We are looking forward to welcoming Professor Tony Hyman to DPAG on 6 March, when he will deliver the 2025 Sir Wilfrid Le Gros Clark Price Lecture, speaking about phase separation in cell physiology and disease. Professor Hyman joins us from the Max Planck Institute of Molecular Cell Biology and Genetics, where his research has focussed on how cells form cellular compartments without a membrane.
In advance of his lecture here, we interviewed Professor Hyman to find out more about his career and research.
What first inspired you to become a scientist, and how did you come to choose and specialise in your area of research?
‘My path into research started when I interviewed as a PhD student in Cambridge. I came up for an interview at the LMB in the C. elegans group and could see I was not doing well until I ended up in John White's office. Everyone else seemed to be working on DNA, about which I had little interest, or training. John showed me pictures of C. elegans one cell stage embryos and I was hooked. I had taken a course in cell biology in my last year at UCL that had been very stimulating, and I was primed to find cell organization interesting. John did two other important things. He made me read the work of Viktor Nigon from the 1960s, requiring my rather rusty school boy French. Nigon and co-workers had laid out in beautiful detail how the first cell division was beautiful, reproducible and easy to follow. He also sent me to the Cambridge library, where I found a copy of EB Wilson from 1920, “the cell in development and heredity.” Opening this book was for me, in a minor way, like opening Tutankhamun’s tomb, in which the British archaeologist Howard Carter reported after being asked what he saw, replied “Wonderful things.” As I read the book, I too saw “Wonderful things.”’
In what ways can we see the real-world impact of your scientific research?
In 2000, my team pioneered the use of RNA interference to define the "parts lists" for different cytoplasmic processes. And in 2009, we, together with Cliff Brangwynne and Frank Julicher, made a fundamental breakthrough by being the first to observe that compartments in cells can form by phase separation.
We asked Professor Hyman where his current research is heading, he said, ‘The discovery of phase separation in cells was exciting because it suggested the same physics as used to study say cloud formation could be used to think about how cells form compartments. We are addressing three outstanding problems. The first is how molecular interactions give rise to mesoscale behaviour. We are used to thinking of molecular specificity in terms of tight interactions between molecular species as we might see in protein complexes. But in liquid condensates, interactions are transient. Where does specificity come from if interactions are so transient? A second area we work on is linking defects in phase separation to disease, what is being called a condensatopathy. And finally, do emergent properties of liquids, such as viscosity, surface tension and solvent properties help us understand biochemical regulation?’
We asked Professor Hyman what advice he might give to early career research scientists. He said, ‘At the LMB Laboratory of Molecular Biology[what is the full name please?], surrounded as I was by molecular approaches, I was astonished when I opened the book “The Cell in Development and Heredity” to read all the amazing mesoscale cell biology that had been summarized in the 1920s by EB Wilson, and then effectively largely forgotten. This is a common theme in discovery in the biomedical sciences, as new ways of looking at the world led science to veer off in a certain new direction: Virgin territory is full of exciting discoveries for young people, and it allows them to escape the control of the seniors who are working in more old-fashioned subjects. A modern example is enzymology, which was a hot field in the 1970s, but became less and less worked on as molecular biology got started. But there is value in later generations returning to ideas from the literature and renewing work on them with new tools and approaches, exactly as is now happening in enzymology.
‘Having passed my 60th birthday, it is indeed wonderful to see young people tackling the problem of emergent properties of cellular compartments, and to see people from different fields coming together to bring their expertise, especially from polymer and soft matter physics. Quite often they are delving into literature that is many decades old. Together they are trying to answer the key question of how evolution worked with basic physical chemical principles such as phase separation to create a cell with robust biochemistry. The great hope is that cells have worked out physical mechanisms that allow such precise control, which we have not identified simply by working with dead matter.’