From structure to soul: New research project sheds light on proteins in motion
How can we understand the soul of a protein? That is the question Professor Gregers Rom Andersen finds himself asking after 35 years of mapping the physical structures of proteins. When a single sample unexpectedly reveals ten distinct conformations, it becomes clear: molecules hold more than just form — they hold motion, time, and perhaps something deeper. Now, he embarks on a new journey: to understand how proteins live their lives.
From snapshots to molecular life stories
With decades of experience in structural biology, Professor Gregers Rom Andersen has provided the scientific world with detailed insights into the atomic architecture of proteins using techniques like X-ray crystallography and cryo-electron microscopy (cryo-EM). But now, his research is shifting focus — toward what he himself calls “the soul of molecules.”
Until recently, the protein structures mapped by Gregers Rom Andersen and his team represented frozen snapshots — fixed conformations captured at a single moment in time. But breakthroughs in cryo-EM have made it possible to visualize multiple states from the same sample. One such revelation marked a turning point:
“Within the last year, I had a sample that gave me ten or more conformations. It was an explosion of knowledge,” he explains. “But it also raised the question: which of these states actually exist in living cells — and for how long?”
This realization led to a profound shift: from examining static structure to exploring protein movement through time and space. Not just what proteins are — but what they become. As he puts it:
“I’ve spent 35 years understanding the architecture of molecules. Now it’s time to understand their soul.”
This transformation is not just driven by technological progress, but also by the collective efforts of his long-standing research group:
“I’ve been fortunate to have an extraordinary team over the years. It’s their skill and persistence that brought us to this point,” says Andersen. “We’ve built an environment where precision and curiosity go hand in hand.”
Time-resolved research at the molecular level
Collaboration is key. At Aarhus University’s iNANO center, Associate Professor Victoria Birkedal specializes in advanced techniques for tracking biomolecular dynamics in real time. Andersen saw the opportunity to combine his structural expertise with these dynamic methods — to measure the lifespans of conformations and how they interconvert.
Together with Birkedal’s team and an international partner, Andersen will lead the new project Time-resolved studies of complement activation and phagocytosis, which will explore the immune system’s complement pathways and phagocytosis — and how proteins morph during these vital processes.
The project has been awarded DKK 11.4 million by the Novo Nordisk Foundation through a Distinguished Investigator grant. It will run for five years from 1 September 2025 and includes PhD and postdoctoral researcher Marlene Fruergaard as part of the team.
New perspectives on classic methods
This venture is not just a broadening of Andersen’s personal research — it’s a reflection of a broader shift in modern structural biology. Where protein structures were once seen as static models, they are now increasingly viewed as part of a continuum of movements, where function depends on flexibility and transition.
It is in these transitional states — between forms, between functions — that the “soul” of molecules may be hiding.
“For the first time, we have the tools to ask questions we simply couldn’t ask before,” Andersen says. “And that opens the door to entirely new insights.”
Want to learn more about Gregers Rom Andersen’s grant and the other research projects funded alongside it?
Check out the article “Three Researchers, Three Paths – One Strong Research Culture”, where we introduce the three grant recipients and their scientific visions.