LEGEST


Lab of GPCR Expression and Signal Transduction (LEGEST)

Department of Physiology
Faculty of Sciences
Ghent University

    

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The Laboratory of GPCR Expression and Signal Transduction (LEGEST) is headed by Prof. Dr. Kathleen Van Craenenbroeck, and is part of the Department of Physiology of the Faculty of Science at Ghent University.


The main focus of the research group is on the study of G protein-coupled receptors (GPCRs). This kind of proteins represents the single largest family of cell surface receptors engaged in signal transduction. As far as humans are concerned, it is estimated that several hundreds of distinct members of that particular protein family directly respond to a wide variety of chemical transmitters, such as biogenic amines, amino acids, peptides, lipids, nucleosides and large polypeptides. Thereby these transmembrane receptors play a key role in the regulation of biological processes. Processes that can be as diverse as, for example, neurotransmission, metabolism, cell growth, immune or inflammatory responses, olfaction and vision. Consequently, GPCRs are among the most heavily studied drug targets in the pharmaceutical industry. About half of the drugs used in clinics target these receptors directly or indirectly. Close to 50% of the drugs prescribed today actually act by activating or blocking a GPCR. In recent years increased knowledge about this kind of receptor has facilitated the screening and development of many new therapeutically active molecules. Despite major breakthroughs, our ability to fully exploit the therapeutic potential of these receptors is still limited. This is largely due to our incomplete understanding of how the signalling efficacy and selectivity are regulated in GPCR.

To contribute to improved knowledge of GPCR biology, our research group investigates the molecular mechanisms that control the efficacy and the selectivity of GPCR signalling. Thereto several projects aim at describing, on a molecular level, the link between ligand binding and signalling efficacy in specific pathways. We study regulatory processes such as receptor phosphorylation, ubiquitination and endocytosis controlling responsiveness. In addition, we analyse and try to define the role of protein-protein interactions. To that aim, various biochemical and biophysical approaches, including resonance energy transfer techniques (BRET, FRET), co-immunoprecipitation, MYTH, etc, are used. These studies already led to the insight that GPCRs can interact with each other. They form yet uninvestigated new complexes, each with its own functional properties. A better understanding of the relevance of these complexes is of paramount importance and will open new opportunities for drug development. Furthermore, this research topic gained interest from medical doctors and scientists from other academic fields because of the possible applications for diseases as fibromyalgia, morphine addiction, basal ganglia disorders (e.g. schizophrenia).

With support from the Industrial Investigation Fund of Ghent University, we also explore potential interests of pharmaceutical companies in this new area. Together we aim to translate biomedical research into high-value projects dealing with the discovery and development of more and better GPCR-targeting medicines.