Axel Siroy

Background

About Axel Siroy

From gene to structure! I am a biochemist focused on membrane proteins: • proteins make the workforce of the cell, they assume all the biochemical tasks essential to Life. • among them, membrane proteins (MPs) play a special part: they are the "gatekeepers", filtering the fluxes of matter and information in-and-out the cells. They play key roles in a number of diseases. • as such, the structures and functions of the MPs should be well understood of as they represent perfect drug targets (readily accessible on the cell surface) however this is not the case. MPs are difficult to study: • MPs are embedded in biological membranes made of phospholipids; they interface with the fatty acid chains by displaying a specific hydrophobic surface (the "hydrophobic belt"). • to study MPs, they first have to be solubilized out of their native membrane and into detergent micelles. • detergents are often not compatible with biochemical and biophysical assays! • additionally, detergents may disrupt the structure and hence the function of the proteins they solubilize. New tools for studying the drug targets of the future! The recent years have seen the development of new biochemical and analytical tools that allow for better and faster structural characterization of the MPs: • Nanodiscs (NDs): the structural integrity of MPs is better retained in a membrane nanodisc than in a detergent micelle • micropreparative LC (μLC): MPs usually come in smaller quantities than the soluble ones. μLC is a powerful tool to better isolate MPs. • cryo-EM: MPs seldom cristallize! Cryo-EM is the new workhorse of MP structural elucidation. • nanobodies (nAbs): small nAbs recognize structural epitopes and lock MPs in different conformations, boosting tandem structure/function studies! Through my career (see below) I have developed the skills and tools required to push the boundaries of MP research, a field that requires technical excellence, focus, stamina and open mindedness.