Why would you want to devote years of your life to a seemingly meaningless protein in baker's yeast? Or on the way a single-celled parasite dresses up its DNA? Group leader Fred van Leeuwen must have been asked these question many times throughout his life. And if not, he must have at least seen it in the eyes of the people with whom he shared his work. But his research – as well as the passing of time – has shown how fundamental discoveries in microorganisms like those mentioned above are crucial for the development of innovative applications in medicine.
Our fundamental understanding of cells is surprisingly incomplete, for example. We still only partially understand how the cells in our body work. How do they, for example, evolve into very different cells while having the same DNA code. A skin cell is not a heart cell, and a brain cell can’t be mistaken for a gut cell. "That's what the packaging of the DNA does," says Van Leeuwen, professor by special appointment of Cellular Epigenetics at the University of Amsterdam.
"The packaging of the DNA determines the fate of a cell by dictating which genes are switched on, and when. We call this epigenetics. And although we are now quite familiar with this packaging, we still don't fully understand how all its parts interact with each other, and with other parts of the cell nucleus. There’s an interesting challenge in this interaction. We really need to keep returning to these foundations in order to move forward in science and medicine."
"Fundamental research can take unexpected turns," Van Leeuwen knows. And there is a tremendous strength in that. By pursuing his curiosity in baker's yeast cells, for example, he discovered how a protein called Dot1 can change the packaging of DNA. "This protein now appears to be an interesting target for leukemia treatment, and we are investigating whether we can use this knowledge to improve cancer immunotherapy."
Fundamental research has been crucial to our increasing understanding of epigenetics in recent decades, so to speak. Van Leeuwen: "There are hundreds of examples that show how fundamental research, covering a variety of topics ranging from petunias to calico cats, unraveled how and why genes turn on and off. None of those researchers started with the question of how to treat cancer, but we can now use their tools to advance cancer research."
Van Leeuwen still returns to the single-celled organisms where it all started for him three decades ago. "We need to develop new techniques to get a solid grip on the way genes switch on and off," he says, "and that's perfectly doable in baker's yeast."
Van Leeuwen even sees his work impact the world outside his lab. As an educator, for example, he regularly helps students at a nearby high school with their final project. "Most of them have no idea what they want to do with their lives. Some of them want to go into the life sciences after their project and a visit to our lab, which I find wonderful. I have since had mothers approach me in tears, saying, ‘Thank you, this is huge: my daughter knows what she wants to do now!’ Those moments are amazing.”