Exeter College Fellow co-leads study revealing how virus-like particles assemble

Exeter College Official Fellow and Lecturer in Physical Chemistry and Professor of Chemistry, Philipp Kukura, has co-led a new study revealing how virus-like particles can spontaneously assemble from their individual components. 

The research, published in Nature, provides a molecular-level view of how the protein shells associated with viruses can reliably form, despite the thousands of possible ways their individual components could fit together. 

Viruses protect their genetic material inside precisely organised protein shells called capsids. Understanding how these structures assemble – and what can disrupt the process – could ultimately contribute to the development of new antiviral treatments, vaccines, and other therapies. 

Professor Kukura and the Oxford team studied an engineered virus-like particle made from 60 protein units. They combined mass photometry, a technology developed at Oxford which measures the mass of individual molecules, with a method for confining individual molecules so that they could be observed continuously. 

This allowed the researchers to effectively ‘weigh’ individual particles repeatedly as new protein components joined them, revealing the assembly process step by step. 

The study found that protein building blocks initially form weak, reversible connections, allowing unsuccessful arrangements to separate and try again. Once particular closed structures form, however, their multiple connections make them much more stable, creating molecular ‘waypoints’ that progressively guide the process towards a completed particle. 

Professor Kukura said: “Until now, much of our understanding of how these structures assemble has had to be reconstructed from snapshots or theoretical models. Being able to both quantify the underlying interactions and follow one particle as it grows changes that.”