Neuroscience in Denmark

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General information

Name (center, department, group or other)
Bräuner-Osborne lab, Section for Experimental Pharmacology, Department of Drug Design and Pharmacology, University of Copenhagen
Contact name
Hans Bräuner-Osborne
Contact email
Contact title
25. January 2016

Brief description of research activities

The main focus of my group is development of state-of-the-art molecular pharmacological assays for G protein-coupled receptors and ionotropic glutamate receptors. These assays are being used to characterize ligands primarly synthesized at the Department of Drug Design and Pharmacology with special focus on subtype selectivity of the ligands and development of ligands with novel pharmacological profiles (e.g. pathway biased ligands and allosteric modulators). In this way several subtype specific/selective ligands have been identified. Another interest is ligand-receptor interactions, subtype selectivity and the activation mechanisms of receptors. These aspects have been investigated by integrated use of point-mutations, random saturation mutagenesis, chimeric receptors, engineered zinc-sites and molecular modelling.

Orphan receptors, for which the endogenous ligands remains to be identified, are also a focus area of my group. Using bioinformatics and molecular biological tools, we screen focused compound libraries for endogenous and surrogate ligands. Recently, we were the first to report the endogenous agonists for the human GPRC6A and GPR139 G-protein coupled receptors. We are currently using a GPRC6A and GPR139 knockout mouse to unravel the physiological function and therapeutic prospect of these new exciting receptors.

Most recently, my group has engaged in the use of chemogenomics and virtual screening for identification of novel pharmacological tool compounds as for example our recent discovery of the most selective GPRC6A receptor and GluN3 antagonists and GPR132 agonist reported to date.

The majority of projects are run in close collaboration with computational and medicinal chemists.


G protein-coupled receptors
NMDA receptors
Orphan receptors
Molecular pharmacology
Pharmacological tool development
Ligand and receptor mechanisms

Research tools and techniques

cell-based pharmacological assays
Corning Epic label-free assays
BRET, FRET and TR-FRET based assays
molecular biology and cloning

Scientific Personnel

No of Associate Professors/Postdocs: 5
No of PhD students: 7
Other: 2

Key references from within the last 5 years

Nørskov-Lauritsen, L., S. Jørgensen and H. Bräuner-Osborne. N-glycosylation and disulfide bonding affects GPRC6A receptor expression, function and dimerization. FEBS Lett.589: 588-597 (2015).

Clemmensen, C., S. Smajilovic, P. Wellendorph and H. Bräuner-Osborne. The GPRC6A receptor: From cloning to physiological function. Br. J. Pharmacol.171: 1129-1141 (2014).

Christiansen, B., T. Kvist, K.K. Madsen, L. Jørgensen, S.B. Vogensen, A. Schousboe, R.P. Clausen, A.A. Jensen and H. Bräuner-Osborne. Discovery of a subtype selective inhibitor of the human betaine/GABA transporter 1 (BGT-1) with a non-competitive profile. Biochem. Pharmacol. 86: 521-528 (2013).

Mølck, C., K. Harpsøe, D.E. Gloriam, R.P. Clausen, U. Madsen, L.Ø. Pedersen, H.N. Jimenez, S.M. Nielsen, J.M. Mathiesen and H. Bräuner-Osborne. Pharmacological characterization and modeling of the binding site of novel 1,3-bis(pyridinylethynyl)benzenes as metabotropic glutamate receptor 5-selective negative allosteric modulators. Mol. Pharmacol. 82: 929-937 (2012).

Absalom, N., L.F. Eghorn, I.S. Villumsen, N. Karim, T. Bay, J.V. Olsen, G.M. Knudsen, H. Bräuner-Osborne, B. Frølund, R.P. Clausen, M. Chebib and P. Wellendorph. alpha4betadelta GABA-A receptors are high-affinity targets for gamma-hydroxybutyric acid (GHB). Proc. Natl. Acad. Sci. USA. 109: 13404-13409 (2012).
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