C06 - High-Throughput Protein Binding Assays by Microfluidic NMR

This project will develop an integrated microfluidic platform for high-throughput studies of protein binding against large libraries of ligands. This system will initially be developed for conventional, state-of-the-art NMR spectrometers, and will at a later stage be adapted to exploit the progress in compact high-field NMR systems emerging from other projects within HyPERiON. In this way, the project will form a bridge between the cutting-edge development of compact NMR systems on the one hand, and their application in life science research and drug development on the other.

Quantitative information on the interaction of proteins with small molecules, peptides, and other proteins is of fundamental importance for the understanding of biological regulation networks and for the development of drugs. Nuclear magnetic resonance spectroscopy is the most powerful technique known for obtaining such information, capable of providing not only dissociation constants, but also molecular-scale information on the binding mechanism and structure and dynamics of the bound complex. However, conventional NMR methods require large amounts of sample, manual intervention for experimental setup and calibration, as well as complex data processing. They do therefore not integrate well with modern workflows in pre-clinical drug development, which rely heavily on massively parallel and automated processing of large libraries of binding partners, protein variants, or both. The present project aims to address this by developing a fully automated experimental platform that allows extraction of high-quality NMR binding data from large libraries of protein-ligand interactions. To this effect, we will design, build, and validate a unique microfluidic system that seamlessly interfaces with high-throughput experimentation systems based on well plates.

Team