Light Induced Cell Organization and Polarity – LICOP

The cell architecture and dynamics are controlled by a complex molecular circuitry able to process information from environmental cues in order to drive the cell into functional states accordingly. For instance, cells get polarized as they migrate or divide. To do so, they have to amplify local and transient signals into stable and system-level asymmetries. This process primarily relies on two interconnected networks of proteins, namely effectors and regulators, rather than transcriptional regulation. Effectors are assembled in transient macromolecular complexes that orchestrate the spatial architecture of the cell and its dynamics. Regulators interpret physical and chemical cues to control the effectors structures in time and space through biochemical modifications. An important issue is the subcellular regionalization of these protein networks. It appears that a given cellular state can be viewed as an arrangement of spatially and temporally restricted functional modules. These modules are subcellular autonomous entities specified by their composition of effectors and their signaling program of regulators. Such a modular organization of the cell implies that a given regulator can be simultaneously involved in distinct functions at different places in the cell. Thus, one given molecular actor is not responsible for one function. Rather, a function is imprinted in the advanced computational tasks - such as amplification, adaptation, filtering, integration, and decision-making - done by a group of molecules acting collectively in a specific local context. Despite its essential role in the signal processing underlying the cellular response and functions, the tight spatiotemporal coordination of regulators activities and effectors structures in a given module remains poorly understood.

In this context, we propose to develop a systemic approach applied to the cell polarization in a well-documented biological model: a migrating fibroblast. We will make use of optogenetic techniques to trigger biochemical modifications with a spatial and temporal resolution not accessible with the conventional molecular and pharmacological toolkit. By combining these optogenetic tools to induce localized signaling perturbations with live cell imaging of the cell response and mathematical modeling, our goal is to dissect the signal processing done by the network of regulators and address the following fundamental questions:

1) How is signal processing coupled to the local architecture of the cell?
2) What is the information support that drives the transitions between subcellular modules and cellular states?
3) How are the cell sensitivity and robustness with regards to local perturbations conditioned by the cellular environment?

Our ultimate goal is thus to establish an integrated and quantitative framework of the signal processing that translates information contained in molecular events into system-level functions.