Chris H. Hill

MRC DiMeN Doctoral Training Partnership: Understanding molecular mechanisms of protein-primed genome replication in enteroviruses at University of York on FindAPhD.com PhD Project - MRC DiMeN Doctoral Training Partnership: Understanding molecular mechanisms of protein-primed genome replication in enteroviruses at University of York, listed on FindAPhD.com

🚨👇One week left to apply for this fully-funded PhD project to study RNA-protein complexes regulating enterovirus genome replication:

www.findaphd.com/phds/project...

chris hill PhD Projects, Programmes & Scholarships - 3 PhDs Listed FindAPhD. Search Funded PhD Projects, Programmes & Scholarships in chris hill. Search for PhD funding, scholarships & studentships in the UK, Europe and around the world.

🚨Attention prospective PhD students🚨
Are you interested in molecular mechanisms, RNA viruses, structural biology or biophysics? 🧬🦠🧪

We have THREE fully-funded PhD projects available for October 2026 entry:
www.findaphd.com/phds/?Keywor...

Please share/repost, and get in touch if you're interested

chris hill PhD Projects, Programmes & Scholarships - 3 PhDs Listed FindAPhD. Search Funded PhD Projects, Programmes & Scholarships in chris hill. Search for PhD funding, scholarships & studentships in the UK, Europe and around the world.

🚨Attention prospective PhD students🚨
Are you interested in molecular mechanisms, RNA viruses, structural biology or biophysics? 🧬🦠🧪

We have THREE fully-funded PhD projects available for October 2026 entry:
www.findaphd.com/phds/?Keywor...

Please share/repost, and get in touch if you're interested

This was a fantastic collaboration with the groups of @valerialulla.bsky.social @campathology.bsky.social and Trevor Sweeney @pirbrightinst.bsky.social. Thanks also to superb colleagues and facilities @biologyatyork.bsky.social, YSBL, @ybri-uoy.bsky.social and @diamondlightsource.bsky.social

The mechanism of ribosomal recruitment during translation initiation on Type 2 IRESs The encephalomyocarditis virus (EMCV) IRES and other Type 2 IRESs comprise domains H-L and specifically interact with eIF4G/eIF4A through their essential JK domain. However, the JK domain is not suffi...

These findings are similar to recent work on the EMCV Type 2 IRES — see e.g. www.biorxiv.org/content/10.1...; www.biorxiv.org/content/10.1... — and suggest that common structural motifs and mechanisms may exist within highly divergent picornavirus IRES sequences

To validate our structures, in collaboration with @valerialulla.bsky.social @campathology.bsky.social
, we carry out targeted disruption of domain IVc in related enterovirus CVA13. These mutations are highly detrimental to viral translation and replication in both HeLa and HIEC6 cell lines

IRES domain IVc contacts uS19 and uS13 on the 'head' of the small ribosomal subunit, whilst the conserved apical GNRA tetraloop interacts directly with the initiator tRNA

In our preprint, we reconstitute human translation initiation on a model poliovirus IRES and examine 48S complexes by cryo-EM. Our structures reveal a network of interaction between IRES domain IVc and the translation machinery during start-codon recognition (closed 48S complexes)

Enteroviruses use an internal ribosome entry site (IRES) within the 5′ UTR to recruit the translation machinery. Type 1 IRESs are large (~450 nt), flexible RNAs that require numerous eIFs and the host factor PCBP2 — making them very challenging structural targets

Structural and mechanistic insights into translation initiation on the enterovirus Type 1 IRES Enteroviruses are a widespread and diverse set of pathogens responsible for over ~1 billion human infections annually. Upon cell entry, translation of the virus genome is mediated by an internal ribos...

Enteroviruses cause over a billion infections each year, but the details of how their genomes capture host ribosomes have remained elusive. I'm pleased to share a new preprint from Miguel in our group, providing some new insights into this problem:
www.biorxiv.org/content/10.1...

This one is a bit of a departure from the usual and definitely a work in progress!

We found that by using ab initio reconstruction at very high res, in very small steps, we could crack some small structures that had eluded us - e.g. 39kDa iPKAc (EMPIAR-10252), below.

