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Chris H. Hill

@chillzaa.bsky.social

1.9K followers 740 following 41 posts

Wellcome Sir Henry Dale Fellow and PI at the University of York, UK. He/him 🏳️‍🌈 Interested in #RNA, #ribosomes, #cryo-EM, #crystallography and #virus gene expression, 🔬🧬 https://www.hill-lab.co.uk Also piano 🎹🎶 www.youtube.com/@chillzaa

www.hill-lab.co.uk

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Chris H. Hill @chillzaa.bsky.social · Nov 13

I'm a structural and molecular biologist and research group leader. We work on mechanisms of pathological translation in viral infection (e.g. IRES initiation, frameshifting, stop codon readthrough). Interested in RNA biology, ribosomes, host-pathogen interactions and regulation of gene expression.

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Chris H. Hill @chillzaa.bsky.social · 1d

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

Chris H. Hill @chillzaa.bsky.social · 1d

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

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...

www.biorxiv.org

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Chris H. Hill @chillzaa.bsky.social · 1d

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

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Chris H. Hill @chillzaa.bsky.social · 1d

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

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Chris H. Hill @chillzaa.bsky.social · 1d

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)

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Chris H. Hill @chillzaa.bsky.social · 1d

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

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Chris H. Hill @chillzaa.bsky.social · 1d

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...

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...

www.biorxiv.org

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Reposted by Chris H. Hill

Oli Clarke @olibclarke.bsky.social · 25d

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

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Chris H. Hill @chillzaa.bsky.social · Jul 30

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 🧬🔴🟢

Steve Quinn @steve-quinn-lab.bsky.social · Jul 30

🚨 New preprint!🚨We introduce a DNA-scaffold strategy for efficient dye labelling of structured RNAs, enabling #smFRET studies of freely-diffusing SARS-CoV-2 pseudoknots🧬
👉 biorxiv.org/content/10.1...

#smFRET #RNA #biophysics #SARSCoV2 #singlemolecule #Covid

A DNA scaffold approach facilitates 5′ labelling of the SARS-CoV-2 RNA pseudoknot for smFRET investigation

Single-molecule Förster resonance energy transfer (smFRET) studies of highly structured RNA molecules are often frustrated by issues with efficient dye conjugation. Here, we develop a DNA scaffold-bas...

biorxiv.org

Chris H. Hill @chillzaa.bsky.social · Jul 21

Thanks Dan :)

Chris H. Hill @chillzaa.bsky.social · Jul 21

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