Exploring molecules in motion

By Luhnyae Campbell

In honor of October being Energy Awareness Month, we are featuring Petra Fromme, director of the Biodesign Institute Center for Applied Structural Discovery, and her work aimed to create an artificial leaf which produces green energy.  

From the intricacies of biology to uncharted quantum territories, researchers in the Biodesign Center for Applied Structural Discovery are accelerating discovery with groundbreaking technologies and methods.

The center is led by director Petra Fromme, a Regents Professor of biochemistry with the School of Molecular Sciences at Arizona State University. She is a world leader in creating technologies for investigating protein structure. Fromme and her team pioneered a technique called serial femtosecond crystallography, which allows researchers to study proteins in nature-like conditions and capture the first movies of biomolecules at work.

Below, Fromme talks about the center’s successes and challenges, the enormous contributions of students, and why ASU is a place where “mission impossible” ideas become reality. Answers are edited for length and clarity. 

Question: What is the research focus of your center?

Answer: The Biodesign Center for Applied Structural Discovery brings together researchers from diverse disciplines to unravel the dynamics, structure and functions of biomolecules.

To study the ultrafast dynamics of biological systems and materials at atomic detail, we are building the world’s first compact X-ray free electron laser. CXFEL will allow us to image these dynamics with ultrashort X-ray pulses that can unravel the movement of molecules, atoms and electrons.

These movies of molecules “in action” have exciting implications for discovery of new drugs as well as novel quantum states that enable new materials for energy conversion.

Q: Why is this work important to society?

A: Our faculty’s work will lead to innovations that ultimately can improve human health, provide clean energy and food for future generations, and create new materials with potential uses in biomedicine, architecture and space exploration, along with unlimited applications in industries such as semiconductors.

We aim to also provide training for students at all educational levels, as well as to germinate a new cadre of K-12 educators to communicate across disciplines in an effort to solve a wide range of societal problems from health to clean energy.

Q: What is the biggest challenge in this field of research?

A: Currently, most of the information we have on biological systems and materials only provides a static picture. But the function of these systems is highly dynamic. Unraveling the dynamics of molecules and materials is a very challenging goal that requires groundbreaking technology developments.

Time and funding are the biggest limiting factors with a group of faculty whose imagination is expansive and who are committed to creating new technology for a new era in structural discovery.   

Q: What is something you consider one of the center’s biggest successes?

A: We designed and built the first short-pulsed accelerator, the compact X-ray light source (CXLS), with funding from ASU and generous private donors, Leo and Annette Beus. Based on this developmental achievement, we were awarded our first NSF funding for the design of the second accelerator, the CXFEL. In February 2023, we showed the proof-of-concept with the first X-rays from the CXLS. This was the basis for a new, $90 million NSF award in for the construction of the CXFEL.

The faculty of the center were key to this success. It is a point of tremendous pride to me as the center director to see our assistant and associate professors advance along the tenure track process, obtain their first significant funding (including DOE and NSF CAREER awards), and contribute their unique expertise to promising collaborations.

Q: How are students involved in the center’s research?

A: Students are recruited across the education spectrum (i.e., high school, undergraduate and graduate programs), and are involved at all levels, from small teams to large multi-institutional research endeavors.

Our first compact accelerator, the CXLS, was built with the help of 30 undergraduate and five graduate students. Many of the students are veterans and come from very diverse backgrounds. They form a critical creative workforce and are committed to advancing discovery in our center.

Q: If someone gave your center $100 million, what would you do with it?

A: Donations of this size could transform our research program, allowing us to fund technology development as well as pilot projects for experimental ideas. We could also develop the next generation of even more powerful compact accelerator technology to study biomolecules inside cells and quantum materials and solve problems in medicine and energy conversion.

Q: How does your research align with Biodesign’s mission of nature-inspired research?

A: In our center, we aim to unravel the secrets of nature to develop novel solutions to the emerging problems in our society. Understanding how nature converts sunlight into chemical energy will allow us to build systems that are as efficient as nature. We are also developing bio-inspired catalysts and materials for carbon capture and hydrogen production.

Our material research in the field of quantum physics is also inspired by nature, where processes like quantum coherence and quantum coupling, as well as transition from ordered to disordered states, have been used by nature to enable light capture, energy conversion and electron transfer.

Q: What key events set you on your research path?

A: The new research direction of BioXFEL was driven by the goal to move X-ray crystallography from static pictures to movies of molecules at work. With John Spence and the team at ASU and our international collaborators, in 2009 we conducted the first serial femtosecond crystallography (SFX) experiments at the free electron laser at Stanford, pioneering a new era in structural biology. Access to the only five free electron lasers in the world was limiting, which led me to engage in the quest to build the world’s first compact free electron lasers at ASU.

Q: What is your favorite thing about working at Biodesign?

A: My favorite thing working at Biodesign is the unique and very interdisciplinary research environment. We work with scientists in different centers on new solutions for challenges ranging from sustainability and the environment all the way to the molecular basis of diseases, with the goal of finding new treatments. There is no better place in the world than ASU to work together on the unexplored paths to make new discoveries that could change the world. At Biodesign, we can make mission-impossible ideas become reality. The CXFEL project is a prime example, which moved from being a dream to becoming reality because of exceptionally strong support from the Biodesign Institute and ASU leadership.   

Q: Has your teaching and mentorship helped inform your research, and if so, in what ways?

A: Engaged, highly motivated students at the undergraduate and graduate level are the core of the success of our center. Students bring new ideas and projects to the center, like the PhD student Karie Behm (now working at the CDC), who started the Lyme disease project.

We also began a collaborative project with Mayo Clinic to study a protein tied to nonalcoholic fatty liver disease because my graduate student Michael Morin contacted a clinician on his own initiative and worked weekly with children at the Phoenix Children's Hospital who suffer from early onset of this liver disease.