User case: SciLifeLab essential for FOI’s research on investigating radiation-induced damage

The Swedish Defence Research Agency (sv: Totalförsvarets forskningsinstitut, FOI) conducts research to support national security and defense, including developing tools to detect and protect against chemical, biological, radiological, and nuclear threats. Ionizing radiation damages cells and tissue, which can lead to chronic diseases such as cancer and fibrosis. In order to obtain a better understanding of this process, FOI turned to the Swedish Metabolomics Centre (SMC), a unit at SciLifeLab, for help.

“We observed that when cells are exposed to radiation, although they may not die, they are altered and begin to release different substances into the cell culture media around them, which we call ‘conditioned media’,” says Pernilla Lindén, researcher at FOI’s Department for Chemical Agents.

When unirradiated cells were exposed to this ‘conditioned media’, they began showing symptoms of radiation damage, despite never being directly exposed to radiation. “This suggests that something is being secreted from the irradiated cells, something that can cause serious systemic effects in the body, but can also be used as a potential marker of radiation exposure” Lindén explains.

At FOI they have the ability to measure targeted metabolites — known molecules they can detect and quantify — but lacks the advanced tools to detect and identify large sets of metabolites. Lindén reached out to Annika Johansson, Head of Unit at the Swedish Metabolomics Centre, SMC, in Umeå.

At SMC, metabolomics is performed using advanced mass spectrometry — a technology that allows researchers to detect metabolites in biological samples. Unlike targeted methods, untargeted metabolomics can identify and quantify a vast range of metabolites, including those not initially anticipated. “At SMC, they’re experts at finding what you don’t even know you’re looking for,” says Lindén.

Finding the invisible

Together, their teams designed the experimental setup to find what the irradiated cells secreted into their environment.

“The challenge with metabolomics is that it’s not a method that measures everything. It’s not like CSI — you don’t just put a sample in and get a clear answer about unknown compounds,” says Annika Johansson. With metabolomics, there is lot of manual work involved, and the researchers need to make sure that they are not overwhelming the user with data.

“The key is to understand what really matters. Our goal is always to deliver insights that move the research forward. In this case, we wanted to help FOI understand what was happening in the cells and the surrounding media,” says Johansson. To get the most value out of the data, the teams went back and forth with preparing the test and reference samples whilst planning the experiments in detail.

The experiment was successful, and whilst the exact compounds responsible for the effects are still being investigated, the results revealed biological pathways consistent with radiation response — promising clues for future studies.

“The long-term goal would be a non-invasive method to quickly determine whether a person has been harmed by radiation or chemical agents”

The collaboration has now expanded to develop ways to identify airborne tracers of exposure to radiation and chemical agents such as toxic industrial chemicals and nerve gases. This time, SMC helped analyze metabolites that can be detected in both plasma and breath samples — again aiming to detect early biochemical signals of exposure.

“The long-term goal would be a non-invasive method to quickly determine whether a person has been harmed by radiation or chemical agents, and what kind of medical care they might need,” says Lindén.

Critical to the project’s success was SMC’s vast in-house library of known metabolites and lipids, its specialized software for interpreting complex data, and the hands-on training FOI’s team received on how to analyze the raw data themselves. “We also needed Annika’s help to select what samples to include in the analysis in order to be able to answer the questions we had,” says Lindén.

From first contact to completed analysis, the project took only a few months, which Johansson attributes to the strong communication and clear experimental design. “It’s exciting to see how access to the right infrastructure and expertise can help with such an important purpose,” Johansson concludes.

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