Vignir Isberg

PhD student

Elucidation of the physiological and surrogate ligands for the G protein-coupled receptor GPR139

Background
G Protein-Coupled Receptors (GPCRs) are cell-membrane signalling proteins intensively pursued due to their prominent role in human physiology and therapeutics. GPCRs can be activated by a multitude of physiological ligands (ions, small molecules, lipids, hormones, peptides, proteins) as well as sensory stimuli (odour, taste, light and pain). They constitute the most common drug target, targeted in for example allergy, asthma, psychosis, Parkinson’s disease, hyper/hypotension and cancers.

G-protein-coupled receptor 139 (GPR139) is relatively unexplored. The biological context of GPR139 is to the largest extent undefined as both the physiological ligand and function of GPR139 are unknown. The expression pattern of human and mouse GPR139 correlate with distinct areas of the CNS, including the adult caudate-putamen. To further elucidate the physiological role and therapeutic potential of the GPR139 receptor, there is a great need for identification of the endogenous agonist and the development of potent and selective pharmacological tool compounds.

Aims
The PhD project aims at significantly advancing the public knowledge about GPR139. Specifically, the project has 3 aims:

• Generate new surrogate ligands that may be used as research tools to characterize GPR139.    
• Identify the physiological ligand.
• Provide modelling input to a pharmacological PhD project to together elucidate the physiological function and therapeutic potential of targeting GPR139.

The project will benefit from collaboration with H. Lundbeck A/S via another PhD student, who will conduct the pharmacological part of the GPR139 project.

Ísberg V, Balle T, Sander T, Jørgensen FS, Gloriam DE. A G Protein- and Agonist-bound Serotonin 5-HT_2A Receptor Model Activated by Steered Molecular Dynamics Simulations. J Chem Inf Model 2011 51 (2), 315-325. doi:10.1021/ci100402f