Take it personal! Genetic differences in G protein-coupled receptors as studied with label-free technology

The traditional medical treatment paradigm focuses on prescribing one drug to treat all patients with a specific disease or condition, so called ‘one-size-fits-all’. However, it has been shown increasingly that differences between persons, such as in lifestyle or genes, can change both the course of a disease and effect of a drug. In order to adapt medical treatment and drug development to that, a concept know as precision medicine, it is essential to study which and how genetic differences affect drug response. This thesis describes the study of the influences of genetic variation on a specific class of drug targets, the G protein-coupled receptors (GPCRs).Altogether a novel cellular approach towards studying genetic effects on GPCR function has been explored and detailed throughout this thesis. Several GPCRs and different types of genetic variations were investigated, demonstrating together that personal cell lines in combination with label-free technology are an appropriate tool to enable GPCR pharmacogenetic studies. Incorporating aspects such as genetic variation in drug targets, representative model systems and appropriate assay technology are important factors for advancing GPCR drug discovery. The data presented in this thesis contributes towards the progress of applying precision medicine concepts to this class of drug targets.