December 1, 2022
Editor's note: This is the first installment of a five-part series profiling the researchers who work on ASU's compact X-ray free electron laser. Read the other installments: Q&As with CXFEL Labs Chief Scientist William Graves, CXFEL Labs Director Robert Kaindl and Assistant Professor Sam Teitelbaum and CXFEL Chief Engineer Mark Holl.
When Petra Fromme was a master’s student in chemistry, she attended her first scientific conference. In a session led by Paul D. Boyer, a renowned chemist who later won a Nobel Prize, she realized her own research contradicted what he was presenting.
“My supervisor kind of kicked me in the side and said, ‘Petra, you should stand up and raise your hand,’” she recalls. “I was really reluctant. I knew that he was the leading scientist in the field — a real big shot — and he was explaining his model, and I had contradicting results. But finally, I raised my hand a tiny little bit.”
Instead of dismissing her comments, Boyer asked to see Fromme’s research poster after the session. By that time, the lights had been turned out in the poster hall. Undaunted, Boyer borrowed a flashlight from one of the security guards so he could see Fromme’s work.
“He made such a big impact on my career, because someone this high up in the academic chain was taking my work seriously. He was a big impact on me deciding on a scientific career and becoming a professor,” says Fromme.
Today, Fromme is a “big shot” scientist herself. Her research team pioneered the use of X-ray free-electron lasers (XFELs) to make movies of biological molecules in action. Now, she is helping to build the world’s first compact XFEL (CXFEL) at Arizona State University, where she is director of the Biodesign Center for Applied Structural Discovery and a Regents Professor in the School of Molecular Sciences. Like Boyer did for her, she seeks to inspire and encourage the students she mentors.
In this Q&A, Fromme talks about her own career path, how the CXFEL project came to be and what excites her about its future.
Question: How did the CXFEL project originate?
Answer: My colleagues and I have worked since 2003 on the idea to use XFELs to get movies of molecules at work. Then we did exciting groundbreaking experiments, but experimental time at the XFEL was very limited at this time as there was only one XFEL in the world. Eventually, this increased to five, but this only increases the number of experiments you can conduct in the world at the same time from one to five. The idea was born in 2014 to team up with a group at MIT to build a compact XFEL here at ASU.
I had a meeting with the chair of physics, chair of chemistry, chair of engineering. We came up with the idea for the Center for Applied Structural Discovery and the idea to build the CXFEL here. I presented this to President Crow in a meeting and he said, “Let’s do it.”
Q: What expertise are you known for?
A: What I was most known for in my early career was my work in photosynthesis — how plants convert light into chemical energy. My group was the first in the world to isolate these huge green complexes that capture light, crystallize them and solve their very first structures.
I always thought that would be my biggest accomplishment. But as soon as I came here in 2002, I was approached by (ASU Regents Professor of physics) John Spence about the idea of making movies of molecular processes using XFELs. We submitted 10 grant proposals, but they were all rejected because the referees deemed it a “mission impossible.” In 2009, we conducted the first X-ray diffraction experiments at the world’s first XFEL at Stanford and showed it was possible. Upon resubmission, with the first experimental results included, we got a perfect score.
Since then we have published more than 40 papers in high-impact journals. I think now I’m best known for this pioneering work on time-resolved studies at XFELs.
I think my final major accomplishment might be bringing the compact XFEL technology to the lab.
Q: What has been the biggest challenge in the CXFEL project and how have you and the team overcome it?
A: The major challenge was funding. Let’s face it: It was clear from the beginning this would be the first instrument of its kind in the world. When we tried to get funding from federal agencies, we were told that we had to first show the proof of concept. But when the first instrument will cost $15–20 million, how will you show the proof of concept? It’s a catch 22 — you need the money to build one, but you have to show that it will work before you get the money. That was a major challenge.
Without President Crow’s huge commitment to the Biodesign C building and initial funding of $9 million, we would never have gotten the program off the ground. And then, on a plane, I met Leo Beus without knowing who he was. We talked about teaching and then the CXFEL project. He was very interested, and we exchanged cell phone numbers. He visited ASU and the CXFEL labs multiple times, and then he and his wife made a $10 million donation. He was like a white knight.
Q: Why is ASU the right place to build this instrument?
A: First, we have the expertise and motivation. We pioneered the use of XFELs in biology, which has a huge impact on the future. ASU is the scientific lead on the NSF-funded BioXFEL Science and Technology Center, where scientists from 10 institutions work on developing novel biological techniques using XFELs.
Traditional structural biology methods use X-rays to produce static pictures of the structure of molecules. However, biomolecules are very dynamic when they work. Having just a static picture is like having a picture of a horse standing. You don’t know how it is able to run.
The idea of getting movies of molecules at work was one of the major driving forces after the Linear Coherent Light Source opened at Stanford in 2009. It was the first hard XFEL in the world, and we did the first time resolved serial crystallography experiments. I think our very first experiment is still one of the most cited papers from XFELs.
The scientific community wanted to have more access to XFELs. And we at ASU are one of the leading teams in the world in the field, including Bill Graves, an expert on the accelerator physics needed to build a compact XFEL. We teamed up with MIT, where they had been developing compact accelerator technology for over 20 years. Combining MIT’s expertise on the technology with our strong expertise on using the technology for its applications was unique.
Second, which is probably even more important, we have ASU President Crow and his team, leadership that believes in making mission impossible — like building a compact XFEL — possible. To have a leader at the university who is willing to take that risk and make investments to build an instrument that doesn’t exist anywhere in the world — I think ASU is the right place, and very likely the only place, where such an endeavor could have been attempted.
Q: What was a pivotal moment in your career that led you to where you are today?
