Source: NEMO Kennislink / Michelle Wijma
Officially, Jan van Hest carries the title of professor of bio-organic chemistry. Unofficially, he's an architect. He often likens the cells he creates to building a house. The cell nucleus? That's the library. "All the blueprints and instructions (DNA) are stored there," he explains. "Then you have mitochondria-the power supply, just like the fuse box and radiators in a house. Waste management? In a house, that's the toilet and the garbage bin; in a cell, lysosomes do the job."
And the doors and windows? "They decide who or what can get in or out. A cell manages that with receptors in the membrane. Some require you to ring the bell with a special molecule, while others are left slightly ajar." Just like a house has different rooms, a cell is divided into compartments. "Without them it would be chaos," says Van Hest. "Imagine putting the boiler in the library-your books would be up in flames before you know it."
Cytoskeleton
The professor's latest construction isn't a new room but the structural support that keeps the house from collapsing. Together with his research team, Van Hest designed a synthetic cytoskeleton. "It's the foundation and load-bearing walls of the cell. The big difference with a house, though, is that a cytoskeleton is dynamic. The walls of a cell can shift position and shape." This constant motion means the cytoskeleton not only provides strength, but also shapes a cell's behavior and communication. "It determines, for example, what shape the cell can take. A muscle cell needs to stretch far, while an immune cell needs to be able to 'swallow' intruders."
Bringing cells to life
It's around this point that the architect metaphor collapses. Van Hest doesn't just want a house that stands firm-he wants one that strolls off, splits in two, and chats with the neighbors. In other words, his dream-shared by many scientists-is to bring his cells to life.
"A cell is, at its core, just a little sphere built from molecules. A chemist can put that together too, but what you get then is something inert, not alive. So what is it that makes a cell live, divide, communicate, and evolve?"
That mystery is what drives him. "Only when you can build it, can you truly understand it. And along the way, we learn an incredible amount. For instance, our constructions are already being used to deliver medicines exactly where they're needed in the body, like into cancer cells."
What is it that makes a cell live, divide, communicate, and evolve?
Jan van Hest
Building a house takes a lot of laying bricks, sawing, and drilling. But how does Van Hest actually piece together his cells? The method sounds almost disarmingly simple. "We make the individual building blocks of the cell and bring them together. Under the right conditions, the molecules then organize themselves. Within minutes, they form the structures we're after."
The Billy bookcase
It's as if you tossed the parts of an IKEA kit into the air and the shelves and screws clicked together on their own. "That's the big challenge. Our building blocks only become a cell if we feed them the right information."
For example: molecule A clicks into molecule B like a puzzle piece. Together they latch onto molecule C, which then sheds a fragment. "The more modules you add, the more interactions are possible-including ones you don't want. Even the simplest artificial cell is deeply complex, made up of millions of modules."
The synthetic cytoskeleton Van Hest's team designed is built from polymers that the cell spontaneously absorbs, which then form tiny fibers. "Through interactions with the cell, the fibers bundle into larger structures that take on the desired cytoskeleton properties."
Van Hest describes his field of research as a remarkable world of discovery. "We pour endless time into designing and crafting the building blocks, but once you have them, it's just a matter of combining-and voilà, there's your cell." If only the same could be said of a Billy bookcase.
Feelers
When Van Hest was eight, he didn't dream of becoming an architect-he wanted to be a lawyer. He laughs. "It's just as well that phase passed. I would have struggled defending someone whose actions I had moral objections to. Criminal lawyers are vital, but I'd rather leave that to someone else."
A new fascination emerged in high school, one that stuck for life. "My first chemistry class felt like coming home. I understood molecules. They helped me make sense of the world around me. Take fire, for example. Suddenly I understood where those flames came from, and everything that happens in that fire."
Stepping into my first chemistry class felt like coming home.
Jan van Hest
The spark truly ignited when Van Hest went on to study chemical engineering in Eindhoven. After that, things moved fast. He was only 31 when he became a professor in 2000-and it happened almost by accident. Van Hest applied for a position at Radboud University that he thought he wasn't qualified for. "My goal was just to signal that I was considering a return to academia. At the time, I was working at DSM, becoming more of a manager, and wasn't sure I even wanted that path." He laughs. "That interview turned out to be the most relaxed one I've ever had. I wasn't the right candidate anyway."
Young professor
The university did hire someone else, but they were impressed by Van Hest. They carved out a spot for him as a young professor. "They gave me five years to build my research group. It was perfect for figuring out if I really wanted to be an academic-but it was stressful, too."
Thrown in at the deep end, the fresh-faced chemist had zero experience in teaching or writing research proposals. "I was a rookie in a field full of established names, but with some help from colleagues, we managed to build momentum."
Return to Eindhoven
In 2016, Van Hest returned to Eindhoven as a professor of bio-organic chemistry. He radiates care for his research team, making sure everyone feels safe and at home within it. During the annual group outing, his feelers are especially alert. "I make sure everyone feels involved and enjoys themselves. Seeing that social cohesion and the sheer fun the group has-it really makes me happy."
Van Hest also loves traveling with his family. He and his partner and daughter explored China together. "We saw incredible things, like the Terracotta Army near Xi'an and the Summer Palace in Beijing. Next on our travel list are Indonesia and Costa Rica."
Better than expected
One thing that truly excites Van Hest is the enthusiasm of his younger colleagues. "A successful experiment gives you a real rush. Celebrating victories together is hugely motivating. You have to have a certain temperament to be a scientist, I think-you also have to handle the failures, because many things don't work out."
A successful experiment gives you a real rush.
Jan van Hest
Sometimes what seems like a failure turns out even better than expected. That's exactly what happened during the design of the cytoskeleton polymers. Van Hest explains: "We hoped the molecules would spontaneously take on the right structure-and they did. What we didn't anticipate was that we could control where in the cell the cytoskeleton would assemble."
The chemists discovered this by accident after tweaking the fibers to make them easier to decorate with interesting molecules. "With that adjustment, the fibers suddenly moved toward the cell's surface. So we can choose! No adjustment: the skeleton forms in the center. Adjustment applied: it forms at the edge."
Van Hest is excited about the period ahead. "We're in the middle of a generational shift. Many people are finishing their time with us, while new researchers are joining. It's a perfect moment to reflect." The professor wants to gain even greater control over the behavior of artificial cells. "How can we get them to cooperate better, with each other and with living tissue? I'm looking forward to reaching that higher level of function and complexity."
