The Nobel Prize in Physiology or Medicine

Research Lecture at Nobel Forum

Research Lecture at Nobel Forum

Date: March 12, 2020, 16.00

Speaker: Matthias Mann
Director of the Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Munich

Venue: Nobel Forum, Nobels Väg 1, Karolinska Institutet
Host: Professor Juleen Zierath,, Department of Molecular Medicine and Surgery, Karolinska Institutet

Title: Mass spectrometry based proteomics: single cell sensitivity, deep learning and clinical applications

Mass spectrometry-based proteomics is now being employed in a wide variety of applications spanning the entire breadth of molecular biology. Great instrumental advances continue to be made and I will discuss a few of these, including advances in algorithms and bioinformatics and focusing on the new tims-TOF technology, which now allows ultra-sensitive analysis of only a few or single cells.

These and other experimental advances are applied in our group in cell signaling. Novel phospho-proteomics technology now enables studying complex signaling events in vivo. We have used this to uncover the long sought substrates of the Parkinson’s disease kinase LRRK2. Subsequently, we have developed a target engagement test that can now support clinical trials. In circadian rhythms, phosphoproteomics has revealed that a large percentage of the phospho-proteomics is coordinately regulated during the day and night cycle, including at synapses in the brain. We have also used this technology to unravel signaling events downstream of opioid receptors in the brain in the context of analgesia and addiction.

Body fluids like plasma have long been of great interest to researchers in proteomics because of their potential to directly ‘phenotype’ individuals with minimally invasive procedures. However, the high dynamic range – along with other challenges – have so far stymied this promise. The ‘plasma proteome profiling’ approach developed by our group now allows us to study the plasma proteome rapidly in a wide range of conditions. Finally, I will summarize our efforts in cancer proteomics, especially in finding new markers in chemorefractory disease by proteomics and how we can now use single cell cancer proteomics from FFPE tissue to directly determine the molecular correlates of cellular heterogeneity in this disease.