“I don’t think it happens very often but my experience shows that if you want it to, then it can – it’s just about putting yourself out there and asking for the opportunity”

Natural Sciences undergraduate Ella de Csilléry was a first year at St John’s when she became involved in research with the potential to transform the treatment of cancer and other diseases – and even reveal the origins of life on Earth. She tells Karen Clare what it was like.

Ella was studying Physics, Chemistry, Biology of cells and Maths in 2019 when she decided to try to get some summer experience in a lab before her second year, and sent speculative emails to several St John’s Fellows.

Professor Tuomas Knowles was the first to reply and offer a placement. His lab is a multi-disciplinary group doing pioneering research into disorders such as Alzheimer’s to develop new techniques for early diagnosis and treatment, so it was a thrilling prospect.

“I was introduced to two researchers from the Knowles Lab, who later supervised me, and was sent some reading material over that year,” said Ella, from London. “Then, in the summer, I turned up at the lab with not too much idea of how it would pan out, I was just really eager to get involved in as many things as possible.”

In fact, the now 20-year-old was to be involved in a research project that spanned the globe. During a phase separation experiment – in which two phases (in this case liquids rather than solids or gases) are created from a single homogeneous mixture – she witnessed a surprising chemical reaction.

“One of my supervisors was explaining to me how phase separation works, and gave me a quick demonstration. He put two liquids together in a combination Ella’s summer lab work leads to world-class research Natural Sciences undergraduate Ella de Csilléry was a first year at St John’s when she became involved in research with the potential to transform the treatment of cancer and other diseases – and even reveal the origins of life on Earth. She tells Karen Clare what it was like. where you might expect them not to phase-separate – but when we looked, the liquid was cloudy. He said, ‘hang on, that’s not what we expect to happen’. Under the microscope we could see the liquid had phase-separated, and that discovery kicked off further investigation, because we discovered that this happened not only in a low salt regime, as predicted, but also in a high salt regime,” said Ella. “It was very exciting.”

The research showed for the first time that liquid-like protein compartments, known as condensates, in cells can re-enter a phase-separation regime in response to different salt concentrations. Cells contain proteins and other biomolecules that must be carefully organised for them to function properly. Condensates remain segregated through the physics of phase separation, like oil and water. In a changed salt environment, the cell can trigger the formation or dissolution of these protein-rich liquids. Sometimes, these components can go wrong, which can be implicated in diseases such as cancer and Alzheimer’s. The findings may help scientists develop future patient therapies – and could even tell us how life began and evolved in Earth’s salty oceans.

Ella was listed among the contributing authors of a research paper published in Nature Communications in February, beside her supervisors Dr Georg Krainer and Timothy Welsh, two of the lead co-authors. Cambridge’s Collepardo Lab, which uses computational physics to research chromatin – the substance within a chromosome consisting of DNA and protein – was also involved in the research, along with scientists from the Technical University in Dresden, the Max Planck Institute of Molecular Cell Biology and Genetics, and the University of Toronto.

“Everyone was so enthusiastic and supportive, it was an amazing experience”

Ella spent eight weeks in the lab, helping to pull together supporting evidence and working on other projects. It is quite unusual for an undergraduate to be involved in such ground-breaking research, not to mention a first year. “I don’t think it happens very often but my experience shows that if you want it to, then it can – it’s just about putting yourself out there and asking for the opportunity,” said Ella. “I appreciate I was really lucky but I wouldn’t have got that chance if I hadn’t asked. First years may not realise they have those opportunities available to them at Cambridge.

“I really enjoyed the amount of collaboration. It was great to have the opportunity to work in Professor Knowles’s lab and to have my work published. Everyone was so enthusiastic and supportive, it was an amazing experience.”

Professor Knowles said: “It was a great pleasure to host Ella in our lab. We are always keen to host exceptionally talented summer students for short research projects, and Ella’s work was truly impressive. She managed to obtain remarkable new results in her project focusing on understanding the molecular mechanisms of biomolecular condensate formation, and these formed an integral part of a Nature Communications paper that Ella contributed to, based on this work.”

Last year Ella applied for summer lab work at universities in the US and received two offers, although sadly the pandemic meant she was unable to go. She plans to study a fourth year at St John’s to get her Natural Sciences part III, and is now considering graduate medicine. A singer in St John’s Voices, Ella also plays the violin and College lacrosse when she isn’t playing her part in potentially life-saving research.

Learn more about the research.

*This article first appeared in the Easter Term 2021 edition of Eagle Eye.*

Published: 1/7/2021

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