’Sometimes things go wrong, but how bad is that really?’

Build big with the smallest parts. Scientists move molecules towards life. But what motivates them? In this episode of A Spark of Life: Luc Brunsveld.

/ Michelle Wijma

As a child, Luc Brunsveld dreamed of becoming a reverend - someone who could inspire others and guide them in their personal growth. Fast forward to today: instead of the pulpit, he found his calling in the lab, as a professor of Chemical Biology at Eindhoven University of Technology. Quite the career twist, isn’t it?

The turning point came when a young Luc Brunsveld realized that subjects like history and languages didn’t really hold his attention. Was theology still the right path for him? "The science subjects were more exciting," he recalls. "I especially loved chemistry - drawing molecules, imagining how they interact." In his final years of secondary school, the decision became clear: Brunsveld enrolled in the Chemical Engineering program in Eindhoven.

Rapid rise Brunsveld moved swiftly through his academic career. He earned his PhD cum laude at the age of 25, completed a postdoctoral fellowship, and took a brief detour into the pharmaceutical industry to get a taste of life outside academia. Not long after, he moved to Germany with his young family to launch his own research group - all before his thirtieth birthday. In 2008, four years later, he returned to Eindhoven as a newly appointed professor.

Molecular glue Luc Brunsveld is in the business of handcuffing disease-causing proteins. That’s the idea, at least. By linking two proteins together, both lose their function - effectively disabling them. The molecules Brunsveld and his team design to do this job are what he calls molecular glue . "Imagine someone sprinting away," he explains. "You chase them down, grab hold, and slap on the cuffs. Suddenly, both of you stop. That’s exactly how our molecular glue works."

Find the right kind of "cuffs" - the right molecular glue - and you could be holding the key to a powerful new drug. The glue forces the targeted proteins to stop functioning, which can have life-saving effects. For example, it could block proteins that cause cells to divide rapidly. Left unchecked, such runaway cell division is a key driver behind the development of cancer.

According to Brunsveld, the concept is now on solid footing. "We’re currently testing the glue in cells and animal models to see whether it has the desired biological effects," he says.

Alzheimer’s frontier

The next step is to push the concept further toward real-world treatments. To move in that direction with purpose, Brunsveld and a group of colleagues launched a start-up: Ambagon Therapeutics. "We collaborate with researchers from around the globe," he says, "including experts in fields like diabetes and Alzheimer’s disease." One promising avenue: using molecular glue to prevent the buildup of proteins between nerve cells - sticky clumps known as plaques, which are believed to play a key role in the development of Alzheimer’s.

Brunsveld enjoys the balance between academic research and targeted studies within a company setting. "Some scientists focus on work that’s so fundamental, it may never lead to a real-world application. That’s a bit too abstract for me," he says. "I need more context. I want to be able to picture where a concept might eventually be used. You never know if it’ll work out, of course - but having that possibility in sight is motivating. Students appreciate that too; it helps to have a bigger goal to work toward."

Several team members at the start-up once began as master’s students or PhD candidates in Brunsveld’s research group. He finds it deeply rewarding to help create jobs in this way. "I may not have become a reverend, but even in this role, I’m helping people grow," he says. "Most students already struggle with choosing a study path, let alone figuring out what they want to do after. Over the course of two years, you see them try things out, gain confidence, and really come into their own. At first, you’re mainly a teacher to them. But by the end, you hope to be more of a mentor, a sounding board."

Joining Brunsveld’s group means having the freedom to chart your course. "Of course, we’re all working within a shared theme - protein-protein interactions - but we don’t tell students exactly what to do," he explains. "At most, I give them a gentle nudge in the right direction." He grins and adds, "Sometimes, I must tap the brakes a little."

You can’t do everything, and you have to accept that. Otherwise, you’ll quickly hit your limits. Luc Brunsveld

For Brunsveld, if his students and PhD candidates are doing well, the group is doing well - and so is he. "Being able to contribute to their development is my biggest motivator. That’s what I do my research for. The process itself is so rewarding to see. Knowing that, in most cases, everything will work out gives a sense of peace. It’s satisfying to let them go once they’re ready."

Prioritizing Full professor at 33. The pressure might intimidate many, but Brunsveld sees it as a natural progression in his career. He’s content with life as a full professor. "Not every profession is meant for everyone, and that’s a good thing. For example, I could never be an administrator, a plasterer, or a journalist. It’s important to realize what you can or want to do, and what you don’t."

It’s crucial to recognize what you’re capable of, what you truly want, and what you’re not cut out for. Luc Brunsveld

He makes it sound easy, but it definitely isn’t. Brunsveld is a hard worker. "I learned that by working in my father’s bakery. Even when I got tired of making pastries, the work still had to be done. Because I was a quick learner, I could put in long hours. During my free time, I worked in the bakery, and on the train to university, I studied for my exams. That way, I could pay for my studies and finish them quickly."

Brunsveld learned to make the most of the time he had. "I still do that, even when it comes to relaxation."

But the professor admits: it’s a lot of balls to keep in the air. His secret? "I do a lot of things on the fly, and it works just fine. People have kids without taking a course first, so why not figure things out as you go? You have to make choices and set priorities. Knowing what you can let go of is an important skill. You can’t do everything, and you have to accept that. Otherwise, you’ll quickly hit your limits. I also enjoy helping others with that, so they can learn to let go a bit."

New subjects This year, Brunsveld turns fifty. He has no idea what his life will look like in five years - but that doesn’t scare him. It keeps things interesting. "Right now, we’re working on an exciting topic: protein condensates." Condensates are tiny droplets where proteins are packed tightly together. They form, for example, when cells in the body are under stress. "We’ve recreated these droplets in the lab and are now developing chemistry that allows us to manipulate them. In terms of applications, it could go in many directions, like drug development. I’m excited about it."

Kitchen chemistry Things are also changing at home now that two of Brunsveld’s three children have started university. "It’s beautiful to see this shift in life stage. As a family, we’re entering a new era."

When Brunsveld is at home, he’s truly present. "My family is my way of letting go of work. For example, I regularly go to the gym with my wife." He also enjoys spending time in the kitchen. He doesn’t use recipes. "I just see what’s in the fridge and work with that. You wouldn’t do that in the lab," he laughs. "I admit it, I’m a bit opportunistic. I get started without figuring everything out first. I just try. Sometimes things fail, but how bad is that really?"

About A Spark of Life

A Spark of Life is a series of stories from NEMO Kennislink. Without the ability of molecules to organize themselves, we wouldn’t exist. Scientists are working to replicate how molecules function. They study what drives molecules, but what drives them? We’re publishing the interviews Michelle Wijma conducted with TU/e scientists Patricia Dankers, Luc Brunsveld, and Ghislaine Vantomme.

TU/e PhD students work together on AI solutions in the Intensive Care Unit (ICU). They obtained their doctorate from the Department of Electrical Engineering on...

Research by TU/e, the Catharina Ziekenhuis, and Philips shows that the image quality of ultrasound improves with two ultrasound transducers. Vera van Hal...

Greater understanding of how depression progresses thanks to brain scan.