Uppsala University launching new method to visualize DNA strand breaks

(Image removed) Erik Bivehed and Johan Heldin, The Faculty of Pharmacy

All potential drugs are subject to numerous different trials before approval, not least with a focus on possible impact on our genetic material. The sooner possible DNA damage is detected, the faster an unfavorable candidate can be dismissed. The need for resource-efficient analysis tools is palpable, and now researchers at Uppsala University are introducing a method that paves the way for more detailed data than previously possible.

“We are launching a method that, in addition to detecting DNA strand breaks, distinguishes between single-strand and double-strand breaks and also estimates the occurrence of each type. Our method is an improvement on previously available tools and will generate new and important information in both preclinical and clinical drug research, as double-strand DNA breaks provide considerably more serious challenges than single-strand breaks,” says Erik Bivehed, Postdoc at the Department of Pharmaceutical Biosciences.

(Image removed) The new tool is a further development of Comet assay, a method created in Uppsala in the 1970s. After being sophisticated in laboratories around the world, Sweden and Uppsala University regained pole position, and in 2021 Professor Björn Hellman's research group in Toxicology introduced both Flash-comet and a statistical method to analyse comet data: Results that continue to arouse great enthusiasm and expectations are palpable for the new opportunities that are currently opening up.

“The method that we present in scientific journal Nucleic Acids Research offers a practical and time-saving tool to identify DNA strand breaks in one single operation. That it also scans a larger part of the cell means that we can now detect DNA damage that has to date been basically impossible to detect with Comet assay. Overall, we hope that our work will contribute to fewer mistakes and a more efficient path to imporoved drug treatments,” says Johan Heldin, Researcher at the Department of Pharmaceutical Biosciences.

(Image removed) Erik Bivehed in the lab

The new method is developed in an interdisciplinary collaboration between Ola Söderberg's and Björn Hellman's research groups at the Faculty of Pharmacy, Bo Stenerlöw's research group at the Faculty of Medicine, SciLifeLab's bioinformatics platform NBIS and the Uppsala University Hospital. The next step is already in the works in the form of applications for the new tool, where Johan Heldin plans to study induced DNA breaks with the goal of increasing our understanding of how and why they occur.

“We are also in talks with the Uppsala University Hospital's Laboratory for testing of cancer drugs resistance about the possibilities to initiate a collaboration on double-strand DNA breaks in the early stages of tumor growth, a work we hope will add important knowledge about how tumor cells react to cancer drugs and what causes resistance to cytostatics and similar treatments, says Erik Bivehed.

READ ARTICLE

• Visualizing DNA single- and double-strand breaks in the Flash comet assay by DNA polymerase-assisted end-labelling (Bivehed E, Hellman B, Wenson L, Stenerlöw B, Söderberg O, Heldin J., Nucleic Acids Res. 2024)

LEARN MORE

• Research in Pharmaceutical cellbiology (Söderberg, Heldin)
• Research in Genetic Toxicology (Hellman, Bivehed)
• Innovation award to Ola Söderberg and Björn Hellman for Sloppymerase

CONTACT

(Image removed) Erik Bivehed, Postdoc
Dep. of Pharmaceutical Biosciences
Erik.Bivehed@uu.se

(Image removed) Johan Heldin, Researcher
Dep. of Pharmaceutical Biosciences
Johan.Heldin@uu.se

Text: Magnus Alsne, photo: Mikael Wallerstedt, Magnus Alsne a o