Transposable elements, or “jumping genes,” make up nearly half of our genome. Once dismissed as junk DNA, these mobile sequences—particularly retrotransposons—are now understood as powerful genomic forces that can copy and paste themselves across the genome, shaping evolution, development, and even disease.  

Yet, despite their significance, scientists had never actually seen one of these elements at high-resolution in action inside a living cell – until now. In a recent breakthrough, scientists at IMBA and the MPI of Biochemistry Martinsried used cryo-electron tomography to capture the first structural snapshot of a retrotransposon particle navigating the cellular landscape. 

The work, published in Cell, was spearheaded by Sven Klumpe, now group leader jointly at IMBA and IMP and at the time member of the Plitzko lab, and performed in collaboration with Julius Brennecke’s lab at IMBA. Their findings shed new light on how these ancient elements move and function within their host cells. 

But just as remarkable as the discovery is the story behind it. What began with an informal seminar invitation evolved into a tight and interdisciplinary collaboration. In this interview, Julius Brennecke and Sven Klumpe reflect on how their paths crossed, how their complementary expertise combined to spark something unexpected, and why they believe people and curiosity are key drivers of exciting discoveries. 

A talk that sparked a discovery 

It all began with a seminar invitation. Nothing out of the ordinary at the Vienna BioCenter , where ideas and people flow freely between institutes. Structural biologist Sven Klumpe, then member of the CryoEM technology group at the Max Planck Institute of Biochemistry in Martinsried, Germany, was invited by GMI Group Leader Silvia Ramundo to give a seminar about his work on cryo-electron tomography (cryo-ET). 

“During my PhD, I developed new tools for cryo-ET, using Drosophila tissues as a model,” Klumpe recalls. “One day, I saw virus-like particles inside the nuclei of ovarian cells, right near the nuclear pore. At the time, I wasn’t completely sure what I was looking at—at first, I thought that my flies had a viral infection - until I learned about retrotransposons”. 

Interested in Klumpe’s work, Julius Brennecke, Senior Group Leader at IMBA, was attending the seminar. Thanks to his previous work on the PIWI pathway, he confirmed that those “viral particles” may not be viruses at all but could indeed be retrotransposons. 

“Kirsten Senti in my group had recently strayed off the beaten path of our host-centric view on studying retrotransposons,” Brennecke explains. “He was exploring how retrotransposons adapted their expression patterns in fly ovaries, and when I saw Sven’s striking images, we recognized the strength that our orthogonal approaches could have to understand these jumping genes.”  

The right retrotransposon at the right time 

It turned out that Klumpe had captured something no one had imaged before: an active retrotransposon in a wildtype Drosophila ovary. “Under normal conditions, transposons are tightly repressed by the cell’s genome surveillance systems,” Brennecke explains. “To study retrotransposon activity, we usually have to knock out the host’s defense system. But then all transposons turn on at once, and it becomes like a retrotransposon zoo. Studying a single one becomes nearly impossible.” 

But, in science, there are always exceptions. Serendipitously, Klumpe had stumbled upon a special retrotransposon, Copia, which – for reasons yet unknown – evades silencing and is naturally expressed in wildtype flies, allowing the scientists to catch it in the act.  

“This gave us a clean system to study one transposon in action without needing to dismantle the fly’s defense system,” Klumpe explains. “With my imaging approach and Kirsten’s fly genetics, we could track what was happening in an actual tissue, not just a petri dish. That’s powerful.” 

The collaboration between Klumpe and Brennecke took off. Their combined expertise provided invaluable new insights into retrotransposon biology and yielded the first structural snapshot of a retrotransposon in action. “We were amazed by the response from the scientific community,” Brennecke comments. “Everyone was super excited by this finding, its implications and the potential this technology holds.” 

The power – and pain – of cryoET 

At the heart of this success was cryo-ET, the cutting-edge imaging technology Klumpe helped advance. “Cryo-ET allows scientists to visualize cells and tissues in their native state, at nanometric resolution,” Klumpe explains. The technique uses focused ion beam scanning electron microscopes – most commonly used in the semiconductor industry – to cut ultrathin slices of frozen biological samples. 

However, this process isn’t always smooth. “When I started working on cryo-lift-out, a technique to prepare tissue samples for cryo-ET, it was painstaking,” Klumpe recalls. “I spent many long-hour sessions at the microscope, failing repeatedly and having all the problems you can imagine. For years, nothing worked.”  

Fortunately, persistence paid off. Klumpe helped develop critical improvements to make this technology viable for various biological applications. “We’re now at the point where we can train people to master in just a few weeks to months what before used to take years,” Klumpe says. This leap made the team’s retrotransposon project possible—they could finally look inside real tissues and directly observe the capsid structure of the Copia retrotransposon. 

A campus that connects people 

Beyond its scientific merit, this project highlights the impact of strong collaboration, a pillar of IMBA’s and the Vienna BioCenter’s scientific culture. “The campus’ atmosphere of curiosity and openness is key,” Klumpe comments. “I came here to give a talk and suddenly found myself having deep scientific conversations with people from a variety of fields. That doesn’t happen everywhere.”  

“To me, this is a case study of what happens when you put the right people in the right place and give them space,” Brennecke points out. “The collaboration wasn’t planned, it happed simply because people were curious—and Silvia Ramundo, who's a great connector, brought us together.” 

Klumpe and Brennecke’s joint discovery is also a testament to hard work and resilience in the pursuit of knowledge. “It’s the people like Sven that push science forward,” says Brennecke. “He’s not just highly skilled—he has that “hobby cellar” mentality that technology development often needs. You have to be persistent, almost obsessed, and willing to fail for years until you eventually succeed.”  

Building a new future together 

Sven Klumpe recently returned to the Vienna BioCenter—this time as a joint group leader between IMBA and IMP. This innovative double affiliation will help him establish cryo-ET at the Vienna BioCenter, providing new research opportunities in retrotransposon biology and beyond. “This position came independently of my collaboration with Julius,” Klumpe explains. “But a lot of what I learned about the campus during that process – about cross-disciplinary thinking and the kind of ideas that can emerge here – is what convinced me this is the right place to build my group.”  

Klumpe’s arrival adds another dimension to IMBA’s and the Vienna BioCenter’s interdisciplinary landscape, essential to making major discoveries. Brennecke has no doubt that his is the way forward: “Programs like the new interdisciplinary postdoc fellowship – where fellows work across two labs with complementary expertise – are essential to attract people who can bridge fields and bring fresh ideas to the campus.” 

Looking ahead, the two scientists already envision many future collaborations “I’m especially interested in exploring the structural cell biology of transposable elements, which only becomes tractable due to recent technical developments,” Klumpe says. “Transposons offer a rich playground, especially with tools like cryo-ET. I think there’s a lot more to discover."  

“And again, it will always come down to people,” Brennecke adds. “Techniques don’t make discoveries—people do. If we continue to create an environment where bold ideas are welcome and supported, I’m sure the next big breakthrough is just around the corner.”