It is an unusually grey, wet and foggy day in San Diego. On this April day Michelle Frei, who has been a postdoc at the University of California San Diego since October 2021, is reminded of November in Switzerland "except that it is not as cold". In a zoom call, she tells us how, as a high-school student with a focus on biology and chemistry, she examined insects during a hot summer in Wettingen, Switzerland. She notes with a laugh that these little creatures were not really that exciting. "But we were able to paddle about in the river while the others were forced to swot in the classroom. That was cool."
This episode is characteristic for this 31-year-old. "I'm very pragmatic, and my approach was always to do something for as long as I enjoyed it." The high-school student was interested in natural sciences. "I was fascinated by how things functioned at a molecular lever," she says. "I wanted to know what happened in a body if somebody had cancer or another illness." Studying chemistry was the obvious choice, but Michelle Frei wanted to study medicine or pharmacy first. "Then again, I thought I'd have to memorise too much for this." The Chemistry Olympiad gave her an opportunity to meet chemistry students who convinced her that chemistry was the best choice. And this proved to be right.
"On the way to chemical biology stardom"
After the native of Aargau completed her master's studies at the Swiss Federal Institute of Technology (ETH) in Zurich, she was certain that she wanted to continue with research. After a period in the private sector with Actelion, she commenced her doctorate with Professor Kai Johnsson at the Swiss Federal Institute of Technology in Lausanne (EPFL). His group specialises in the production of fluorescent molecules used in microscopy. "This enables the observation of biological phenomena in cells," explains Frei. Red, blue or green dyes are the classic choice used for this purpose. Light is shot at the appropriate molecules. These then emit another light back with a certain time delay. This delay, the so-called lifetime, differs depending on the dye involved. "This has been known for some time, but the knowledge had not been put to any practical use until now," she says.
In her dissertation, which has now been awarded the Prix Schläfli, she worked with dyes that bind a protein called HaloTag. She produced three variants of this protein. All three variants can be bound by the same dye, they then all have the same colour, but the previously mentioned lifetime is not the same. "This means that I can investigate three different things with a single dye," explains the chemist. "I can send one protein into the nucleus, another to the membrane and the third to the mitochondria." This procedure is called multiplexing. It represents a pioneering development for fluorescence microscopy that is used in applications such as biomedicine. Michelle Freis' doctoral supervisor Kai Johnsson is impressed. "I am convinced that this work will facilitate the use of fluorescence lifetime multiplexing considerably throughout the scientific community." He is under no doubt that "Michelle Frei is on the way to chemical biology stardom." This compliment initially rendered the young woman speechless. "Wow, a compliment like this coming from him is really an enormous honour."
Infatuated with research
She would love to return to Switzerland and head her own lab, but she wants to use the next year to learn even more in one of the most renowned laboratories in the world. "I've got a crush on research," she beams. "Understanding molecular processes is still fascinating to me." Her second greatest fascination is to be found in books, particularly Nordic crime thrillers. Should the Californian weather fail to live up to its sunny reputation in the future, the Swiss (women)can safely lose herself in Scandinavian winter – while taking in the view of the fog over San Diego Bay.