Université de Strasbourg

Fluorescent rhodopsin

Towards the engineering of a fluorescent rhodopsin

USIAS Fellow : Massimo Olivucci

Rhodopsin proteins in vertebrates, invertebrates and unicellular organisms are amazing demonstrations that light can be exploited by relatively basic molecular machines to carry out vision, ion-pumping, ion-gating and even gene-expression regulation. Such diverse functions are made possible through variations in the environment surrounding the same molecular antenna suggesting that the re-engineering of natural rhodopsins provide a versatile, yet largely unexploited, tool for modern technology. Indeed, a new rhodopsin-based technique, optogenetics, is revolutionizing the field of neurosciences by allowing a beam of light to fire single neurons at precise spatial locations and times. In this context, highly fluorescent rhodopsins, which could be employed as voltage sensors to reveal the firing and transmission of the neural impulses, are eagerly needed. Regrettably, such tools have not been achieved yet. With the present project, we plan to leverage the flexibility of state-of-the-art quantum chemistry to construct, systematically, computer models of rhodopsins capable of simulating their color variability, light response and native fluorescence. Building and studying these models will unveil the mechanisms modulating the relaxation and equilibration of the protein fluorescent state at an atomic level resolution which, in turn, should reveal how to control them by suitable protein sequence mutations. It is hoped that, by integrating these research activities with those present at the Institut de Physique et Chemie du Matériaux de Strasbourg and exploiting the computer facilities at the Mésocentre of the University of Strasbourg, it will be possible to reengineer an eubacterial rhodopsin into an unprecedented optogenetic tool for action potential sensing and visualization.