Prof. Fred Nyberg
Fred Nyberg on the importance of sample quality in peptide research
Professor Nyberg´s prominent research focuses on peptidergic mechanisms in chronic pain and drug addiction. He also studies neuroendocrine effects on cognition, an area he has been involved in since his graduate years, when studying prolactin’s effects on the brain. After receiving his PhD, Professor Nyberg was awarded a grant to conduct a research project on endorphins, supported by the National Institute of Drug Abuse, and his research focus shifted to include addiction. He was soon appointed professor in Pharmacology at Uppsala University (1988-1992). Since 1993 he is Professor in Biological Research on Drug Addiction at the Department of Pharmaceutical Biosciences Uppsala University. Professor Nyberg has contributed profoundly to the research community, with over 450 articles in his list of publications.
Difficulties with peptide detection
Early on in his career, professor Nyberg came in contact with peptides and found an interest in their role in different pathophysiological mechanisms. It was well-known at the time that peptidergic systems could be stressed, and due to quick degradation of the peptides, there were no means to analyze the short lived molecules. Depending on the methods used, they had to focus on peptides of high abundance to get reliable results, “because of this we probably missed significant differences in patient materials” professor Nyberg states. Professor Nyberg is convinced that the sample preparation steps and having control over the post mortem time is crucial when analyzing peptides; “when there are methods to preserve peptides in your samples, as with the Stabilizor T1, it is axiomatic to use it in your peptide studies” he says. “With the methods that were available then we could see a lot, but today with better techniques and preservation methods such as the Stabilizor T1, we can see a lot more”.
Implementing heat stabilization
Professor Nyberg was one of the pioneer users of the Denator technology, and published an article using the Stabilizor T1 technology already in 2009. In that study, heat stabilization was used to quantitate peptides derived from the peptide precursors proenkephalin, prodynorphin and preprotachykinin following Naloxone-precipitated morphine withdrawal in rats. The peptides were analyzed with a mass spectrometry-based approach and the study was an attempt to improve biomarker detection. In this context stabilization is absolutely crucial, as it enables extraction in water based buffers, making them compatible to LC-MS analysis.
Today the Stabilizor T1 is fully integrated into professor Nyberg’s research; he uses heat stabilization to ensure sample quality from sampling throughout the entire research process, including dissection at room temperature, to achieve successful analysis of low abundant peptides and quickly degrading phosphorylations.
Areas that professor Nyberg believes also would benefit from improved peptide workflow are in the search for new molecular entities and biomarkers. “Today there are few good biomarkers, which makes it difficult to study how different signaling systems are affected by drugs. As there are no biomarkers available, it is difficult to understand the side effects from adjacent sub-signaling systems”.
“With the new possibilities to standardize and secure sample preservation, novel possibilities open up for studying peptidergic events” professor Nyberg concludes.