TAMPTING · The biogenesis of tail-anchored membrane proteins: knowledge and exploitation

Even in the simplest cells, the integration of proteins into a biological membrane is a complex process that is frequently coupled to ribosomal protein synthesis, and requires the coordinated actions of several additional cellular machines. The de novo recapitulation of such a complex process is well beyond the scope of our current technical abilities. Indeed, the techniques that are used to create novel proteoliposomes, for drug delivery, and artificial membranes, for synthetic biology, are extremely crude. A common approach is to mix detergent solubilised proteins with lipids, and then remove the detergent to form proteoliposomes, a process that is inefficient and difficult to control. Another major limitation of this approach is our inability to alter the protein complement of the resulting phospholipid-bilayers once they are formed. It is precisely this issue that our consortium will address, by creating a flexible and ubiquitous platform that is ideally suited to incorporating proteins into preformed liposomes. To achieve this novel and innovative breakthrough in liposome technology, we will harness the unusual ability of tail-anchored proteins to be inserted into pre-existing membranes. This technique will enable the production of customised liposomes that can be tailored to optimise drug delivery, and allow the creation of multifunctional artificial membranes for the newly emerging field of synthetic biology. The overriding ethos of our network is to develop a robust platform for the application and exploitation of tail-anchored membrane proteins based on a framework that develops and enhances fundamental insight and training in this new field of research.