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

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

Type: Doctoral Thesis
Title: Take it personal! Genetic differences in G protein-coupled receptors as studied with label-free technology
Author: Hillger, J.M.
Issue Date: 2017-12-07
Keywords: Precision medicine
Single Nucleotide Polymorphism
G protein-coupled receptor
Cannabinoid receptor 2
Adenosine A2A receptor
Glucose-Dependent Insulinotropic Polypeptide Receptor
Label-free cellular assay technology
xCELLigence
Lymphoblastoid cell lines
Abstract: 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.
Promotor: Supervisor: IJzerman A.P. Co-Supervisor: Heitman L.H.
Faculty: Science
University: Leiden
Uri: urn:isbn:9789463610193
Handle: http://hdl.handle.net/1887/59477
 

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application/pdf Full Text 10.94Mb Under embargo until 2019-06-07
application/pdf Cover 2.590Mb View/Open
application/pdf Title Page_Contents 857.4Kb View/Open
application/pdf Chapter 01 1.527Mb View/Open
application/pdf Chapter 02 1.387Mb View/Open Full text at publisher site
application/pdf Chapter 03 1.589Mb View/Open Full text at publisher site
application/pdf Chapter 04 1.509Mb View/Open Full text at publisher site
application/pdf Chapter 05 1.986Mb View/Open Full text at publisher site
application/pdf Chapter 06 1.799Mb Under embargo until 2019-06-07
application/pdf Chapter 07_Conclusion 1.288Mb View/Open
application/pdf Summary 134.1Kb View/Open
application/pdf Summary_in Dutch 136.2Kb View/Open
application/pdf Acknowledgements 122.3Kb View/Open
application/pdf Propositions 111.0Kb View/Open

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