Read on for details... 1/x

Ever struggled with low PNK efficiency on a highly structured piece of RNA? Sarah solved this problem by using a DNA scaffold to make the 5' end more accessible, improving the efficiency of end labelling. This enabled us to make smFRET measurements on the SARS-CoV-2 pseudoknot 🧬🔴🟢

Thanks Dan :)

Thanks Ahmad, it was great to see you again too :)

Thanks also to the superb facilities at @biologyatyork.bsky.social, YSBL and @ybri-uoy.bsky.social, light source access @diamondlightsource.bsky.social and DESY, and to our funders, including @wellcometrust.bsky.social @royalsociety.org, BBSRC, EPSRC, DiMEN DTP and @thelisterinstitute.bsky.social

This was a fun collaboration with the brilliant
@steve-quinn-lab.bsky.social Mark Leake, @timcraggs.bsky.social, as well as Ian Brierley and @atomicvirology.bsky.social at @campathology.bsky.social

We explore the mechanism in detail, and make the argument that this represents a new class of protein-dependent riboswitch. It's perhaps useful to think about other frameshifting signals in a similar way - especially those with reported conformational plasticity.

Amazingly, this is not a stable structure. We use SAXS and single molecule FRET to show that the existence of this pseudoknot is entirely dependent on the 2A protein - without it, the RNA stays as a stem-loop, unable to activate frameshifting.

Here we present the structure of the 2A-RNA complex at 1.9 Å, revealing a novel RNA pseudoknot 👇

During virus genome translation, ribosomes encounter an unusual blockage: a complex between a structured RNA element and the mysterious viral 2A protein. This complex is essential to activate frameshifting, but how does it work?

Many RNA viruses use programmed -1 ribosomal frameshifting as an essential gene expression strategy. Cardioviruses (e.g. EMCV, TMEV) are the absolute masters of this, causing ~85 % of ribosomes to 'slip' into the -1 reading frame.

A new protein-dependent riboswitch activates ribosomal frameshifting Programmed -1 ribosomal frameshifting (PRF) is a ubiquitous translational control mechanism in RNA viruses, allowing them to change the relative abundance of proteins encoded in different reading fram...

New preprint alert! 🚨👇 I'm delighted to share the latest research from @jemmabetts.bsky.social
in our group: ‘A new protein-dependent riboswitch activates ribosomal frameshifting’. Huge congratulations to Jemma for the first manuscript of her PhD! ✨

www.biorxiv.org/content/10.1...

Thanks so much Dan, yes would be great to catch up soon😀

I'm thrilled and honoured to receive the 2025 Lister Prize, along with seven other fantastic biomedical scientists 🔬🦠🧬

This award will enable us to determine high-resolution structures of viral protein synthesis inside infected cells

George M. Sheldrick (1942–2025) In memory of George Sheldrick.

A tribute to George Sheldrick and SHELX and the impact on macromolecular and small-molecule crystallography

journals.iucr.org/a/issues/202...

Last day to apply for the CCP4 Structural Biology Summer School 2025! 31 July to 8 August at University of York. The programme will focus on X-ray crystallography but many model-building, refinement and validation aspects also relevant to cryo-EM 💎❄️

ccp4.github.io/summer-schoo...

a cartoon of snoopy jumping with the words yay congratulations below him ALT: a cartoon of snoopy jumping with the words yay congratulations below him

Congratulations to Dr Sarah Graham @york.ac.uk #Physicsoflife group for successfully defending her thesis!
Thanks also to Dr Tara Sabir & @agnesnoy.bsky.social for doing the honours as examiners, @bpsiyork.bsky.social for co-supervising & @chillzaa.bsky.social for all the help along the way!

Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex. By integrating cryo–electron microscopy single-particle analysis and cryo–electro...

Excited to share our new @science.org paper! Led by postdocs Ruchao Peng and Xin Xu, we used cryo-EM/ET to reveal the influenza ribonucleoprotein complex structure and its strand-sliding mechanism for RNA synthesis, paving the way for new antivirals.
www.science.org/doi/10.1126/...

a little É(as)tude... 🎹🐣
Happy holidays everyone!

It's here. The lumicks C-Trap is up and running with real samples from Durham, Hull, Newcastle and York consortium. Thanks @ukri.org #BBSRC for funding.
@chillzaa.bsky.social