A: I think one of the real big moments in my career was when ASU tried to attract me to the U.S. I had a non-tenured assistant professorship in Germany. I was in the process of working toward tenure when I met Tom Moore, an ASU photosynthesis researcher, at a conference in San Francisco. He asked if I had ever considered coming to the U.S., and I said no. I had two kids and a family in Germany. He said, “How about you just come and give a seminar?”
He invited me in November, which was a very clever idea. The chair of chemistry took me for two hikes in the Superstition Mountains. Coming from West Berlin, it was so amazing. In Berlin, I was surrounded by a wall for the first 28 years of my life — you could never drive longer than 20 minutes and you were at the wall. And now to look to the horizon and there’s no street, no house, just this beautiful landscape. I considered moving to the U.S. for the first time because the faculty in the department welcomed me with open arms and I fell in love with the landscape of Arizona.
After I came here, I saw the huge impact that the innovative spirit of ASU had on my research. I am a very optimistic person, and I like to work on projects that are high risk, high impact. Here at ASU, my innovative spirit was fully appreciated, and my colleagues and I work on highly collaborative projects with big goals that other people may deem impossible.
Q: How do your personal interests enhance your professional endeavors?
A: I have to admit something. I nearly didn’t become a scientist. I was very interested in science in high school, but I was also very interested in music and considered a career as a musician or musical instrument builder. Finally, I decided to study biochemistry with the goal to cure cancer and keep music as a hobby. I have played viola since I was 9, and I have always played in orchestras. Currently I play viola in the Tempe Symphony Orchestra, the Scottsdale Philharmonic and a string quartet.
Many people wonder: “How could you do that with all the work at the center and the CXFEL?” But I tell you I can do it only because I have this hobby. When I am at an orchestra rehearsal, I have to focus 100% on the music. When you start thinking about the nasty comments from the referee on your last paper, or how to get your grant resubmitted, then you will play badly. You have to completely focus on your music. And this clears the brain from any unproductive thoughts. After rehearsal, my brain is completely clean, and I have a new, unbiased view on the challenges I face. My best creative ideas always come after these rehearsals.
Other people do other things, like sports or painting or cooking. But something that’s independent from the scientific work gives you a fresh perspective and a clear view to enable completely new ideas.
Q: What motivates and excites you most about your work?
A: I’m most excited doing experiments and making discoveries together with my students. This often happens at the XFELs. Beam time is so valuable that as the professor, I have to be there with my students so that we can make decisions together on the fly. We often spend one or two weeks together with our national and international collaborators at the experiments.
This kind of teamwork with my students is when the most exciting new discoveries are made. I’m really a hands-on person, and I love to work with my students and to do new things. The more risky, the better. Furthermore, making the discoveries, showing them to the public, discussing them at conferences, and exchanging information and ideas with colleagues is one of the most exciting aspects of our work.
Q: What potential application or aspect of the CXLS/CXFEL is most exciting to you?
A: My real motivation is still the holy grail of photosynthesis, which has not been solved. How do plants split water into oxygen, protons and electrons using visible light and earth abundant metals? When we discover how plants do that, then we could build systems which are as efficient as nature and as stable as man-made systems.
The other main motivation is developing molecular movies of the dynamics of medically relevant proteins. For example, it will be extremely exciting to make a movie of how a virus binds to a cell and then visualize all the processes that allow the virus to enter the cell. Another example would be to see how a cancer cell hides from destruction by the immune system. There are many applications on diseases where we could study the dynamics and structure of the molecular cause of diseases at the atomic level.
Q: Who has had the biggest impact/influence on your career?
A: I want to name two people. One was Paul Boyer. The second person was John Spence. He was such an influential person, sparking with ideas all the time. He could not sit still when he had a new idea, he had to jump up and draw a scheme on the whiteboard.
John was always open to ideas, even if they were outside of his research field. When we started working together, he was not really interested in photosynthesis at first. But one day he knocked on my door frantically and said, “Petra, we have to talk. You have to explain photosynthesis to me. I gave a talk at Berkeley and a collaborator there asked me about it. But I have no time, so please explain it to me in just five minutes.” I started to explain, and after about two and a half hours, he still wanted to learn more. He told me it was so fascinating and exciting, and he had never realized that it is all about physics.
I always looked forward to our Friday brainstorming meetings. We worked so well together as we were both very spontaneous, innovative and creative. And while we often had very heated discussions on new ideas, we always treasured the experience of the productive scientific dispute. So over the last 20 years of my career, John really had a huge influence on me.
Q: How do you envision your career in the future?
A: I am looking forward to the first light of the compact X-ray light source and our endeavor to develop and build the CXFEL. It will give the next huge push to our research. Currently, work on the big XFELs is always limited. We have the chance to conduct one or two, maybe three experiments per year, and we have to travel all over the world to do them. We can make such huge impact on getting these molecular movies of biomolecules or unraveling the dynamics of quantum materials when we have the compact accelerators here at ASU.
Compact XFELs have the potential not only to enhance research at ASU. When we build the first prototypes here and make discoveries that no one even imagined five years ago, other institutions will want to have one of these instruments, custom designed for their needs. Then maybe in 10 years, there are five or 10 compact XFELs at different universities and research institutions in the U.S. Hopefully, having initiated this research, our group at ASU will play a role in advancing these technologies and the discoveries that can be made with them even further.
Biodesign Institute and its CXFEL Labs are partially supported by Arizona’s Technology and Research Initiative Fund. TRIF investment has enabled hands-on training for tens of thousands of students across Arizona’s universities, thousands of scientific discoveries and patented technologies, and hundreds of new startup companies. Publicly supported through voter approval, TRIF is an essential resource for growing Arizona’s economy and providing opportunities for Arizona residents to work, learn and thrive.