Unravelling the hidden story of a protein
St Catherine’s College Associate Dean Dr Samuel Nonis Solves a 100-year-old scientific mystery
When people imagine scientific breakthroughs, they often picture dramatic medical advances or futuristic technology. Yet some of the most meaningful discoveries begin with simple curiosity and a question that seems almost too ordinary to matter. For Associate Dean Dr Samuel Nonis, one such question emerged from a tiny protein that had been sitting quietly in laboratory freezers for more than a century.
The protein is concanavalin A, commonly known as conA. Found in jack bean seeds, it is prized for its ability to bind sugars, making it a favourite in laboratories around the world. Scientists use conA to capture molecules, study cell surfaces and explore how sugars decorate proteins. Because of this, conA has become one of the most widely used plant proteins in modern biology.
In the mid-1980s, researchers made an unexpected discovery. The sequence of the conA protein did not match what its gene predicted. Somewhere in the plant, after the protein was produced, its order of amino acids changed. The middle became the ends and the ends became the middle. The rearrangement was so surprising that scientists jokingly referred to it as ‘protein carpentry’. Although this type of protein modification, known as circular permutation, later became a tool for protein engineering, conA remained the only natural example.
For almost forty years, no one knew why this rearrangement occurred or whether it served any purpose. The scientific community also knew very little about what conA looked like before the change. That unanswered question became the focus of Sam’s doctoral research.
While completing his PhD in structural biology at The University of Western Australia, Sam worked with collaborators to study both the unmodified protein, known as pro-conA and the enzyme responsible for reshaping it. The project required patience, precision and several complementary scientific techniques.
Sam and his team solved the atomic structure of pro-conA and also the structure of the jack bean enzyme thought to drive the rearrangement. With these insights, they recreated the entire transformation in the laboratory and confirmed that a single enzyme could cut the protein, reorder its sequence and form the bonds needed to complete the process.
The results revealed something remarkable. Pro-conA, the original form of the protein, is far less stable than the mature version. After circular permutation, conA becomes significantly more resistant to heat and acidity. The transformation does not change how it binds sugars, but it does influence how well the protein holds its shape under stress. What once seemed a biological curiosity now appears to give the protein a clear functional advantage.
Sam’s research was published in The Plant Cell, one of the most respected journals in plant science. It has since been highlighted in scientific summaries, featured in author interviews and examined in an independent commentary. The publication represents a significant achievement and offers new insight into a protein that has intrigued researchers for more than a century.
Sam’s academic journey reflects a deep interest in how genes and proteins shape life. During his Honours year with Professor Ryan Lister, he investigated targeted epigenetic modifications in the human genome. Sam later worked at Singapore’s Agency for Science, Technology and Research, applying molecular techniques to explore protein evolution. This experience deepened his interest in how structure shapes function and ultimately led him to structural biology and crystallography during his PhD.
Today Sam is the Associate Dean at St Catherine’s College Curtin. His connection to St Cat’s began years earlier as a resident and Residential Advisor at the UWA campus, giving him a strong understanding of College life and the experiences of the students he now supports.
Outside work, Sam enjoys camping with his two cats, usually with a good book in tow. Having grown up in the urban jungle of Singapore, he has developed a deep appreciation for the wide-open landscapes of Western Australia since moving here.
Whether in the laboratory or walking through the College courtyard, Sam brings the same curiosity and calm determination. His research revealed new insights into a protein that puzzled scientists for decades and at St Cat’s he guides residents through some of the most formative years of their lives. In both science and community, he shows the value of thoughtful questions, meaningful connections and noticing the details that others might overlook.
The full body of work for Sam’s discovery is available online:
Sam’s Author Profile (Plantae)
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