New Proteomics Technique Gives Insight into Cellular Stress

In order to study how specific stress signals influence protein synthesis, a team of scientists developed a new proteomics procedure. The trick is this: when measuring all the proteins in the mass spectrometer, a booster channel is added to specifically enhance the signal of newly synthesized proteins to enable their measurement. Thus, acute changes in protein synthesis can now be tracked by state-of-the-art quantitative mass spectrometry. The results were published yesterday in Molecular Cell.

“Since the amount of newly produced proteins within a brief time interval is rather small, the challenge was to record minute changes of very small percentages for each individual protein,” says senior author Christian Münch of Goethe University.

The newly developed analysis method provided the team with detailed insight into the molecular events that ensure survival of stressed cells. The cellular response to stress plays an important role in the pathogenesis of many human diseases, including cancer and neurodegenerative disorders. An understanding of the underlying molecular processes opens the door for the development of new therapeutic strategies.

“The method we developed enables highly precise time-resolved measurements. We can now analyze acute cellular stress responses, i.e., those taking place within minutes. In addition, our method requires little material and is extremely cost-efficient,” Münch explains. “This helps us to quantify thousands of proteins simultaneously in defined time spans after a specific stress treatment.”

Due to the small amount of material required, measurements can also be carried out in patient tissue samples, facilitating collaborations with clinicians. The team demonstrated for the first time that two of the most important cellular signaling pathways, which are triggered by completely different stress stimuli, ultimately result in the same effects on protein synthesis.