PROSPECTS · PROteomics SPECification in Time and Space

Proteomics is a major new field in biomedical research, which deals with the large-scale identification and characterization of large groups of proteins, or “proteomes”. These can either be the components of a subcellular organelle or compartment, or even the entire protein complement of whole cells and tissues. Proteomics is essential in the functional annotation of the genome and in future attempts to build a quantitative, ‘systems-based’ description of cell biology. However, current ‘first generation’ proteomics approaches largely measure protein complexes and proteomes as homogeneous and static entities with little or no quantitative annotation. PROSPECTS (PROteomics SPECification in Time and Space) is a proposal by world leaders in this young discipline to make a major advance, both by developing much more powerful instrumentation and by applying novel proteomics methods that will allow us to annotate quantitatively the human proteome with respect to protein localization and dynamics. Complementary technologies, including mass spectrometry, cyro-electron microscopy and cell imaging will be applied in innovative ways to capture transient protein complexes and the spatial and temporal dimensions of entire proteomes. We will develop these new proteomics technologies in a generic fashion to maximize their utility to the wider biomedical community and we will generate comprehensive data sets that will foster many downstream functional studies. Our approaches will also generate unique insights into the molecular basis of multiple forms of human disease, specifically neurodegeneration and other diseases related to folding stress. The multidimensional data sets generated in PROSPECTS will be integrated using advanced data aggregation and machine learning, made available to the scientific community via annotated online public databases and used as a basis for a systems biological modelling of the human proteome, with spatial and temporal resolution within the cell.