Research

Research Priorities: Proteomics, structural systems biology, protein aggregation, Parkinson’s disease, mass spectrometry

Paola Picotti is a biochemist. The Picotti laboratory studies how protein conformational changes impact cellular networks both in normal physiology and in disease. The lab develops new mass spectrometric methods to monitor changes in the structure and function of proteins on a proteome-wide scale in biological samples like cells or tissues. These methods are applied in particular to study the effects of protein aggregation in neurodegenerative disease, with a focus on Parkinson's disease.

The Picotti group has developed a structural proteomics technique, limited proteolysis coupled to mass spectrometry (LiP-MS), which monitors protein conformational changes across the entire detectable proteome, in directly from complex samples (Feng et al. Nat Biotechnology, 2014). The resulting dynamic 3D proteomes can be integrated into functional proteomics screens to provide far more informative snapshots of complex proteome dynamics than can be obtained from protein expression screens alone. These structural proteomics screens detect protein functional changes due to numerous molecular events (e.g. catalysis, allostery, protein-protein interactions, and protein aggregation) simultaneously and in situ with a resolution of single functional sites. A goal of the Picotti laboratory is to integrate such dynamic structural proteomics data with static, atomic-level structural data, as well as biochemical and systems-level knowledge, to provide new quantitative readouts for complex biological processes and for detecting pathological states.

The Picotti laboratory applies these newly developed proteomic approaches to the study of protein aggregation, with a focus on the amyloidogenic protein alpha-synuclein (a-Syn) involved in Parkinson’s disease. In this field, the group discovered molecular regulators of the toxicity of a-Syn, thereby revealing potential targets for the modulation of Parkinson’s. Using a structural proteomic approach, the Picotti group also recently identified the determinants of protein and proteome thermostability and generated a map of protein-metabolite interactions.

Career

• 2021 Guest Professorship, University of Cologne, Cologne, Germany
• since 2017 Associate (Tenured) Professor for Molecular Systems Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule Zürich (ETH), Zurich, Switzerland
• 2011-2017 Assistant Professor for Protein Network Biology, Institute of Biochemistry, ETH, Zurich, Switzerland
• 2011 Group Leader, Institute of Biochemistry, ETH, Zurich, Switzerland
• 2007-2010 Post-doctoral Fellow, Institute of Molecular Systems Biology, ETH, Zurich, Switzerland
• 2006 Post-doctoral Fellow, MATI Excellence Centre, University of Udine, Udine, Italy
• 2002 Research Fellow, CRIBI Biotechnology Centre, University of Padua, Padua, Italy

Functions

• 2018 Member, Strategy Committee, Department of Biology, ETH Zurich, Zurich, Switzerland
• 2018 Member, Steering Committee, Functional Genomics Center Zurich (FGCZ), Zurich, Switzerland
• 2017 Jury member, Mass Spectrometry in Life Sciences Award, German Association for Mass Spectrometry (DGMS), Germany
• 2016 Member, Advisory Board, Broad Institute, LINCS Center, Harvard Medical School (HMS), Harvard University, Cambridge, USA
• 2015 Member, Research Committee, Parkinson’s Schweiz, Switzerland
• 2014 Chair, Working group, Protein Aggregation Diseases, Human Proteome Project (HPP), Human Proteome Organization (HUPO), Houston, USA
• 2014 Scientific advisor, Biognosys AG, Schlieren, Switzerland
• 2013 Member, Executive Committee, Proteomics section, Life Sciences Switzerland (LS2), Switzerland
• 2013 Member, Hiring Committees for professorial positions, ETH, Zurich, Switzerland
• 2010 Member, Editorial Board, Journal of Proteomics

Projects

• 2020-2024 Member, AntiResist (29 groups), Swiss National Science Foundation (SNSF), Switzerland
• 2019-2024 Coordinator, Consolidator Grant “Three-dimensional dynamic views of proteomes as a novel readout for physiological and pathological alterations”, European Research Council (ERC)
• 2019-2022 Member, European Proteomics Infrastructure Consortium providing access (EPIC-XS), Horizon 2020, European Union
• 2018-2022 Sinergia Grant “CRSII5”, Swiss National Science Foundation (SNSF), Switzerland
• 2018-2021 Coordinator, Technology Translation, Strategic Focus Area Personalized Health and Related Technologies (SFA-PHRT), ETH Domain, Zurich, Switzerland
• 2014-2019 Coordinator, Starting Grant “Unraveling the cellular responses to aberrantly-folded and aggregated proteins”, ERC

Honours and Memberships

• since 2022 Member, European Molecular Biology Organization (EMBO)
• 2021 Discovery in Proteomics Award, Human Proteome Organization (HUPO)
• 2021 Winner, Life Sciences Falling Walls Competition, Falling Walls Foundation, Berlin, Germany
• since 2020 Member, German National Academy of Sciences Leopoldina, Germany
• 2020 Rössler Prize, ETH Zurich, Zurich, Switzerland
• 2019 Gold Medal, EMBO
• 2018 Juan Pablo Albar Protein Pioneer Award, European Proteomics Association (EuPA)
• 2018 Friedrich Miescher Award, Life Sciences Switzerland, Switzerland
• 2016 Robert J. Cotter Award, American Human Proteome Organization, USA
• 2016 Award for outstanding independent research in the field of mass spectrometry, Swiss Group for Mass Spectometry (SGMS), Switzerland
• 2016 Young Investigator Award, EMBO
• 2014 “Top 40 under 40” Power List, The Analytical Scientist
• 2012 Latsis Prize, ETH, Zurich, Switzerland
• 2011 Research Professorship, Swiss National Foundation (SNF), Switzerland