Welcome to the Picotti Lab at ETH!

Our 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.

LiP-MS

We 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 (Cappelletti et al. Cell, 2021).

We applied LiP-MS to the study of protein aggregation and discovered molecular regulators of the toxicity of the amyloidogenic protein alpha-synuclein, involved in Parkinson’s disease. We also identified the determinants of protein and proteome thermostability and generated a map of protein-metabolite interactions.

Data Exploration and Analysis

Protti	MSstatsLiP
The goal of protti is to provide flexible functions and workflows for proteomics quality control and data analysis, within a single, user-friendly package. It can be used for label-free DDA, DIA and SRM data generated with search tools and software such as Spectronaut, MaxQuant, Proteome Discoverer and Skyline. Both limited proteolysis mass spectrometry (LiP-MS) and regular bottom-up proteomics experiments can be analysed.	Tools for LiP peptide and protein significance analysis. Provides functions for summarization, estimation of LiP peptide abundance, and detection of protein abundance and structural changes across conditions. Utilizes functionality across the MSstats family of packages.