SPECIAL SEMINAR Amphitheater CLCC Eugène Marquis

Network-based approaches to study human context-specific cell signalling

Abstract

Our group aims to understand and describe the organisation principles of cell signalling that allow the diverse and context-specific cell responses and phenotypes. It is well established that signalling responses happen through complex networks. However, most signalling research still uses linear pathways as the ground truth. Moreover, signalling responses are highly dependent on context, such as tissue type, genetic background etc and therefore these static pathways are not always suitable. There is also a high bias in the literature towards kinases and pathways for which reagents and prior knowledge is readily available. This leaves a huge dark space in our understanding of cell signalling and significantly hinders studies of its general principles. In the first part of this talk I will present various network-based methods and approaches that we have developed in the group to extract active network signatures from omics datasets and to study condition-specific signalling networks and their relation to phenotype. For the second part I will present 2 ongoing projects to showcase the use of our tools to study fundamental biological questions. The first one focuses on the effect of different tissue contexts on signalling network rewiring downstream cancer driver gene mutations in cancer. The second one showcases the combination of executable modelling strategies with integrative omics and network analysis to gain insight into melanoma drug resistance mechanisms.