During his education, Högbom encountered certain chemical reactions in nature that were virtually impossible to perform in the lab. This sparked admiration for nature’s ability to always find new paths to achieve results. He has now found ways to use advanced X-ray techniques and computational power to learn how certain chemistry is possible.

“This is truly curiosity-driven basic research. We’re trying to understand these reactions by mapping them at the atomic level,” says Högbom.

Building DNA

At the heart of his research lies a protein – ribonucleotide reductase (RNR). This protein produces the building blocks of our DNA. In doing so, it uses metal ions and radicals – highly reactive atoms or molecules.

The metal is needed to initiate the chemical reaction. A chemical reaction often occurs in multiple steps, each requiring activation energy – like a push – that can come from heat, light or a catalyst. In some reactions, electrons move to continue the process. Metal ions can drive this by creating an imbalance in electrical charge. But there is a risk that this imbalance will affect much more than the desired reaction.

“For the protein to succeed, every atom must be controlled and directed to react properly. Lab experiments often result in chaos and entirely different reactions,” says Högbom.

He is using X-ray free-electron laser technology to understand how this occurs in nature. The technology allows him to observe the motion of atoms during chemical reactions. It is currently available at only a few locations worldwide, so Högbom’s research team is collaborating with fellow researchers at Berkeley and Stanford.

“Access to these facilities is very limited, so we only conduct actual experiments a few times a year. They are so advanced that they resemble research projects all of their own and require a great deal of preparation,” he says.

The energy in a pulse from a free-electron laser causes the protein sample to explode. The energy density in a pulse is as high as if all sunlight hitting Earth were concentrated on an area the size of a pinhead. But before the sample explodes, scientists can create images of atomic motion.

“So far, we have captured certain parts of the process in still images. Our next step is to capture enough images in sequence to create a film of the entire reaction. This will enable us to see how the protein controls the process.”

Eliminating bacteria

Although this is basic research, there are several potential applications. The RNR protein variant that Högbom is studying is found in e.g. Mycoplasma, which can cause respiratory infections, as well as in certain Staphylococcus strains responsible for a number of infections.

“When we understand how the chemical reaction works, we and others can develop methods to influence it. Our research could become the first step toward new therapies.”

I am constantly amazed by nature's solutions. If there is any way at all of starting a chemical reaction, nature has already discovered it.

There are other potential applications, such as in efforts to slow global warming. The research team has been working with a protein that uses iron ions to convert methane into methanol. Methane is a potent greenhouse gas released during natural processes and oil drilling but is difficult to capture. Converting methane into methanol would allow it to be recycled.

“We have reached an exciting stage, but a number of control experiments lie ahead to confirm and replicate our results.”

All experiments are followed up with calculations requiring access to highly powerful computing environments.

“Advances in computational technology in recent years are one reason we can succeed in our research. They enable us to analyze and verify our results.”

He also stresses that long-term financial support is essential for basic research:

“The Scholar grant gives me confidence as well as freedom, making groundbreaking research possible. For me, this funding has been absolutely crucial,” Högbom says.

AI not quite there yet

AI has been used with great success in a number of research fields, such as prediction of protein structures, which was awarded the Nobel Prize in Chemistry in 2024. But it is not yet able to predict how protein chemistry is performed

“Hopefully, we will see new AI solutions that we can both contribute to and benefit from. But the data is currently insufficient to train an AI model. First, we need to conduct experiments to show how chemical reactions actually occur in proteins.”

He is driven by a desire to truly understand how certain chemistry is possible – curiosity that also finds other outlets in everyday life.

“Whenever something breaks in the lab, I feel a strong urge to take it apart to see what happened. At home, I have several projects in varying stages of repair,” he says.

Text Magnus Trogen Pahlén
Translation Maxwell Arding
Photo Magnus Bergström