Text: Yvonne Vahlensieck
Curiosity is the driving force in Maria Hondele's life. In her research, the biochemist is exploring new frontiers in the field of cell biology.
In Maria Hondele's office on the fourteenth floor of the Biozentrum, a wall calendar competes with the view over Basel and the river Rhine. The calendar depicts a lonely Norwegian fjord. This Scandinavian country has long exerted a certain magnetism for the assistant professor. She has just returned from her summer vacation there, where she had a chance to rest and recharge.
Hondele conducts a whirlwind tour of her laboratory facilities and offices. She has made considerable strides since her career led her to Basel in early 2020. "I got off to a quick start in spite of the pandemic," she says. In record time, she assembled a team consisting of a laboratory manager, a postdoctoral researcher and six doctoral students. And she managed to add a 1.5-million-euro starting grant from the European Research Council to the one-million-Swiss-franc research grant her project had already received from the Swiss National Science Foundation.
New revelations about old-established structures
These prestigious grants are a testament to the contribution of Hondele's work in an area of science that is paving the way for the future. She gives an enthusiastic account of her field, a relatively new research area that is continuing to gain momentum. The structures she is investigating are microscopic compartments inside of cells known as biomolecular condensates and membraneless organelles.
Unlike other structures, such as the mitochondria – the "powerhouses of the cell" – these compartments are not separated from the interior of the cell by a membrane. Instead, several individual components come together as if by magic and then disperse again on their own. For a long time, science was not overly interested in this phenomenon; many viewed these compartments as artifacts with no particular function.
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."
Maria Hondele was born in 1981 and studied pre-clinical medicine and biochemistry at the University of Regensburg. After earning her doctorate at the European Molecular Biology Laboratory (EMBL) in Heidelberg and LMU München, she spent six years as a postdoctoral researcher at ETH Zürich. Since September 2020, she has been Assistant Professor of Biochemistry at the Biozentrum of the University of Basel.