Spatiotemporal modeling of signaling pathways: impact of endosomal compartmentalization and application to gonadotropin receptors.

Summary

This thesis project aims to develop new dynamic models to describe the compartmentalization of signaling pathways. Using hybrid formalisms developed in the probabilistic and computational communities, as well as single-cell kinetic signaling and fluorescence imaging data, we will investigate the role of receptor trafficking in endosomal vesicles in the cellular response to extra-cellular stimulation.

We will seek to understand possible stationary states and the variability and/or robustness induced by compartmentalization. We will then develop simulation and parameter inference algorithms for characterizing receptor pharmacology. This methodology will be applied to gonadotropin receptors, in a context of developing non-hormonal strategies for reproductive control.

This project is being carried out within the MUSCA interdisciplinary team, comprising biologists, mathematicians and computer scientists, and will take advantage of "crossing" approaches between discrete and continuous or hybrid models.

Following on from the exploratory project IMAGO (2022-2024), this thesis aims to pursue the development of new formalisms to describe the spatio-temporal dynamics of cell signalling.

Contact :

• Chloé Weckel
• Linkedin