Quantitative and systems analysis of RAS/MAPK signalling networks

A protein-network centric approach, where disease is considered as the consequence of perturbations of intracellular networks, has been very powerful for obtaining a comprehensive understanding of the molecular mechanisms underlying disease phenotypes. Consequently, in recent years, researchers have extensively mapped disease-relevant protein interaction networks and if we connect all interactions reported in the literature, a high level of cross-talk and complexity is observed. However, some interactions may not be physiologically relevant, or only relevant in certain cell types, tissues or in a specific context (stimuli, interaction partners). In my talk I will present examples of using 3D structural and quantitative data to understand how RAS/MAPK signalling networks are context-specific rewired. I will further present a protein engineering approach that enables the rewiring of networks in a designed fashion, which was used to probe the contributions of individual signalling branches to an output/ phenotype in physiologically-relevant colon cancer organoids.