Paola Picotti (born 1977) is an Italian biochemist who is Professor for Molecular Systems Biology at ETH Zürich.[1][2] She is Deputy Head of the Institute for Molecular Systems Biology. Her research investigates how the conformational changes of proteins impact molecular networks with cells. She received numerous awarded awards, among which the 2019 EMBO Gold Medal.[3]
Early life and education
Picotti grew up in Udine. Her mother was a mathematics teacher and her father worked in an electronics company.[4] Picotti studied medicinal chemistry at the University of Padua, and graduated in 2001.[5] She then moved into biotechnology, working alongside Angelo Fontana for her doctoral research. She joined the laboratory of Ruedi Aebersold as a postdoctoral fellow in the Institute for Molecular Systems Biology at ETH Zürich, where she developed approaches for the targeted analysis of proteins based on mass spectrometry.[5] She was appointed a scientific advisor at Aebersold's spin-out company Biognosys.[6]
Research and career
In 2011, Picotti was appointed to the faculty at ETH Zürich, first as an assistant professor at the Institute of Biochemistry and subsequently as an associate and full professor at the Institute of Molecular Systems Biology. She works in the field of mass spectrometry-based proteomics, the large-scale analysis of thousands of proteins from cells and tissues. Whilst proteomics offers the potential for wide-reaching analysis, detail on the structures or shapes of proteins is lost in the process.[6]
Picotti developed an approach that solves this problem, since it enables the analysis of the structures of thousands of proteins simultaneously. It combines limited proteolysis and mass spectrometry (so-called "LiP-MS" method), to generate a proteolytic pattern (akin to a barcode) that reports on the structure of every measurable protein in a sample. Comparison of structural barcodes from different biological specimens (e.g. samples from healthy individuals and from individuals with a disease) detects which proteins have altered structures in those specimens.[6][7]
Picotti has shown that this technique can be used to identify a new class of candidate biomarkers of disease (structural biomarkers), unravel basic principles of thermosensitivity of proteins and provide a new and often more sensitive way to detect altered biological processes. Also, since binding of a small moleculelocally affects the structure of a protein, the approach can be used to identify targets of small molecules and drugs, binding mechanisms and binding sites, thus rendering LiP-MS a valuable tool in drug development. Picotti uses LiP-MS to study protein aggregation in neurodegenerative disease, with a focus on Parkinson’s disease.[8]
Leuenberger, Pascal; Ganscha, Stefan; Kahraman, Abdullah; Cappelletti, Valentina; Boersema, Paul J; von Mering, Christian; Claassen, Manfred; Picotti, Paola (2017-02-24). "Cell-wide analysis of protein thermal unfolding reveals determinants of thermostability". Science. 355 (2637). doi:10.1126/science.aai7825. PMID28232526.
Piazza, Ilaria; Kochanowski, Karl; Cappelletti, Valentina; Fuhrer, Tobias; Noor, Elad; Sauer, Uwe; Picotti, Paola (2018-01-11). "A Map of Protein-Metabolite Interactions Reveals Principles of Chemical Communication". Cell. 172 (1–2): 358-372.e23. doi:10.1016/j.cell.2017.12.006. PMID29307493.
Mackmull, Marie-Therese; Nagel, Luise; Sesterhenn, Fabian; Muntel, Jan; Grossbach, Jan; Stalder, Patrick; Bruderer, Roland; Reiter, Lukas; van de Berg, Wilma D. J.; de Souza, Natalie; Beyer, Andreas; Picotti, Paola (2022-10-12). "Global, in situ analysis of the structural proteome in individuals with Parkinson's disease to identify a new class of biomarker". Nature Structural & Molecular Biology. 29 (10): 978–989. doi:10.1038/s41594-022-00837-0. PMID36224378.
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