ASMENA · Functional assays for membrane protein on nanostructured supports

More than 50% of all drug targets are membrane proteins; new research tools to screen function of membrane drug targets are therefore expected to open up new avenues for original drug development. The proposed project addresses the need of the pharmaceutical industry for new technologies for reliable and efficient screening of membrane proteins as drug targets. Most critical current aspects of membrane protein assays are (a) the lack of reliable procedures to immobilize membrane proteins on sensor surfaces in a format suitable for label-free high-throughput screening of drug candidates; (b) the need for downscaling assay formats to accelerate functional screening; and (c) the feasibility of reading out the diverse functions of membrane proteins. The partners – with highly complementary expertise and experience of working together – will develop platforms for functional membrane protein assays by integration of the most recently gained knowledge and techniques. The key concepts of the platforms include (a) exploitation of nanoporous substrates to enhance the stability of supported proteolipid membranes and their integration in a sensor chip format; (b) nanoscale surface modifications for directed self-assembly of proteolipid structures on chip; and (c) self-assembly of proteolipid membranes onto nano-sized sensor structures from proteoliposomes, and demonstration of the functionality in quantitative drug candidate screening assays suitable for commercial applications. The project is expected to make a substantial contribution to (a) improved understanding of lipid membrane and membrane protein interaction with designed nanoenvironments; (b) development of prototype products and intellectual property related to membrane protein sorting and handling; (c) new compounds for functionalization of biosensor applications; (d) cost-effective array-based concepts for nanoplasmonic and electrochemical sensing; and (e) functional assays for membrane protein drug targets.