Quantitative real time analysis of the ERK pathway during embryogenesis – Cell-Whisper

Successful embryogenesis requires the differentiation of the correct cell types, in defined numbers and in appropriate positions. In most cases, decisions taken by individual cells are instructed by signals emitted by their neighbours. A surprisingly small set of signalling pathways is used for this purpose. The FGF/Ras/ERK pathway is one of these and mutations in some of its individual components cause a class of human developmental syndromes, the RASopathies. Our current knowledge of this pathway is, however, mostly static. We lack an integrated understanding of its spatio-temporal dynamics and we can imperfectly explain its highly non-linear (switch-like) response to a graded increase in input stimulus.

This systems biology project combines advanced quantitative live imaging, pharmacological/optogenetics perturbations and computational modelling to address, in an original animal model organism, 3 major unanswered questions, each corresponding to a specific aim of the proposal:

? Aim 1: What is the spatio-temporal dynamic of intracellular signal transduction in response to FGF during embryogenesis?
? Aim 2: How is the switch-like response to graded extracellular signals controlled at the molecular level?
? Aim 3: Can the results be integrated into a predictive computational model of the pathway?

Through this approach, in a simple model organism, we hope to gain an integrated molecular understanding of the spatio-temporal dynamics of this pathway and of its robustness to parameter variations.