Membrane Micro-Compartments

ended

More than two-thirds of all described drug targets are membrane proteins, but only for a small fraction of these hydrophobic proteins the structure is currently known. Membrane proteins are inherently challenging to produce and analyze. Consequently, in pre-clinical investigations their mechanism and drug interactions are often only derived from purified truncated parts of these proteins, taken out of their native biological context. Lacking the effects of surrounding membrane components, conclusions on drug mechanisms are indecisive. Recent advances in in situ structure determination techniques, i.e. analysis directly within the cellular environment, now have the power to overcome the limitations of classical reconstituted approaches. Complementary, we have developed a system that may facilitate structural analysis of membrane protein drug targets and has large potential for the production of native membrane proteins - an essential prerequisite for the study of membrane protein function and drug interactions. Within the scope of our proposal, we will further develop our system and transfer it into pharmaceutically relevant cell systems. Furthermore, we aim to achieve proof-of-concept and assess our system with clinically relevant membrane proteins for their suitability to solve 3D structures in complex with clinical drugs, as well as its suitability for the membrane protein production. We are convinced that our approach will have a transformative impact on how drug - membrane protein interactions can be studied, and could be exploited for drug development in the pharmaceutical industry. In the course of the project, we will establish a plan for transforming our system into a business model and commercializing our technology.