A New Lens on Biology

Biotechnology

A New Lens on Biology

• June 13, 2025

Fabian Voigt, Ph.D., is a global leader in the development of microscopy technology that addresses new problems in biology.

A postdoctoral researcher in neurobiology at Harvard University, Voigt has been a Visiting Scientist several times at MDI Bio Lab, where he designed and helped to install the Lab's mesoSPIM microscopy system, a powerful, groundbreaking technology for imaging whole organs and organisms at multiple magnifications and in three dimensions.

Now he is pursuing new ways to observe brain activity that's related to real-time positional awareness - creating microscopes that can track neurons firing in zebrafish (a favorite research model at the Lab) as they swim and interact with other zebrafish.

He presented his latest work at last week's Stanley G. Schultz Seminar, and we caught up with him afterwards (transcript condensed and edited for clarity):

Q: Do you recall your first time looking through a microscope?
Fabian: My parents gifted me a microscope for Christmas when I was 10 or 11 years old. That was one of those kind of kits with both some samples to look at and ways to grow your own brine shrimp… that was probably the beginning of it all.

Q: Were you more interested in the technology or the samples?
Fabian: Back then, it was just about looking at anything I could get my hands on. I struggled a bit with the microscope itself… I took it apart and then couldn't put it back together again. It took me quite a while.

Q: In your career, is it the microscope or biological problems that drive your work?
Fabian: I initially wanted to become an astronomer, to build telescopes. It helped that I grew up next to an old observatory. Then I started my undergraduate work, and I kind of fell in love with biology… I think this was the progression: from being excited by the instrument itself, to developing an instrument for biological questions, towards asking more biological questions myself.

Q: What was the goal with the mesoSPIM, your 3D whole-organ imager?
Fabian: A colleague was struggling with a commercial microscope. Software was crashing, alignment was difficult. I thought, 'hey, we could come up with something that's a little better.' We developed this tool, but then we also made it available on an open-source basis… not just giving scientists access but empowering them to change it to suit their particular questions.

Q: Have people taken it into new areas you hadn't expected?
Fabian: Oh yes. My colleague Nikita Vladimirov is collaborating with particle physicists on a completely non-biological issue - to hunt for evidence of dark matter, the fundamental forces that hold the universe together. This microscope was meant to look at very large transparent samples and then spot little fluorescent particles in tissues… but they see it can be applied to an astrophysics problem. Nobody predicted that. You need environments where people from different disciplines can interact.

Q: You recently invented a new type of lens for viewing tiny samples in liquid media - you were inspired by the principles of mirror-based telescopes, such as the Hubble, but also by the way the retinas of scallops are arranged. Where did that idea come from?
Fabian: You can take a telescope, invert it and use it as a microscope. There are some overlooked properties of mirrors… for instance that you can immerse it in liquid and still get a sharp image. So I was reading a book about animal eyes, and the scallop eye is a mirror-based eye… reflective, filled with liquid… looks a little like a tiny telescope: Nature figured it out!

Q: What specific biological questions are you pursuing now?
Fabian: I'm fascinated by the sense of space and how a brain is able to take in information from all kinds of senses and then create a unified representation of where the animal is in space - a representation an animal will use to inform its next behavior, maybe it's hunting, maybe socializing, maybe mating.

We've never been able to draw a detailed circuit diagram of how spatial information flows through a living brain. We know of cells that represent location in a mouse brain, but we are missing a lot of details on how these activity patterns comes about. And the sense of space is so central to all our daily lives. I think that knowing more about it is absolutely crucial for moving forward with human health. For instance, if you think about neurodegenerative diseases, one of the things that you lose is to be able to find and track things, a sense of orientation in space.

Q: Will this new approach to microscopy allow you to see exactly which brain parts light up while animals behave?
Fabian: Yes. The idea is to see the brain of a moving zebrafish, the whole brain, in 3D as the fish explores its environment. We use fluorescent indicators to turn neuronal firing into brightness changes that are visible with a tracking microscope.

Q: You have traveled all over the world, helping scientists build new microscopes, and your own academic career has taken you from Germany to Switzerland to the U.S. Any observations about differences among these institutions?
Fabian: What I love about science in the U.S. in general is it has a very low hierarchy - that's a huge strength. In Europe there are boundaries between people at different levels of their career. At MDI Bio Lab, for instance, it's easy to interact across career levels… Like with my chalk talk (Schultz Seminar) yesterday: It was a fun experience, informal, the weather was beautiful and there were a lot of trainees there.

MDI Bio Lab is small but powerful-everyone knows everyone, it's easy to just walk across campus and make new connections. It has excellent infrastructure, an imaging facility with instrumentation you won't even find at bigger institutions. Coming here over the last three years, it's great to see how the Lab is rapidly evolving, a lot of growth, and all the new initiatives. It's a small institution with a lot of punch.