The European Research Network on Signal Transduction (ERNEST): Toward a Multidimensional Holistic Understanding of G Protein-Coupled Receptor Signaling

Martha E Sommer; Jana Selent; Jens Carlsson; Chris De Graaf; David E Gloriam; Gyorgy M Keseru; Mickey Kosloff; Stefan Mordalski; Aurelien Rizk; Mette M Rosenkilde; Eddy Sotelo; Johanna K S Tiemann; Andrew Tobin; Nina Vardjan; Maria Waldhoer; Peter Kolb

doi:10.1021/acsptsci.0c00024

The European Research Network on Signal Transduction (ERNEST): Toward a Multidimensional Holistic Understanding of G Protein-Coupled Receptor Signaling

ACS Pharmacol Transl Sci. 2020 Mar 31;3(2):361-370. doi: 10.1021/acsptsci.0c00024. eCollection 2020 Apr 10.

Authors

Martha E Sommer^{1

2}, Jana Selent³, Jens Carlsson⁴, Chris De Graaf⁵, David E Gloriam⁶, Gyorgy M Keseru⁷, Mickey Kosloff⁸, Stefan Mordalski^{6

9}, Aurelien Rizk¹⁰, Mette M Rosenkilde¹¹, Eddy Sotelo¹², Johanna K S Tiemann^{13

14}, Andrew Tobin¹⁵, Nina Vardjan^{16

17}, Maria Waldhoer¹⁰, Peter Kolb¹⁸

Affiliations

¹ Institute of Medical Physics and Biophysics, Charité-Universitätsmedizin Berlin, Berlin, 10117, Germany.
² Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, 13125, Germany.
³ Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Medical Research Institute (IMIM) - Pompeu Fabra University (UPF), Barcelona, 08003, Spain.
⁴ Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, 752 36, Sweden.
⁵ Sosei Heptares, Cambridge, CB21 6DG, U.K.
⁶ Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, 1017, Denmark.
⁷ Medicinal Chemistry Research Group, Research Center for Natural Sciences (RCNS), Budapest, H-1117, Hungary.
⁸ Department of Human Biology, University of Haifa, Haifa, 3498838, Israel.
⁹ Department of Medicinal Chemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, 31-343, Poland.
¹⁰ InterAx Biotech AG, PARK innovAARE, Villigen, 5234, Switzerland.
¹¹ Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DK 2200, Denmark.
¹² Centro Singular de Investigación en Química Biolóxica y Materiais Moleculares (CIQUS) and Facultade de Farmacia. Universidade de Santiago de Compostela, Santiago de compostela, 15782, Spain.
¹³ Institute for Medical Physics and Biophysics, Leipzig University, Leipzig, 04109, Germany.
¹⁴ Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Kobenhavn, 2200, Denmark.
¹⁵ The Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, U.K.
¹⁶ Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, 1000, Slovenia.
¹⁷ Laboratory of Cell Engineering, Celica Biomedical, Ljubljana, 1000, Slovenia.
¹⁸ Department of Pharmaceutical Chemistry, Philipps-University Marburg, Marburg, 35039, Germany.

Abstract

G protein-coupled receptors (GPCRs) are intensively studied due to their therapeutic potential as drug targets. Members of this large family of transmembrane receptor proteins mediate signal transduction in diverse cell types and play key roles in human physiology and health. In 2013 the research consortium GLISTEN (COST Action CM1207) was founded with the goal of harnessing the substantial growth in knowledge of GPCR structure and dynamics to push forward the development of molecular modulators of GPCR function. The success of GLISTEN, coupled with new findings and paradigm shifts in the field, led in 2019 to the creation of a related consortium called ERNEST (COST Action CA18133). ERNEST broadens focus to entire signaling cascades, based on emerging ideas of how complexity and specificity in signal transduction are not determined by receptor-ligand interactions alone. A holistic approach that unites the diverse data and perspectives of the research community into a single multidimensional map holds great promise for improved drug design and therapeutic targeting.