Professor Paola Picotti

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.