Charting colorectal cancer Interactomes at structural resolution using chemical crosslinking and mass spectrometry

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Large numbers of cancer mutations have been exposed through genomics; however, it remains unclear how most cancer genes function and exert influence on disease processes. Here we propose to develop a quantitative approach to map protein interactions on global scale at high throughput using cross-linking mass spectrometry (XL-MS). The method will be used to chart the native protein interaction landscapes across cancer cell lines, generating structural information on protein topology and protein-protein interaction (PPI) surfaces. A deeper understanding of how somatic mutations affect protein structure, function and rewiring of cellular networks, will provide mechanistic insights and underpins new intervention strategies.