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Spatial control of cell signaling with optogenetics

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Optogenetics are recently developed tools, based on photosensitive proteins, that enables the use of light to activate or inhibit specific proteins and control intracellular processes. One key benefit of optogenetics is the capability to induce signalling perturbations that are localized in space and time, while classical genetic and pharmacologic approaches can only create permanent and global perturbations. Optogenetics is a particularly interesting tool for studying the spatio-temporal processes involved in cell signalling which governs cell behaviour during e.g. migration or division.

In this project, we use the optogenetic system Cry2/CIBN : upon blue light absorption, Cry2 associates with CIBN which is anchored at the cell membrane (see figure). By fusing Cry2 with signalling proteins, it would be possible to activate specific cell signalling pathways.
The aim of this project is to study the spatial resolution of the molecular response to light irradiation. To this avail, a home-built microscope setup combines a Digital Micromirrors Device (DMD), to perform spatially resolved light stimulation, with imaging in total internal reflection (TIRF) configuration, to detect and quantify Cry2 recruitment on the basal membrane. The DMD will make it possible to create different stimulation patterns and the consequences in terms of molecular recruitment will be imaged in TIRF. Based on these results, it would be possible to optimize the illumination conditions to improve the spatial resolution of light-induced effects and study cell response as a function of the spatial pattern of signalling proteins.
The proposed work would include optimizing the optical setup and the instruments control interface and measurements in live cells. It will take place in an interdisciplinary team with people specialized in physics, optics and biology. The prospective student will team up with a PhD student who is already working on this project.

Contact :

Irène Wang – tél. 04 76 51 47 29 – irene.wang@univ-grenoble-alpes.fr

Antoine Delon – tél. 04 76 63 58 01– antoine.delon@univ-grenoble-alpes.fr

Optogenetics