Chemical labeling method provides new approach for recording cellular activities

In living cells, a large number of temporal events occur simultaneously, each of them important for a given cell to perform its function. A faithful recording of these transient activities is a prerequisite for a molecular understanding of life, yet such recordings are extremely difficult to obtain.

Scientists at the Max Planck Institute for Medical Research in Heidelberg and their collaboration partners have developed a new technology that allows cellular events to be recorded through chemical labeling. Fluorescent color For subsequent analysis, opening entirely new ways to study cellular physiology. New method I am now published. science.

Recording of transient cellular events plays a crucial role in probing and understanding biological processes, yet it presents significant technical challenges. An ideal recording method would simultaneously observe large populations of cells, work in test tubes and in live animals, and allow recorded observations to be retrieved and analyzed later. Until now, methods meeting these criteria have been largely lacking: a gap that new technology can now fill.

“Our technology is based on a recorder protein that is irreversibly labeled with a fluorescent dye when an event of interest occurs in its vicinity,” says Magnus Karsten Huppertz, MPI’s Department for Medical Research. Describes a postdoctoral researcher in chemical biology. “This enables scientists to study very large numbers of cells in parallel ̶ in vivo or in vitro.”

Differentiated substrates record successive periods of activity.

The team, led by Kai Johnson and Julien Hablot, designed proteins that become labeled when a specific cellular activity and a fluorescent substrate are simultaneously present. Washing-in and washing-out of the substrate determine the duration of the recording, while cellular activity determines the degree of labeling. Moreover, by using differential substrates, different phases within an activity period can be recorded.

In his study, he created recorders for three different processes of central interest: receptor activation, protein-protein interactions and changes in calcium ion (Ca²⁺) to concentrate. The latter was employed to study the heterogeneity of Ca.²⁺ Alterations in cellular networks derived from glioblastoma, an aggressive brain tumor.

In close collaboration with the groups of Lisa Fink and Herrog Baer at the Max Planck Institute for Biological Intelligence in Martinsried, the authors successfully recorded patterns of neuronal activity in flies and zebrafish.

“Finally, we have developed a versatile recording platform for the parallel analysis of multiple simultaneous transients. Cellular events in vitro and in vivo,” concluded Jonas Wilhelm, a postdoctoral researcher in the same department.

The main challenge the scientists faced during their work was to optimize the newly developed recorder platform to ensure its robustness and efficient performance in a range of biological model systems. To explore the use of this new technology in different situations, they set up a number of comprehensive experimental arrangements.

“We are excited to provide new molecular tools that have the potential to enable new types of experiments and accelerate research in diverse fields such as neurobiology and oncology,” say Magnus-Carsten Huppertz and Jonas Wilhelm. “We were fortunate to be able to collaborate with scientists from different disciplines to make this new technology possible.”

In addition to the Max Planck Institute for Biological Intelligence, scientists from the German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), Heidelberg University, Genelia Research Campus, Virginia, US, and École Polytechnique Fédérale de Lausanne. EPFL), Switzerland contributed to this work.