The Department of Biotechnology, Chemistry and Pharmacy (DBCF) has been granted the "Department of Excellence 2018-2022" award from MIUR, worth 7'000'000 euros. The funded research project entitled "Development and application of a technology platform based on QM/MM simulations for the design of light-responsive molecules" has its origin in the Laboratory for Computational Photochemistry and Photobiology (a bi-national lab operating at Bowling Green State University and at the University of Siena) where the innovative ARM (Automatic Rhodopsin Modeling) computational technology has been developed. The aim of the project is to extend ARM capabilities beyond the study of wild type rhodopsins, implementing the accurate modeling of rhodopsin mimics and mutants in a high throughput fashion. The ability to engineer rhodopsins with modulated photoactivity and the synergy with the other expertise of the DBCF (biochemistry, medicinal chemistry, organic synthesis) will allow for their application in the field of optogenetics and photopharmacology as well as solar energy conversion and synthetic biology.
The first application delivered by the technology platform will be a combined optopharmacology and optogenetics approach to improve and restore visual functions in retinal diseases. Indeed, rhodopsin is a membrane receptor belonging to the superfamily of G-protein coupled receptor (GPCR) that is responsible for photoreception in the vertebrate retina. Aberrant expression of rhodopsin is linked to Retinitis Pigmentosa (RP), a group of retinal diseases that provokes defects in the visual function up to blindness. These may include optopharmacology tools, namely small molecules able to restore rhodopsin function and signaling acting through multiple mechanisms, as well as optogenetics strategies to target wild-type and modified opsin genes to surviving retinal cells through suitable delivery models.
To accomplish such goals new human resources will be enrolled and trained for the project and new facilities will be set-up at DBCF: the High Performance Computing Centre, the Mass Spectroscopy centre and the High Throughput Screening lab.