Systems biology of proteins classically uses a technique called proteomics, which measures thousands of proteins in a biological system at once. This is very powerful, but it does not look at the structures (i.e. shapes) of these proteins, but only at their amounts. However, protein structures are critically important to understand how proteins function in health or mis-function in disease. In this project, the Picotti lab has addressed this problem by developing an approach to study the structure and function of thousands of proteins at the same time, within their native biological context. The group applied these methods to study protein aggregation (a type of protein structural change), in particular in diseases that are linked to aggregation such as the neurodegenerative Parkinson’s disease (PD). The overall goal of the project was to study protein aggregates or assemblies in healthy physiology and in disease and their modulating factors, develop new approaches to the discovery of disease biomarkers and extend the functional and mechanistic knowledge obtainable from systems biology. The approach provided the community with new methods for global analyses of proteins in cells and tissues, allowed the discovery of a new type of disease biomarkers for neurodegenerative and other diseases and shed light on regulators and mechanisms of protein aggregation.