In conversation with Chris Hill

Dr Chris Hill, Lister Prize Fellow 2025, is a structural biologist and virologist at the University of York. His research explores how RNA viruses hijack the machinery of human cells, with a particular focus on enteroviruses.

We caught up with Chris to discuss his scientific journey, his team’s latest discoveries, and the impact of the Lister Prize on his work.

Q: What first drew you to a career in science?

A: I’ve always been curious about how things work. My parents both studied science, so there was a lot of encouragement at home – whether it was building cardboard inventions or tinkering with electronics. At school, I was drawn to chemistry for its mechanistic explanations, but it was during my undergraduate studies at Cambridge that I discovered the fascination of molecular biology and biochemistry. The idea that you could visualise molecules at the atomic level, especially using techniques like X-ray crystallography and later cryo-EM, really captured my imagination. That sense of discovery – of seeing how the fundamental machinery of life fits together – has never left me.

Q: What excites you most about working at the interface of biochemistry, structural biology, and virology?

A: It’s incredibly rewarding to bring together different disciplines to answer complex questions. Structural biology is a craft in itself, but the real breakthroughs often come when you collaborate with experts in virology, biochemistry, and beyond. I’ve been fortunate to work in environments – like Cambridge and York – where multidisciplinary research is encouraged and where you can build networks with people who have mastered their own crafts. That collaborative spirit is essential, especially as the questions we’re asking become more ambitious and technically challenging.

Q: Can you tell us about your lab’s current research on enteroviruses and why it matters?

A: Our main focus is on how enteroviruses – an important group of human pathogens that include poliovirus and rhinovirus – hijack the host’s ribosomes to make their own proteins. This process, called translation initiation, is a critical step in the viral life cycle. Unlike human mRNAs, enteroviral RNAs use highly structured regions called internal ribosome entry sites (IRES) to recruit ribosomes. Understanding exactly how this works is not just a fascinating scientific problem; it’s also medically significant. Enteroviruses cause a huge burden of disease worldwide, from the common cold to more severe conditions like viral meningitis and polio. Yet, we still lack targeted antivirals that disrupt viral protein synthesis.

Our lab uses a combination of in vitro reconstitution, cryo-electron microscopy (cryo-EM), and in situ structural biology to dissect these mechanisms. We’re also developing new models to study viral translation in the context of infected cells, which is a major step forward for the field.

These insights were made possible by combining advanced structural techniques with functional assays, such as dual-luciferase reporter systems and viral replication models.

Q: Tell us more about your switch to in situ structural biology. What is this technique, and what do you hope it will reveal?

A: In situ structural biology is a relatively new approach that allows us to visualise molecular machines directly within intact, frozen cells – rather than extracting and purifying them for study in a test tube. The process involves growing cells on specialised electron microscopy grids, infecting them with virus, and then rapidly freezing them to preserve their native state. We then use focused ion beam milling to thin the cells, making them suitable for high-resolution imaging by cryo-EM.

What’s so exciting about this technique is that it lets us see how viral and host molecules interact in their natural environment, surrounded by all the complexity of the cell. For example, we can capture the precise, dynamic molecular contacts that are essential for viral protein synthesis in near real-time. This is something that’s very difficult to achieve with traditional in vitro methods, which can miss important cellular factors or transient interactions.

By applying in situ structural biology, I hope we’ll be able to answer longstanding questions about how viral translation is regulated inside infected cells. We want to see, in real time, how the viral RNA manipulates the host’s machinery, and identify any unique features that could be targeted by new antiviral drugs. Ultimately, this approach could help us move beyond static snapshots and build a much more complete, dynamic picture of infection – one that could inform both fundamental biology and the development of new therapies.

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The Lister Prize has been transformative. The flexibility of the funding means we can take risks and pursue new directions that would be difficult with more traditional grants._”

Q: How has winning the Lister Prize made a difference to your research and your team?

A: The Lister Prize has been transformative. The flexibility of the funding means we can take risks and pursue new directions that would be difficult with more traditional grants. For example, we’re able to invest in developing in situ structural biology workflows and support team members to learn new techniques or spend time with collaborators at other institutions. The five-year funding horizon is also significant – it gives us the breathing space to tackle ambitious projects and support the career development of our students and postdocs.

Just as importantly, being part of the Lister community has opened up new networks and collaborations. The annual meetings are a highlight, bringing together scientists from diverse fields who are all passionate about pushing the boundaries of biomedical research.

Q: What advice would you give to early-career researchers thinking of applying for the Lister Prize?

A: Don’t be afraid to propose bold ideas, even if you don’t have all the preliminary data yet. The Lister Prize is unique in its willingness to support innovative, high-risk projects – especially if you can demonstrate a strong collaborative network and a clear vision. I found the application process very supportive, with opportunities to update your proposal and suggest reviewers who understand your approach. And once you’re part of the community, there’s a real sense of mutual support and knowledge-sharing.

Q: What are the biggest questions you hope to answer in the next few years?

A: There’s still so much we don’t know about how viral RNAs manipulate host translation machinery. For example, how do ribosomes choose between different start sites on viral RNAs? What conformational changes occur during the initiation process, and how are these regulated by host and viral factors? Advances in imaging and AI-driven structure prediction are opening up new possibilities, but there’s still a need for high-resolution experimental data – especially for dynamic, flexible RNA structures.

Ultimately, our goal is to map out the entire process of viral translation initiation in situ, within the context of an infected cell. This could reveal new therapeutic targets and help us understand how viruses evolve to evade host defences.