbio25 next week... Come see what all the buzz is about!
Curious 🤔? She'll be presenting it again at #Microbio25 next week... Come see what all the buzz is about!
March 26, 2025 at 5:10 PM
Huge congratulations to Dani for winning the Alan Monroe prize for best student poster at the @campathology.bsky.social annual research symposium💯👏🍾🎉!
Curious 🤔? She'll be presenting it again at #Microbio25 next week... Come see what all the buzz is about!
Curious 🤔? She'll be presenting it again at #Microbio25 next week... Come see what all the buzz is about!
Great talk by @danandviruses.bsky.social about his PhD work on HSV infection in neurons at the @campathology.bsky.social annual symposium 💯🤓
March 26, 2025 at 4:40 PM
Great talk by @danandviruses.bsky.social about his PhD work on HSV infection in neurons at the @campathology.bsky.social annual symposium 💯🤓
Beware of falling rocks...
March 24, 2025 at 7:33 AM
Beware of falling rocks...
Great live demonstration of how election microscopy works, and the signal to noise challenge in atomic imaging, at @doryenbubeck.bsky.social's inaugural lecture #imperialinaugural
March 12, 2025 at 5:51 PM
Great live demonstration of how election microscopy works, and the signal to noise challenge in atomic imaging, at @doryenbubeck.bsky.social's inaugural lecture #imperialinaugural
This work has been a fabulous partnership between @campathology.bsky.social (esp. Monique) and Brazil, especially Eurico @ University of São Paulo. Thanks also to colleagues @ Rosalind Franklin Institute who made the nanobodies and @royalsociety.org for funding this equitable research partnership.
March 2, 2025 at 1:39 PM
This work has been a fabulous partnership between @campathology.bsky.social (esp. Monique) and Brazil, especially Eurico @ University of São Paulo. Thanks also to colleagues @ Rosalind Franklin Institute who made the nanobodies and @royalsociety.org for funding this equitable research partnership.
We demonstrated that our nanobodies can directly block OROV infection, so could be used as direct acting antiviral compounds. Additionally, they can be used in lab-based studies to detect specific OROV antigens, so will help accelerate research into this understudied virus.
March 2, 2025 at 1:39 PM
We demonstrated that our nanobodies can directly block OROV infection, so could be used as direct acting antiviral compounds. Additionally, they can be used in lab-based studies to detect specific OROV antigens, so will help accelerate research into this understudied virus.
We also showed that these OROV antigens can raise a potent neutralising (infection-blocking) immune response in mice, suggesting that our OROV antigens could be used as immunogens in a future OROV vaccine.
March 2, 2025 at 1:39 PM
We also showed that these OROV antigens can raise a potent neutralising (infection-blocking) immune response in mice, suggesting that our OROV antigens could be used as immunogens in a future OROV vaccine.