Signaling dynamics of MC4R: development of advanced treatment strategies (B02)

• Subject Area: Endocrinology, Diabetology, Metabolism ; General Genetics and Functional Genome Biology ; Biochemistry ; Biological and Biomimetic Chemistry ; Biophysics ; Pharmacology ; Cell Biology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 421152132

The melanocortin 4 receptor (MC4R) is a key regulation of body weight. In the first funding period we could demonstrate that signaling dynamics towards Gq/11 activation is the driving factor for the hyperphagia-reducing effect of the peptidic unselective MC4R ligand setmelanotide in specific groups of patients. In close cooperation with A01 (Scheerer), A07 (Meiler), B01 (Beck-Sickinger) and Z03 we aim to identify new MC4R selective and Gq/11 pathway specific ligands. In addition a human hypothalamic cell system that resemble neurons of the nucleus paraventricularis will be established by differentiation from induced pluripotent stem cells. This new human cell model will allow us to investigate MC4R signaling dynamics under physiological conditions and to test newly identify MC4R ligands.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1423: Structural Dynamics of GPCR Activation and Signaling
• Applicant Institution: Universität Leipzig
• Project Heads: Professorin Dr. Heike Biebermann; Professor Dr. Peter Kühnen