The pioneer.

Ten years ago, when Hondele accepted a postdoctoral position at ETH Zürich, she was one of the first wave of researchers to examine these structures more closely. Since then, there is mounting evidence that numerous essential processes take place within these compartments. "At those early conferences, we could really sense an optimistic mood," she recalls. "There are still many major questions unanswered in this field of research."

At the moment, researchers cannot even agree on what to call the process by which these compartments are formed – is it a type of phase separation, as can be observed with oil droplets in water, or is it caused by transient interactions in which proteins briefly interact like schooling fish? It is an important question, but Hondele's focus lies elsewhere: "I'm more interested in the biological processes that underlie these phenomena. How exactly do these compartments form? What use might they have? What is happening in there?"

Lab instead of childhood dream

It was this curiosity that prompted her to abandon her childhood dream for a career in research. As a child growing up in the small Bavarian town of Freising, it was "crystal clear" to her from a young age that she wanted to become a doctor. "But soon after I started my medical degree, I found I was far more fascinated by the life sciences," she says. It was not enough for her to simply apply existing knowledge – she wanted to get to the bottom of things for herself. Soon after finishing her “Physikum” examination in medicine at the University of Regensburg, she changed her major to biochemistry. As a recipient of the prestigious Fulbright scholarship, she gained her first laboratory experience at the University of Massachusetts based in Worcester in the United States, and she enjoyed the work immensely.

But the real trial by fire for her newly chosen career path was her doctoral dissertation at the European Molecular Biology Laboratory (EMBL) in Heidelberg and Ludwig-Maximilians-Universität München. It was only toward the end of her PhD that the crystallization of a protein complex finally catalyzed a long-awaited breakthrough; she subsequently renewed her contract and proceeded to shed light on a structure in the cell's nucleus that had eluded many before her. "For an entire year, I was under immense pressure, and I did almost nothing else – the competition was intense," recalls Hondele. "I learned to tough it out in the lab." This experience – and the widely lauded publication it produced – provided the final impetus she needed to continue her scientific work.

Creativity comes while climbing

Like in her postdoc at the ETH, Hondele, who now heads her own working group, focuses on a particular class of enzymes frequently found in membraneless organelles, the so-called DEAD-box ATPases. Within the membraneless organelles, these enzymes are often found together with specific nucleic acids, for example messenger RNAs, which contain the blueprints for new components within the cell. The ATPases appear to play a key role, not only in RNA processing, but also in the formation and regulation of condensates and membraneless organelles. DEAD-box ATPases are present in all living beings, from bacteria to humans, but the precise functions of many of these enzymes – like that of the membraneless organelles themselves – remain a mystery.

That is their theory, at least. "Maybe the RNA is processed there. But the formation of the compartments might simply be a response to stress with no specific function. Or maybe surplus components are stored there," says Hondele. Membraneless organelles also appear to play a role in neurodegenerative diseases, such as ALS and Alzheimer's disease.

It is on her short trips to the mountains with her partner or friends – climbing in summer or skiing in winter – that Hondele finds the time to meditate on these kinds of questions. Does she have the same sense of ambition in the mountains as she does in her research? She takes a moment to consider the question. Not really. Sure, she has summitted a 6000-meter peak in Kyrgyzstan, but normally, while she is hanging from the face of an enormous cliff, her main ambition is to clear her mind. "Often, you have a whole day just to think. And sooner or later, along comes an idea about how it all might fit together."