讲座摘要

This talk details the progressive development and application of optoproteomics, an innovative technique derived from optogenetics, by our research group initially established at École Normale Supérieure, later moving through Sorbonne University the laboratory of Computational and Quantitative Biology, and currently situated at INSERM U1195 (Neuronal Diseases and Hormones) since 2019. Optoproteomics leverages light-sensitive noncanonical amino acids (ncAAs) to modulate protein functions with high temporal and spatial precision, presenting a significant advancement over traditional small molecule-based controls reliant on molecular diffusion. We have employed three distinct types of ncAAs: caged-ncAAs which reveal a photolabile side chain under light, photo-cross-linking ncAAs that bond with adjacent molecules upon illumination, and photo-switchable ncAAs that undergo reversible conformational changes with varying light wavelengths. The application of these technologies has been particularly successful in manipulating membrane proteins such as NMDA receptors, tyrosine kinase receptors (TrkA), and LAT3 amino acid transporters, achieving unprecedented control over protein activity and interaction. The first two types of receptors are key therapetutic targets for neurodegenerative diseases such as the Alzheimer's. LAT3 is an emerging target for safe chemotherapy. Our research demonstrates the utility of optoproteomics in enhancing understanding of cellular signaling dynamics, particularly through site-specific modifications and real-time tracking of protein interactions. This work not only extends the capabilities of optogenetics but also opens new avenues for studying and manipulating biological systems at the molecular level.